Ph.D., University of Waterloo, Clinical Psychology (1981)
Current interests include social, cognitive, and biological factors in affective disorders; neural and cognitive processing of emotional stimuli and reward by depressed persons; behavioral activation and anhedonia in depression; social, emotional, and biological risk factors for depression in children.
The purpose of this study is to investigate risk factors associated with depression and how such factors might be transmitted cross-generationally. The investigators are conducting an integrative assessment of emotion regulation and stress reactivity in a group of mothers with and without a history of depression and their daughters.
Stanford is currently not accepting patients for this trial. For more information, please contact Maria Lemus, (650) 723 - 0804.
Recent research has underscored the importance of elucidating specific patterns of emotion that characterise mental disorders. We examined two emotion traits, emotional variability and emotional clarity, in relation to both categorical (diagnostic interview) and dimensional (self-report) measures of major depressive disorder (MDD) and social anxiety disorder (SAD) in women diagnosed with MDD only (n?=?35), SAD only (n?=?31), MDD and SAD (n?=?26) or no psychiatric disorder (n?=?38). Results of the categorical analyses suggest that elevated emotional variability and diminished emotional clarity are transdiagnostic of MDD and SAD. More specifically, emotional variability was elevated for MDD and SAD diagnoses compared to no diagnosis, showing an additive effect for co-occurring MDD and SAD. Similarly diminished levels of emotional clarity characterised all three clinical groups compared to the healthy control group. Dimensional findings suggest that although emotional variability is associated more consistently with depression than with social anxiety, emotional clarity is associated more consistently with social anxiety than with depression. Results are interpreted using a threshold and dose-response framework.
View details for PubMedID 26371579
Growing evidence indicates that major depressive disorder (MDD) is characterized by accelerated biological aging, including greater age-related changes in physiological functioning. The disorder is also associated with abnormal neural reward circuitry, particularly in the basal ganglia (BG). Here we assessed age-related changes in BG volume in both patients with MDD and healthy control participants.We obtained whole-brain T1-weighted images from patients with MDD and healthy controls. We estimated grey matter volumes of the BG, including the nucleus accumbens, caudate, pallidum and putamen. Volumes were assessed using multivariate analysis of covariance (MANCOVA) with age as a covariate, followed by appropriate post hoc tests.We included 232 individuals (116 patients with MDD) in our analysis. The MANCOVA yielded a significant group × age interaction (p = 0.043). Analyses for each region yielded a significant group × age interaction in the putamen (univariate test, p = 0.005; permutation test, p = 0.004); this effect was not significant in the other regions. The negative association between age and putamen volume was twice as large in the MDD than in the control group (-35.2 v. -16.7 mm3/yr), indicating greater age-related volumetric decreases in the putamen in individuals with MDD than in controls.These findings are cross-sectional; future studies should assess the longitudinal impact of accelerated aging on anhedonia and neural indices of reward processing.Our results indicate that putamen aging is accelerated in patients with MDD. Thus, the putamen may uniquely contribute to the adverse long-term effects of depressive psychopathology and may be a useful target for the treatment of MDD across the lifespan.
View details for DOI 10.1503/jpn.160010
View details for PubMedID 27749245
Major depressive disorder (MDD) often emerges during adolescence, a critical period of brain development. Recent resting-state fMRI studies of adults suggest that MDD is associated with abnormalities within and between resting-state networks (RSNs). Here we tested whether adolescent MDD is characterized by abnormalities in interactions among RSNs. Participants were 55 unmedicated adolescents diagnosed with MDD and 56 matched healthy controls. Functional connectivity was mapped using resting-state fMRI. We used the network-based statistic (NBS) to compare large-scale connectivity between groups and also compared the groups on graph metrics. We further assessed whether group differences identified using nodes defined from functionally defined RSNs were also evident when using anatomically defined nodes. In addition, we examined relations between network abnormalities and depression severity and duration. Finally, we compared intranetwork connectivity between groups and assessed the replication of previously reported MDD-related abnormalities in connectivity. The NBS indicated that, compared with controls, depressed adolescents exhibited reduced connectivity (p<0.024, corrected) between a specific set of RSNs, including components of the attention, central executive, salience, and default mode networks. The NBS did not identify group differences in network connectivity when using anatomically defined nodes. Longer duration of depression was significantly correlated with reduced connectivity in this set of network interactions (p=0.020, corrected), specifically with reduced connectivity between components of the dorsal attention network. The dorsal attention network was also characterized by reduced intranetwork connectivity in the MDD group. Finally, we replicated previously reported abnormal connectivity in individuals with MDD. In summary, adolescents with MDD show hypoconnectivity between large-scale brain networks compared with healthy controls. Given that connectivity among these networks typically increases during adolescent neurodevelopment, these results suggest that adolescent depression is associated with abnormalities in neural systems that are still developing during this critical period.
View details for DOI 10.1038/npp.2016.76
View details for Web of Science ID 000385212700017
View details for PubMedID 27238621
This study examined, for the first time, whether attentional biases can be modified in adolescents at risk for depression.The final sample consisted of 41 girls at familial risk for depression, who were randomly assigned to receive six sessions (864 trials) of real or sham attention bias training [Real attentional bias training (ABT) vs. Sham ABT]. Participants who received Real ABT completed a modified dot-probe task designed to train attention toward positive and away from negative facial expressions; in contrast, girls who received Sham ABT completed the standard dot-probe task. Attentional biases, self-reported mood, and psychophysiological responses to stress were measured at pre- and post-training assessments.As expected, girls who received Real ABT, but not those who received Sham ABT, exhibited significant increases from pre- to post-training in their attention toward happy faces and away from sad faces. Moreover, adolescents who received Real ABT were buffered against the negative outcomes experienced by adolescents who received Sham ABT. Specifically, only adolescents who received Sham ABT experienced an increase in negative mood and a pre- to post-training increase in heart rate in anticipation of the stressor.The current findings provide the first experimental evidence that attentional biases can be modified in youth at risk for depression and further suggest that ABT modulates the heightened response to stress that is otherwise experienced by high-risk adolescents.
View details for DOI 10.1111/jcpp.12587
View details for PubMedID 27390111
In the nascent field of the cognitive neuroscience of socioeconomic status (SES), researchers are using neuroimaging to examine how growing up in poverty affects children's neurocognitive development, particularly their language abilities. In this review we highlight difficulties inherent in the frequent use of reverse inference to interpret SES-related abnormalities in brain regions that support language. While there is growing evidence suggesting that SES moderates children's developing brain structure and function, no studies to date have elucidated explicitly how these neural findings are related to variations in children's language abilities, or precisely what it is about SES that underlies or contributes to these differences. This issue is complicated by the fact that SES is confounded with such linguistic factors as cultural language use, first language, and bilingualism. Thus, SES-associated differences in brain regions that support language may not necessarily indicate differences in neurocognitive abilities. In this review we consider the multidimensionality of SES, discuss studies that have found SES-related differences in structure and function in brain regions that support language, and suggest future directions for studies in the area of cognitive neuroscience of SES that are less reliant on reverse inference.
View details for DOI 10.1016/j.dcn.2016.10.001
View details for PubMedID 27744097
Affect evaluation - how people evaluate their emotion experiences - has important implications for mental health.We examined how 70 adults diagnosed with Major Depressive Disorder and/or Generalized Anxiety Disorder or no psychiatric disorders (control group) believe they should feel in the moment (should affect). We repeatedly assessed participants' current affect and should affect over one week using experience sampling. To examine the psychometric properties of should affect, participants rated their level of rumination at each survey and completed trait measures of brooding and ideal affect at the lab.Independent of group status, participants reported that they should be feeling more positive affect and less negative affect. Even after accounting for mean affect, the clinical groups' reports were generally more extreme than were those of the control group. We documented good convergent and discriminant validity of should affect. Finally, we describe clinical implications and directions for future research.
View details for DOI 10.1016/j.jad.2016.06.006
View details for PubMedID 27295379
Early life stress is associated with poorer social functioning. Attentional biases in response to threat-related cues, linked to both early experience and psychopathology, may explain this association. To date, however, no study has examined attentional biases to fearful facial expressions as a function of early life stress or examined these biases as a potential mediator of the relation between early life stress and social problems.In a sample of 154 children (ages 9-13 years) we examined the associations among interpersonal early life stressors (i.e., birth through age 6 years), attentional biases to emotional facial expressions using a dot-probe task, and social functioning on the Child Behavior Checklist.High levels of early life stress were associated with both greater levels of social problems and an attentional bias away from fearful facial expressions, even after accounting for stressors occurring in later childhood. No biases were found for happy or sad facial expressions as a function of early life stress. Finally, attentional biases to fearful faces mediated the association between early life stress and social problems.Attentional avoidance of fearful facial expressions, evidenced by a bias away from these stimuli, may be a developmental response to early adversity and link the experience of early life stress to poorer social functioning.
View details for DOI 10.1111/jcpp.12607
View details for PubMedID 27457566
Negative biases in cognition have been documented consistently in major depressive disorder (MDD), including difficulties in the ability to control the processing of negative material. Although negative information-processing biases have been studied using both behavioral and neuroimaging paradigms, relatively little research has been conducted examining the difficulties of depressed persons with inhibiting the retrieval of negative information from long-term memory. In this study, we used the think/no-think paradigm and functional magnetic resonance imaging to assess the cognitive and neural consequences of memory suppression in individuals diagnosed with depression and in healthy controls. The participants showed typical behavioral forgetting effects, but contrary to our hypotheses, there were no differences between the depressed and nondepressed participants or between neutral and negative memories. Relative to controls, depressed individuals exhibited greater activity in right middle frontal gyrus during memory suppression, regardless of the valence of the suppressed stimuli, and differential activity in the amygdala and hippocampus during memory suppression involving negatively valenced stimuli. These findings indicate that depressed individuals are characterized by neural anomalies during the suppression of long-term memories, increasing our understanding of the brain bases of negative cognitive biases in MDD.
View details for PubMedID 27649971
Although approximately half of adults diagnosed with a depressive or anxiety disorder exhibit their simultaneous co-occurrence, traditional research has centered on single-target diagnoses, overlooking comorbidities within samples. In this article, we review and extend the literature that directly investigates co-occurring depression and anxiety, with the goal of shifting the focus from co-occurring diagnoses to symptom dimensions.First, we review studies that have directly compared psychobiological features (neural, neuroendocrine, autonomic) across depression, anxiety, and their co-occurrence, defined either categorically or dimensionally. Second, we analyze adults' diurnal cortisol secretion to examine the independent and interactive relations of continuously-assessed depressive and anxiety symptoms to neuroendocrine function.Previous findings on the psychobiology of diagnostic co-occurrence are mixed. While nascent, evidence from dimensionally focused studies suggests that co-occurring levels of depressive and anxiety symptoms can interact with one another, as reflected in a distinct psychobiological profile for individuals with high levels of both symptom dimensions. Results of our analyses support this formulation: we found that depressive and anxiety symptom dimensions interacted consistently in their relation to the measures of diurnal cortisol.The illustrative sample was relatively small and included only women; future research should examine generalizability of these findings.A dimensional approach to investigating the psychobiology of co-occurring depression and anxiety affords both conceptual and practical advantages. Simultaneously assessing depressive and anxiety symptom dimensions can efficiently capture their unique, shared, and interactive features, thereby identifying targets for intervention across a wide range of symptom presentations.
View details for DOI 10.1016/j.jad.2016.08.006
View details for PubMedID 27554605
Interpersonal theories of depression postulate that depressed individuals' experience of social isolation is attributable, in part, to their tendency to behave in ways that elicit rejection from others. Depression contagion has been implicated as a factor that may account for the rejection of depressed individuals. The current study revisits this hypothesis using a controlled, but realistically motivated setting: speed-dating. Approximately two weeks before the speed-dating event, participants' depression levels were assessed. During the event, participants had four-minute "dates" with opposite-sex partners. After each date, they responded to items measuring their affect and romantic attraction. At the end of the evening, participants indicated which partners they wanted to see again. Our results did not support depression contagion: after four minutes of interaction with partners with high levels of depressive symptoms, participants did not experience increased negative affect; instead, they experienced reduced positive affect, which led to the rejection of these partners.
View details for PubMedID 27595052
Finding robust brain substrates of mood disorders is an important target for research. The degree to which major depression (MDD) and bipolar disorder (BD) are associated with common and/or distinct patterns of volumetric changes is nevertheless unclear. Furthermore, the extant literature is heterogeneous with respect to the nature of these changes. We report a meta-analysis of voxel-based morphometry (VBM) studies in MDD and BD. We identified studies published up to January 2015 that compared grey matter in MDD (50 data sets including 4101 individuals) and BD (36 data sets including 2407 individuals) using whole-brain VBM. We used statistical maps from the studies included where available and reported peak coordinates otherwise. Group comparisons and conjunction analyses identified regions in which the disorders showed common and distinct patterns of volumetric alteration. Both disorders were associated with lower grey-matter volume relative to healthy individuals in a number of areas. Conjunction analysis showed smaller volumes in both disorders in clusters in the dorsomedial and ventromedial prefrontal cortex, including the anterior cingulate cortex and bilateral insula. Group comparisons indicated that findings of smaller grey-matter volumes relative to controls in the right dorsolateral prefrontal cortex and left hippocampus, along with cerebellar, temporal and parietal regions were more substantial in major depression. These results suggest that MDD and BD are characterised by both common and distinct patterns of grey-matter volume changes. This combination of differences and similarities has the potential to inform the development of diagnostic biomarkers for these conditions.Molecular Psychiatry advance online publication, 24 May 2016; doi:10.1038/mp.2016.72.
View details for DOI 10.1038/mp.2016.72
View details for PubMedID 27217146
The habenula has been implicated in predicting negative events and in responding to unexpected negative outcomes. Animal models of depression have supported the hypothesis that perturbations in habenula activity contribute to the pathophysiology of Major Depressive Disorder (MDD), a psychiatric illness characterized by abnormalities in responding to negative feedback and by pessimism in evaluating the likelihood of future events. No research to date, however, has examined human habenula responses to potential and experienced negative outcomes in MDD. In this study, depressed and healthy control participants performed a probabilistic guessing task for monetary rewards and penalties during high-resolution functional magnetic resonance imaging of the habenula. In healthy adults, we observed a pattern of habenula activation consistent with its hypothesized role in predicting future losses and responding to suboptimal outcomes. In contrast, in depressed participants the left habenula was not activated significantly during the prediction or experience of monetary penalty. Complementing this group difference, attenuated habenula activation to negative feedback in control participants was associated with levels of shame and rumination. The results of this study suggest that depressed individuals are characterized by dysfunction in a neural system involved in generating expectations and comparing expectations with objective outcomes.
View details for DOI 10.1093/scan/nsw019
View details for Web of Science ID 000376655100016
View details for PubMedID 26884545
Little is known about the nature of the relation between information-processing biases and affective traits in bipolar disorder. The present study was designed to investigate whether attentional biases are evident in persons diagnosed with bipolar disorder when they are in a positive mood state, and whether biases are related to indices of emotion regulation and to prior history of mood episodes. Ninety adults diagnosed with bipolar I disorder and 81 controls with no lifetime mood disorder underwent a positive mood induction and then completed an emotion face dot-probe task; participants in the bipolar disorder group also completed a self-report measure of responses to positive affect. Attentional bias was not related to a diagnosis of bipolar disorder or to symptom severity. Consistent with hypotheses, analyses within the bipolar group indicated that greater dampening of positive affect related to significantly less attention paid to the positively valenced faces. Discussion focuses on the potential role of affective traits in shaping attentional bias in bipolar disorder.
View details for DOI 10.1080/02699931.2015.1014313
View details for Web of Science ID 000368723500006
View details for PubMedID 25757517
Several neuroimaging meta-analyses have summarized structural brain changes in major depression using coordinate-based methods. These methods might be biased toward brain regions where significant differences were found in the original studies. In this study, a novel voxel-based technique is implemented that estimates and meta-analyses between-group differences in grey matter from individual MRI studies, which are then applied to the study of major depression.A systematic review and meta-analysis of voxel-based morphometry studies were conducted comparing participants with major depression and healthy controls by using statistical parametric maps. Summary effect sizes were computed correcting for multiple comparisons at the voxel level. Publication bias and heterogeneity were also estimated and the excess of heterogeneity was investigated with metaregression analyses.Patients with major depression were characterized by diffuse bilateral grey matter loss in ventrolateral and ventromedial frontal systems extending into temporal gyri compared to healthy controls. Grey matter reduction was also detected in the right parahippocampal and fusiform gyri, hippocampus, and bilateral thalamus. Other areas included parietal lobes and cerebellum. There was no evidence of statistically significant publication bias or heterogeneity.The novel computational meta-analytic approach used in this study identified extensive grey matter loss in key brain regions implicated in emotion generation and regulation. Results are not biased toward the findings of the original studies because they include all available imaging data, irrespective of statistically significant regions, resulting in enhanced detection of additional areas of grey matter loss. Hum Brain Mapp 37:1393-1404, 2016. © 2016 Wiley Periodicals, Inc.
View details for DOI 10.1002/hbm.23108
View details for Web of Science ID 000372296500009
View details for PubMedID 26854015
Carver and White's (1994) Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) Scales have been useful tools for studying individual differences in reward-punishment sensitivity; however, their factor structure and invariance across development have not been well tested. In the current study, we examined the factor structure of the BIS/BAS Scales across 5 age groups: 6- to 10-year-old children (N = 229), 11- to 13-year-old early adolescents (N = 311), 14- to 16-year-old late adolescents (N = 353), 18- to 22-year-old young adults (N = 844), and 30- to 45-year-old adults (N = 471). Given poor fit of the standard 4-factor model (BIS, Reward Responsivity, Drive, Fun Seeking) in the literature, we conducted exploratory factor analyses in half of the participants and identified problematic items across age groups. The 4-factor model showed poor fit in our sample, whereas removing the BAS Fun Seeking subscale and problematic items from the remaining subscales improved fit in confirmatory factor analyses conducted with the second half of the participants. The revised model showed strict invariance across age groups and by sex, indicating consistent factor structure, item loadings, thresholds, and unique or residual variances. Additionally, in our cross-sectional data, we observed nonlinear relations between age and subscale scores, where scores tended to be higher in young adulthood than in childhood and later adulthood. Furthermore, sex differences emerged across development; adolescent and adult females had higher BIS scores than males in this age range, whereas sex differences were not observed in childhood. These differences may help us to understand the rise in internalizing psychopathology in adolescence, particularly in females. Future developmental studies are warranted to examine the impact of rewording problematic items. (PsycINFO Database Record
View details for DOI 10.1037/pas0000186
View details for PubMedID 26302106
Neural models of major depressive disorder (MDD) posit that over-response of components of the brain's salience network (SN) to negative stimuli plays a crucial role in the pathophysiology of MDD. In the present proof-of-concept study, we tested this formulation directly by examining the affective consequences of training depressed persons to down-regulate response of SN nodes to negative material. Ten participants in the real neurofeedback group saw, and attempted to learn to down-regulate, activity from an empirically identified node of the SN. Ten other participants engaged in an equivalent procedure with the exception that they saw SN-node neurofeedback indices from participants in the real neurofeedback group. Before and after scanning, all participants completed tasks assessing emotional responses to negative scenes and to negative and positive self-descriptive adjectives. Compared to participants in the sham-neurofeedback group, from pre- to post-training, participants in the real-neurofeedback group showed a greater decrease in SN-node response to negative stimuli, a greater decrease in self-reported emotional response to negative scenes, and a greater decrease in self-reported emotional response to negative self-descriptive adjectives. Our findings provide support for a neural formulation in which the SN plays a primary role in contributing to negative cognitive biases in MDD.
View details for DOI 10.1016/j.pscychresns.2016.01.016
View details for PubMedID 26862057
Generalized Anxiety Disorder (GAD) is characterized by cognitive biases toward threat-relevant information, but the underlying mechanisms are unclear. We translated a retrieval-practice paradigm from cognitive science to investigate impaired inhibition of threat information as one such mechanism. Participants diagnosed with GAD and never-disordered control participants learned a series of cue-target pairs; whereas some cues were associated only with neutral targets, others were associated with both neutral and threat targets. Next, participants practiced retrieving neutral targets, which typically suppresses the subsequent recall of unpracticed associated targets (retrieval-induced forgetting; RIF). Finally, participants were tested on their recall of all targets. Despite showing intact RIF of neutral targets, the GAD group failed to exhibit RIF of threat targets. Furthermore, within the GAD group, less RIF of threat targets correlated with greater pervasiveness of worry. Deficits in inhibitory control over threat-relevant information may underlie the cognitive pathology of GAD, which has important treatment implications.
View details for PubMedID 27042388
Previous research has emphasized the critical role of negative cognitions as a vulnerability factor in predicting depressive symptoms. Here, the authors argue that processes that function to maintain negative cognitions may serve as a catalyst for the development of depressive symptoms in the context of negative circumstances, and they suggest that poor updating of affective information in working memory is 1 such process. Thus, they posit that under high levels of stress, individuals with poor affective updating are hindered in changing the negative content in working memory associated with stressful events and, therefore, are more likely to experience increased depressive symptoms over time. To examine this hypothesis, the authors assessed affective updating ability, stress, and depressive symptoms in 200 students who were entering their first year of tertiary education. They assessed levels of depressive symptoms again both 4 months and 1 year later. Under high levels of stress, poor affective updating ability was associated with an increase in depressive symptoms at both 4 months and 1 year later. These results demonstrate that affective updating ability is an important cognitive vulnerability factor that interacts with stressful events to accelerate the development of depressive symptoms, and underscore the importance of designing early prevention or intervention approaches for individuals with this cognitive vulnerability.
View details for DOI 10.1037/emo0000097
View details for Web of Science ID 000370183800011
View details for PubMedID 26322571
Adults diagnosed with major depressive disorder (MDD) have been found to be characterized by selective attention to negative material and by impairments in their ability to disengage from, or inhibit the processing of, negative stimuli. Altered functioning in the frontal executive control network has been posited to underlie these deficits in cognitive functioning. We know little, however, about the neural underpinnings of inhibitory difficulties in depressed adolescents. We used functional magnetic resonance imaging in 18 adolescents diagnosed with MDD and 15 age- and gender-matched healthy controls (CTLs) while they performed a modified affective Go/No-Go task that was designed to measure inhibitory control in the presence of an emotional distractor. Participants were presented with either a happy or a sad face, followed by a go or a no-go target to which they either made or inhibited a motor response. A group (MDD, CTL) by valence (happy, sad) by condition (go, no-go) analysis of variance indicated that MDD adolescents showed attenuated BOLD response in the right dorsolateral prefrontal cortex (DLPFC) and in the occipital cortex bilaterally, to no-go targets that followed a sad, but not a happy, face. Adolescents diagnosed with MDD showed anomalous recruitment of prefrontal control regions during inhibition trials, suggesting depression-associated disruption in neural underpinnings of the inhibition of emotional distractors. Given that the DLPFC is associated with the maintenance of goal-relevant information, it is likely that sad faces differentially capture attention in adolescents with MDD and interfere with task demands requiring inhibition.
View details for DOI 10.1080/15374416.2014.982281
View details for Web of Science ID 000369298800003
View details for PubMedID 25635920
A growing body of research has demonstrated that having a mother with a history of major depressive disorder (MDD) is one of the strongest predictors of depression in adolescent offspring. Few studies, however, have assessed neural markers of this increased risk for depression, or examined whether risk-related anomalies in adolescents at maternal risk for depression are related to neural abnormalities in their depressed mothers. We addressed these questions by examining concordance in brain structure in two groups of participants: mothers with a history of depression and their never-depressed daughters, and never-depressed mothers and their never-depressed daughters.We scanned mothers with (remitted; RMD) and without (control; CTL) a history of recurrent episodes of depression and their never-depressed daughters, computed cortical gray matter thickness, and tested whether mothers' thickness predicted daughters' thickness.Both RMD mothers and their high-risk daughters exhibited focal areas of thinner cortical gray matter compared with their CTL/low-risk counterparts. Importantly, the extent of thickness anomalies in RMD mothers predicted analogous abnormalities in their daughters; this pattern was not present in CTL/low-risk dyads.We identified neuroanatomical risk factors that may underlie the intergenerational transmission of risk for MDD. Our findings suggest that there is concordance in brain structure in dyads that is affected by maternal depression, and that the location, direction, and extent of neural anomalies in high-risk offspring mirror those of their recurrent depressed mothers.
View details for DOI 10.1159/000444448
View details for Web of Science ID 000379162600004
View details for PubMedID 27198667
Given the increasing prevalence of Major Depressive Disorder and recent advances in preventative treatments for this disorder, an important challenge in pediatric neuroimaging is the early identification of individuals at risk for depression. We examined whether machine learning can be used to predict the onset of depression at the individual level. Thirty-three never-disordered adolescents (10-15 years old) underwent structural MRI. Participants were followed for 5 years to monitor the emergence of clinically significant depressive symptoms. We used support vector machines (SVMs) to test whether baseline cortical thickness could reliably distinguish adolescents who develop depression from adolescents who remained free of any Axis I disorder. Accuracies from subsampled cross-validated classification were used to assess classifier performance. Baseline cortical thickness correctly predicted the future onset of depression with an overall accuracy of 70% (69% sensitivity, 70% specificity; p=0.021). Examination of SVM feature weights indicated that the right medial orbitofrontal, right precentral, left anterior cingulate, and bilateral insular cortex contributed most strongly to this classification. These findings indicate that cortical gray matter structure can predict the subsequent onset of depression. An important direction for future research is to elucidate mechanisms by which these anomalies in gray matter structure increase risk for developing this disorder.
View details for DOI 10.1016/j.ijdevneu.2015.07.007
View details for Web of Science ID 000362139500018
View details for PubMedID 26315399
Rumination and worry, two forms of perseverative thinking, hold promise as core processes that transect depressive and anxiety disorders. Whereas previous studies have been limited to the laboratory or to single diagnoses, we used experience sampling methods to assess and validate rumination and worry as transdiagnostic phenomena in the daily lives of individuals diagnosed with Major Depressive Disorder (MDD), Generalized Anxiety Disorder (GAD), and co-occurring MDD-GAD. Clinical and healthy control participants carried a hand-held electronic device for one week. Eight times per day they reported on their current levels of rumination and worry and their theoretically postulated features: thought unpleasantness, repetitiveness, abstractness, uncontrollability, temporal orientation, and content, and overall senses of certainty and control. Both rumination and worry emerged as transdiagnostic processes that cut across MDD, GAD, and MDD-GAD. Furthermore, most psychological theories concerning rumination and worry strongly mapped onto participants' reports, providing the first naturalistic validation of these constructs.
View details for PubMedID 26783506
Despite its high prevalence and morbidity, the underlying neural basis of major depressive disorder (MDD) in youth is not well understood.To identify in youth diagnosed as having MDD the most reliable neural abnormalities reported in existing functional neuroimaging studies and characterize their relations with specific psychological dysfunctions.Searches were conducted in PubMed and Web of Science to identify relevant studies published from November 2006 through February 2015. The current analysis took place from August 21, 2014, to March 28, 2015.We retained articles that conducted a comparison of youth aged 4 to 24 years diagnosed as having MDD and age-matched healthy controls using task-based functional magnetic resonance imaging and a voxelwise whole-brain approach.We extracted coordinates of brain regions exhibiting differential activity in youth with MDD compared with healthy control participants. Multilevel kernel density analysis was used to examine voxelwise between-group differences throughout the whole brain. Correction for multiple comparisons was performed by computing null hypothesis distributions from 10?000 Monte Carlo simulations and calculating the cluster size necessary to obtain the familywise error rate control at P?.05.Abnormal levels of activation in youth diagnosed as having MDD compared with control participants during a variety of affective processing and executive functioning tasks.Compared with age-matched healthy control participants (n?=?274), youth with MDD (n?=?246) showed reliable patterns of abnormal activation, including the following task-general and task-specific effects: hyperactivation in subgenual anterior cingulate cortex (P?.05) and ventrolateral prefrontal cortex (P?.05) and hypoactivation in caudate (P?.01) across aggregated tasks; hyperactivation in thalamus (P?.03) and parahippocampal gyrus (P?.003) during affective processing tasks; hypoactivation in cuneus (P?.001), dorsal cingulate cortex (P?.05), and dorsal anterior insula (P?.05) during executive functioning tasks; hypoactivity in posterior insula (P?.005) during positive valence tasks; and hyperactivity in dorsolateral prefrontal cortex (P?.001) and superior temporal cortex (P?.003) during negative valence tasks.Altered activations in several distributed brain networks may help explain the following seemingly disparate symptoms of MDD in youth: hypervigilance toward emotional stimuli from the overactivation of central hubs in the subgenual anterior cingulate cortex and thalamus that lead to a cascade of other symptoms; ineffective emotion regulation despite increased activation of the dorsolateral prefrontal cortex and ventrolateral prefrontal cortex during affective processing, which may reverse across development or the clinical course; maladaptive rumination and poor executive control from difficulties shifting from default mode network activity to task-positive network activity during cognitively demanding tasks; and anhedonia from hypoactivation of the cuneus and posterior insula during reward processing.
View details for DOI 10.1001/jamapsychiatry.2015.1376
View details for Web of Science ID 000362972000017
View details for PubMedID 26332700
Behavioral inhibition (BI) is an early developing trait associated with cautiousness and development of clinical depression and anxiety. Little is known about the neural basis of BI and its predictive importance concerning risk for internalizing disorders. We looked at functional connectivity of the default-mode network (DMN) and salience network (SN), given their respective roles in self-relational and threat processing, in the risk for internalizing disorders, with an emphasis on determining the functional significance of these networks for BI.We used functional magnetic resonance imaging to scan, during the resting state, children and adolescents 8 to 17 years of age who were either at high familial risk (HR; n = 16) or low familial risk (LR; n = 18) for developing clinical depression and/or anxiety. Whole-brain DMN and SN functional connectivity were estimated for each participant and compared across groups. We also compared the LR and HR groups on levels of BI and anxiety, and incorporated these data into follow-up neurobehavioral correlation analyses.The HR group, relative to the LR group, showed significantly decreased DMN connectivity with the ventral striatum and bilateral sensorimotor cortices. Within the HR group, trait BI increased as DMN connectivity with the ventral striatum and sensorimotor cortex decreased. The HR and LR groups did not differ with respect to SN connectivity.Our findings show, in the risk for internalizing disorders, a negative functional relation between brain regions supporting self-relational processes and reward prediction. These findings represent a potential neural substrate for behavioral inhibition in the risk for clinical depression and anxiety.
View details for DOI 10.1016/j.jaac.2015.08.001
View details for PubMedID 26407494
Previous research has demonstrated that depressed individuals have difficulty both disengaging from negative information and maintaining positive information in working memory (WM). The present study was conducted to examine whether the tendency for depressed individuals to maintain negative content in WM and to experience difficulties maintaining positive content in WM is due to negative mood (in)congruency effects during a depressive episode, or whether these tendencies are evident outside of a depressive episode.Individuals who had recovered from a depressive episode and never disordered controls performed emotion 0-back and 2-back tasks designed to assess biases in updating emotional content in working memory.Similar to currently depressed individuals in previous studies, recovered depressed participants disengaged from happy stimuli more quickly and from sad stimuli more slowly than did their never-depressed counterparts.Despite the extension of a depression-specific finding to recovered depressed individuals, the present study does not test whether the identified emotion updating biases predict long-term relapse or recovery.The obtained results suggest that a decreased ability to disengage from negative content and to maintain positive content in WM represents a trait-like cognitive style that impairs adaptive emotion regulation and may contribute to the recurrent nature of depression.
View details for DOI 10.1016/j.jbtep.2015.03.009
View details for Web of Science ID 000355239600021
View details for PubMedID 25889375
Adolescence is characterized by an increase in risk-taking and reward-seeking behaviors. In other populations, increased risk taking has been associated with tighter coupling between cortisol production and ventral striatum (VS) activation during reward anticipation; this relation has not yet been examined, however, as a function of adolescent development. This study examined the influence of pubertal development on the association between diurnal cortisol production and VS activity during reward anticipation. Pre- and post-menarcheal girls collected diurnal cortisol and completed an functional magnetic resonance imaging-based monetary incentive delay task, from which we extracted estimates of VS activity during the anticipation of reward, anticipation of loss and anticipation of non-incentive neutral trials. Post-menarcheal girls showed greater coupling between the cortisol awakening response and VS activation during anticipation of reward and loss than did their pre-menarcheal counterparts. Post-menarcheal girls did not differ from pre-menarcheal girls in their cortisol-VS coupling during anticipation of neutral trials, suggesting that puberty-related changes in cortisol-VS coupling are specific to affective stimuli. Interestingly, behavioral responses during the task indicate that post-menarcheal girls are faster to engage with affective stimuli than are pre-menarcheal girls. Thus, post-menarcheal girls exhibit neurobiological and behavioral patterns that have been associated with risk taking and that may underlie the dramatic increase in risk-taking behavior documented during adolescence.
View details for DOI 10.1093/scan/nsv016
View details for Web of Science ID 000365541400011
Subcortical gray matter regions have been implicated in mood disorders, including Major Depressive Disorder (MDD) and Bipolar Disorder (BD). It is unclear, however, whether or how these regions differ among mood disorders and whether such abnormalities are state- or trait-like. In this study, we examined differences in subcortical gray matter volumes among euthymic BD, MDD, remitted MDD (RMD), and healthy (CTL) individuals. Using automated gray matter segmentation of T1-weighted MRI images, we estimated volumes of 16 major subcortical gray matter structures in 40 BD, 57 MDD, 35 RMD, and 61 CTL individuals. We used multivariate analysis of variance to examine group differences in these structures, and support vector machines (SVMs) to assess individual-by-individual classification. Analyses yielded significant group differences for caudate (p = 0.029) and ventral diencephalon (VD) volumes (p = 0.003). For the caudate, both the BD (p = 0.004) and the MDD (p = 0.037) participants had smaller volumes than did the CTL participants. For the VD, the MDD participants had larger volumes than did the BD and CTL participants (ps < 0.005). SVM distinguished MDD from BD with 59.5% accuracy. These findings indicate that mood disorders are characterized by anomalies in subcortical gray matter volumes and that the caudate and VD contribute uniquely to differential affective pathology. Identifying abnormalities in subcortical gray matter may prove useful for the prevention, diagnosis, and treatment of mood disorders.
View details for DOI 10.1016/j.jpsychires.2015.06.002
View details for Web of Science ID 000359956100015
Having a mother with major depressive disorder (MDD) is one of the strongest predictors of depression in late adolescence and early adulthood. Despite this fact, we know little about the neural mechanisms involved in the intergenerational transmission of risk for depression. Twenty-eight never-disordered daughters of recurrent depressed mothers (high-risk) and 36 never-disordered daughters of never-depressed mothers (low-risk) were scanned using MRI. Scan data were processed to provide measurements of cortical gray matter thickness. A general linear model was conducted at each surface point to assess the main effect of familial risk on cortical structure as well as to explore the interaction of familial risk and age. High-risk girls exhibited significantly thinner cortical gray matter in the right fusiform gyrus relative to low-risk girls. Exploratory analyses indicated interactions of risk group and age in the bilateral anterior insula and right anterior cingulate cortex (ACC); whereas low-risk girls exhibited an inverse association between age and thickness, girls at high risk for depression showed the reverse pattern. Additional exploratory analyses, using scores on the Children's Sadness Management Scale, indicated that thinner gray matter in the ACC of high-risk girls was associated with greater difficulty in managing sadness. These findings indicate that anomalous reductions in the cortical thickness of the fusiform gyrus may be a marker of risk for MDD. The interaction of age and group for gray matter thickness of the insula and ACC suggests a particularly important role for these regions in risk for depression and warrants additional research in longitudinal studies. (PsycINFO Database Record
View details for DOI 10.1037/abn0000050
View details for PubMedID 25894441
A growing body of research demonstrates that individuals diagnosed with major depressive disorder (MDD) are characterized by shortened telomere length, which has been posited to underlie the association between depression and increased instances of medical illness. The temporal nature of the relation between MDD and shortened telomere length, however, is not clear. Importantly, both MDD and telomere length have been associated independently with high levels of stress, implicating dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and anomalous levels of cortisol secretion in this relation. Despite these associations, no study has assessed telomere length or its relation with HPA-axis activity in individuals at risk for depression, before the onset of disorder. In the present study, we assessed cortisol levels in response to a laboratory stressor and telomere length in 97 healthy young daughters of mothers either with recurrent episodes of depression (i.e., daughters at familial risk for depression) or with no history of psychopathology. We found that daughters of depressed mothers had shorter telomeres than did daughters of never-depressed mothers and, further, that shorter telomeres were associated with greater cortisol reactivity to stress. This study is the first to demonstrate that children at familial risk of developing MDD are characterized by accelerated biological aging, operationalized as shortened telomere length, before they had experienced an onset of depression; this may predispose them to develop not only MDD but also other age-related medical illnesses. It is critical, therefore, that we attempt to identify and distinguish genetic and environmental mechanisms that contribute to telomere shortening.
View details for DOI 10.1038/mp.2014.119
View details for Web of Science ID 000353706400012
View details for PubMedID 25266121
A growing body of research is demonstrating concordance between mother and child diurnal cortisol production. In the context of maternal history of depression, intergenerational concordance of cortisol production could contribute to hypercortisolemia in children of depressed mothers, which has been shown to increase risk for MDD. The current study is the first to examine concordance in diurnal cortisol production between mothers with a history of depression and their never-depressed, but high-risk, children. We collected salivary cortisol across 2 days from mothers with (remitted; RMD) and without (CTL) a history of recurrent episodes of depression and their never-depressed daughters. As expected, RMD mothers and their daughters both exhibited higher cortisol production than did their CTL counterparts. Moreover, both across and within groups, mothers' and daughters' cortisol production were directly coupled. These findings suggest that there is an intergenerational concordance in cortisol dysregulation that may contribute to hypercortisolemia in girls at familial risk for depression.
View details for DOI 10.1016/j.biopsycho.2015.03.019
View details for Web of Science ID 000353996100011
View details for PubMedID 25862380
Both elevated and blunted levels of cortisol secretion during childhood and adolescence have been linked to the subsequent onset of major depressive disorder (MDD). These mixed findings may be due to developmental changes in HPA-axis functioning, which have not been previously assessed in the context of risk. In the present study, therefore, we examined whether pubertal development moderated the influence of cortisol secretion on the subsequent development of MDD. Eighty-nine never-disordered girls ages 9-15 years, many of whom were at high risk for depression by virtue of having a maternal history of the disorder, completed a laboratory stress task. To index cortisol reactivity, salivary cortisol samples were collected at baseline and 15min following the onset of the stressor. Girls' levels of pubertal development were measured using Tanner staging. All participants were followed through age 18 in order to assess the subsequent development of MDD. Pubertal stage moderated the effects of cortisol stress reactivity on the development of MDD. Specifically, the onset of MDD was predicted by cortisol hyporeactivity in girls who were earlier in pubertal development (Tanner stage?2), but by cortisol hyperreactivity in girls who were later in pubertal development (Tanner stage?3.5).These findings demonstrate that girls' cortisol stress reactivity predicts the subsequent onset of MDD, and further, that the nature of this effect depends on the girls' level of pubertal development. Results are discussed in the context of clarifying previous findings, and directions for future research are offered.
View details for DOI 10.1016/j.psyneuen.2015.02.004
View details for Web of Science ID 000353090100009
View details for PubMedID 25745954
Assessing neural commonalities and differences among depression, anxiety and their comorbidity is critical in developing a more integrative clinical neuroscience and in evaluating currently debated categorical vs dimensional approaches to psychiatric classification. Therefore, in this study, we sought to identify patterns of anomalous neural responding to criticism and praise that are specific to and common among major depressive disorder (MDD), social anxiety disorder (SAD) and comorbid MDD-SAD. Adult females who met formal diagnostic criteria for MDD, SAD or MDD-SAD and psychiatrically healthy participants underwent functional magnetic resonance imaging as they listened to statements directing praise or criticism at them or at another person. MDD groups showed reduced responding to praise across a distributed cortical network, an effect potentially mediated by thalamic nuclei undergirding arousal-mediated attention. SAD groups showed heightened anterior insula and decreased default-mode network response to criticism. The MDD-SAD group uniquely showed reduced responding to praise in the dorsal anterior cingulate cortex. Finally, all groups with psychopathology showed heightened response to criticism in a region of the superior frontal gyrus implicated in attentional gating. The present results suggest novel neural models of anhedonia in MDD, vigilance-withdrawal behaviors in SAD, and poorer outcome in MDD-SAD. Importantly, in identifying unique and common neural substrates of MDD and SAD, these results support a formulation in which common neural components represent general risk factors for psychopathology that, due to factors that are present at illness onset, lead to distinct forms of psychopathology with unique neural signatures.
View details for DOI 10.1093/scan/nsu084
View details for Web of Science ID 000353546800012
View details for PubMedID 25038225
Interaction between the basal ganglia and the cortex plays a critical role in a range of behaviors. Output from the basal ganglia to the cortex is thought to be relayed through the thalamus, but an intriguing alternative is that the basal ganglia may directly project to and communicate with the cortex. We explored an efferent projection from the globus pallidus externa (GPe), a key hub in the basal ganglia system, to the cortex of rats and mice. Anterograde and retrograde tracing revealed projections to the frontal premotor cortex, especially the deep projecting layers, originating from GPe neurons that receive axonal inputs from the dorsal striatum. Cre-dependent anterograde tracing in Vgat-ires-cre mice confirmed that the pallidocortical projection is GABAergic, and in vitro optogenetic stimulation in the cortex of these projections produced a fast inhibitory postsynaptic current in targeted cells that was abolished by bicuculline. The pallidocortical projections targeted GABAergic interneurons and, to a lesser extent, pyramidal neurons. This GABAergic pallidocortical pathway directly links the basal ganglia and cortex, and may play a key role in behavior and cognition in normal and disease states.
View details for DOI 10.1111/ejn.12822
View details for Web of Science ID 000351439000002
A significant proportion of military personnel deployed in support of Operation Enduring Freedom and Operation Iraqi Freedom were exposed to war-zone events associated with traumatic brain injury (TBI), depression (DEP) and posttraumatic stress disorder (PTSD). The co-occurrence of TBI, PTSD and DEP in returning Veterans has recently increased research and clinical interest. This study tested the hypothesis that white matter abnormalities are further impacted by depression. Of particular relevance is the uncinate fasciculus (UF), which is a key fronto-temporal tract involved in mood regulation, and the cingulum; a tract that connects to the hippocampus involved in memory integration. Diffusion tensor imaging (DTI) was performed on 25 patients with a combination of PTSD, TBI and DEP and 20 patients with PTSD and TBI (no DEP). Microstructural changes of white matter were found in the cingulum and UF. Fractional anisotropy (FA) was lower in Veterans with DEP compared to those without DEP.
View details for DOI 10.1016/j.biopsycho.2014.12.011
View details for PubMedID 25559772
Interpreting ambiguous stimuli in a negative manner is a core bias associated with depression. Investigators have used cognitive bias modification for interpretation (CBM-I) to demonstrate that it is possible to experimentally induce and modify these biases. This study extends previous research by examining whether CBM-I affects not only interpretation, but also memory and physiological stress response in individuals diagnosed with Major Depressive Disorder (MDD). We found that CBM-I was effective in inducing an interpretive bias. Participants also exhibited memory biases that corresponded to their training condition and demonstrated differential physiological responding in a stress task. These results suggest that interpretation biases in depression can be modified, and that this training can lead to corresponding changes in memory and to decreases in stress reactivity. Findings from this study highlight the importance of examining the relations among different cognitive biases in MDD and the possibility of modifying cognitive biases.
View details for PubMedID 25593790
Recently, there has been considerable interest in understanding brain networks in major depressive disorder (MDD). Neural pathways can be tracked in the living brain using diffusion-weighted imaging (DWI); graph theory can then be used to study properties of the resulting fiber networks. To date, global abnormalities have not been reported in tractography-based graph metrics in MDD, so we used a machine learning approach based on "support vector machines" to differentiate depressed from healthy individuals based on multiple brain network properties. We also assessed how important specific graph metrics were for this differentiation. Finally, we conducted a local graph analysis to identify abnormal connectivity at specific nodes of the network. We were able to classify depression using whole-brain graph metrics. Small-worldness was the most useful graph metric for classification. The right pars orbitalis, right inferior parietal cortex, and left rostral anterior cingulate all showed abnormal network connectivity in MDD. This is the first use of structural global graph metrics to classify depressed individuals. These findings highlight the importance of future research to understand network properties in depression across imaging modalities, improve classification results, and relate network alterations to psychiatric symptoms, medication, and comorbidities.
View details for DOI 10.3389/fpsyt.2015.00021
View details for PubMedID 25762941
Evidence is accruing that people can maintain their emotional states, but how they do it and which brain regions are responsible still remains unclear. We examined whether people maintain emotional states 'actively', with explicit elaboration of the emotion, or 'passively', without elaboration. Twenty-four participants completed an emotion maintenance task in which they either maintained the emotional intensity from the first picture of a pair to compare to that of the second picture ('maintain' condition), or only rated their emotional response to the second picture ('non-maintain' condition). Supporting the 'active' maintenance hypothesis, when maintaining vs not maintaining emotion, participants exhibited increased height and width of activation in the dorsal medial frontal cortex (MFC) and lateral prefrontal cortex, regions associated with explicit emotion generation and manipulation of contents in working memory, respectively. Supporting the 'passive' maintenance hypothesis, however, when viewing negative emotional pictures (vs neutral pictures) that were not explicitly maintained, participants exhibited greater duration of activity in the rostral MFC, a region associated with implicit emotion generation. Supported by behavioral findings, this evidence that people maintain emotional states both naturally in the rMFC and strategically in the dMFC may be critical for understanding normal as well as disordered emotion regulation.
View details for DOI 10.1093/scan/nsu011
View details for Web of Science ID 000350105900017
View details for PubMedID 24493835
Having a depressed mother is one of the strongest predictors of depression in adolescence. We investigated whether the stress of having a mother with recurrent depression is associated with dysfunction in adolescents in the HPA axis and whether the tendency to use involuntary coping strategies in dealing with this stress is associated with exacerbation of dysfunction in this system. Sixty-four never-disordered daughters of mothers with recurrent depression (high risk) and 64 never-disordered daughters of never-disordered mothers (low risk) completed diurnal cortisol and stress assessments. High-risk girls secreted more diurnal cortisol than did low-risk girls. Whereas low-risk girls secreted higher levels of cortisol with increasing stress associated with having a depressed mother, no such relation was present in high-risk girls. Finally, in contrast to low-risk girls, girls at familial risk for depression who more frequently used involuntary versus voluntary coping exhibited the greatest elevations in diurnal cortisol. These findings indicate that a tendency to utilize involuntary, as opposed to voluntary, coping strategies in dealing with stress involving maternal depression exacerbates already high levels of cortisol in youth at risk for depression. Future research that examines whether interventions aimed at increasing the use of voluntary coping strategies normalizes HPA axis dysfunction is of interest.
View details for DOI 10.1017/S0954579414001102
View details for PubMedID 25422969
Bipolar disorder (BD) has been associated with dysfunctional brain connectivity and with family chaos. It is not known whether aberrant connectivity occurs before illness onset, representing vulnerability for developing BD amidst family chaos. We used resting-state functional magnetic resonance imaging (fMRI) to examine neural network dysfunction in healthy offspring living with parents with BD and healthy comparison youth.Using two complementary methodologies [data-driven independent component analysis (ICA) and hypothesis-driven region-of-interest (ROI)-based intrinsic connectivity], we examined resting-state fMRI data in 8-17-year-old healthy offspring of a parent with BD (n = 24; high risk) and age-matched healthy youth without any personal or family psychopathology (n = 25; low risk).ICA revealed that, relative to low-risk youth, high-risk youth showed increased connectivity in the ventrolateral prefrontal cortex (VLPFC) subregion of the left executive control network (ECN), which includes frontoparietal regions important for emotion regulation. ROI-based analyses revealed that high-risk versus low-risk youth had decreased connectivities between the left amygdala and pregenual cingulate, between the subgenual cingulate and supplementary motor cortex, and between the left VLPFC and left caudate. High-risk youth showed stronger connections in the VLPFC with age and higher functioning, which may be neuroprotective, and weaker connections between the left VLPFC and caudate with more family chaos, suggesting an environmental influence on frontostriatal connectivity.Healthy offspring of parents with BD show atypical patterns of prefrontal and subcortical intrinsic connectivity that may be early markers of resilience to or vulnerability for developing BD. Longitudinal studies are needed to determine whether these patterns predict outcomes.
View details for DOI 10.1111/bdi.12221
View details for PubMedID 24938878
Bipolar disorder (BD) is highly familial and characterized by deficits in reward processing. It is not known, however, whether these deficits precede illness onset or are a consequence of the disorder.To determine whether anomalous neural processing of reward characterizes children at familial risk for BD in the absence of a personal history of a psychopathologic disorder.This study compared neural activity and behaviors of children at high and low risk for mania while they anticipate and respond to reward and loss. The study was performed from September 15, 2009, through February 17, 2012, in a university functional magnetic resonance imaging facility and included 8- to 15-year-old children without disorders born to a parent with BD (n?=?20 high-risk children) and demographically matched healthy comparison children (n?=?25 low-risk children).Neural activity, as measured with functional magnetic resonance imaging, during anticipation and receipt of reward and loss during a monetary incentive delay task.While anticipating losses, high-risk children had less activation in the pregenual cingulate than did their low-risk counterparts (t19?=?-2.44, P?=?.02). When receiving rewards, high-risk children had greater activation in the left lateral orbitofrontal cortex than did low-risk children (t43?=?-3.04, P?=?.004). High-risk children also had weaker functional connectivity between the pregenual cingulate and the right ventrolateral prefrontal cortex while anticipating rewards than did low-risk children (t19?=?-4.38, P?.001) but had a stronger connectivity between these regions while anticipating losses (t24?=?2.76, P?=?.01). Finally, in high- but not low-risk children, novelty seeking was associated with increased striatal and amygdalar activation in the anticipation of losses, and impulsivity was associated with increased striatal and insula activation in the receipt of rewards.Aberrant prefrontal activations and connectivities during reward processing suggest mechanisms that underlie early vulnerabilities for developing dysfunctional regulation of goal pursuit and motivation in children at high risk for mania. Longitudinal studies are needed to examine whether these patterns of neural activation predict the onset of mania and other mood disorders in high-risk children.
View details for DOI 10.1001/jamapsychiatry.2014.1031
View details for PubMedID 25142103
Major depressive disorder (MDD) is a recurrent mood disorder. The high rate of recurrence of MDD suggests the presence of stable vulnerability factors that place individuals with a history of major depression at an increased risk for the onset of another episode. Previous research has linked the remitted state, and therefore increased vulnerability for depressive relapse, with difficulties in the use of pleasant autobiographical memories to repair sad mood. In the present study, we examined the neural correlates of these difficulties. Groups of 16 currently euthymic, remitted depressed individuals and 16 healthy (control) women underwent functional magnetic resonance imaging (fMRI) during sad mood induction and during recovery from a sad mood state through recall of mood-incongruent positive autobiographical memories. Sad mood was induced in participants by using film clips; participants then recalled positive autobiographical memories, a procedure previously shown to repair negative affect. During both the sad mood induction and automatic mood regulation, control participants exhibited activation in the left ventrolateral prefrontal cortex (vlPFC) and cuneus; in contrast, remitted participants exhibited a decrease in activation in these regions. Furthermore, exploratory analyses revealed that reduced activation levels during mood regulation predicted a worsening of depressive symptoms at a 20-month follow-up assessment. These findings highlight a dynamic role of the vlPFC and cuneus in the experience and modulation of emotional states and suggest that functional anomalies of these brain regions are associated with a history of, and vulnerability to, depression.
View details for DOI 10.3758/s13415-013-0216-0
View details for PubMedID 24146315
Diffusion-weighted imaging allows for in vivo assessment of white matter structure, which can be used to assess aberrations associated with disease. Several new methods permit the automated assessment of important white matter characteristics. In the current study we used Automated Fiber Quantification (AFQ) to assess differences between depressed and nondepressed individuals in 18 major white matter tracts. We then used the Maximum Density Path (MDP) method to further characterize group differences identified with AFQ. The results of the AFQ analyses indicated that fractional anisotropy (FA; an index of white matter integrity) along bilateral corticospinal tracts (CST) was higher in depressed than in nondepressed individuals. MDP analyses revealed that white matter anomalies were restricted to four subregions that included the corona radiata and the internal and external capsules. These results provide further evidence that MDD is associated with abnormalities in cortical-to-subcortical connectivity.
View details for PubMedID 25540677
Daughters of depressed mothers are at increased risk for developing a depressive disorder. We know relatively little, however, about the specific factors that contribute to this elevated risk. The present study investigated the effects of familial risk for depression and the 5-HTTLPR and COMT Val158Met polymorphisms, which have been associated with risk for depression, on biases in endorsement of and memory for positive and negative adjectives.Following a negative mood induction, 60 girls between the ages of 10 and 14 who had recurrent depressed mothers (high risk for depression) and 91 age-matched daughters of never-disordered mothers (low risk for depression) completed a Self-Referent Encoding Task in which they decided whether negative and positive adjectives described them. Following the task they were asked to recall as many of the adjectives as they could.Despite the absence of significant group differences in endorsement of positive or negative adjectives, high-risk girls with the COMT Val158Met Val/Val polymorphism recalled more positive (but not negative) words that they had endorsed than did high-risk girls who were homozygous for the Met allele. COMT was not associated with recall of valenced adjectives in low-risk girls. Across risk groups, 5-HTTLPR polymorphism was not associated with recall of valenced adjectives.Even with over 150 participants, there were relatively small numbers in some of the cells of this study, limiting its statistical power.These results suggest that assessing the interaction of familial risk status and COMT polymorphism is important in understanding the development of depressive disorders.
View details for DOI 10.1016/j.jad.2014.02.020
View details for Web of Science ID 000333398400011
View details for PubMedID 24679392
The occurrence of concordance among different response components during an emotional episode is a key feature of several contemporary accounts and definitions of emotion. Yet, capturing such response concordance in empirical data has proven to be elusive, in large part because of a lack of appropriate statistical tools that are tailored to measure the intricacies of response concordance in the context of data on emotional responding. In this article, we present a tool we developed to detect two different forms of response concordance-response patterning and synchronization-in multivariate time series data of emotional responding, and apply this tool to data concerning physiological responding to emotional stimuli. While the findings provide partial evidence for both response patterning and synchronization, they also show that the presence and nature of such patterning and synchronization is strongly person-dependent.
View details for DOI 10.1016/j.biopsycho.2013.10.011
View details for Web of Science ID 000335499900004
View details for PubMedID 24220647
Graph theory is increasingly used in the field of neuroscience to understand the large-scale network structure of the human brain. There is also considerable interest in applying machine learning techniques in clinical settings, for example, to make diagnoses or predict treatment outcomes. Here we used support-vector machines (SVMs), in conjunction with whole-brain tractography, to identify graph metrics that best differentiate individuals with Major Depressive Disorder (MDD) from nondepressed controls. To do this, we applied a novel feature-scoring procedure that incorporates iterative classifier performance to assess feature robustness. We found that small-worldness, a measure of the balance between global integration and local specialization, most reliably differentiated MDD from nondepressed individuals. Post-hoc regional analyses suggested that heightened connectivity of the subcallosal cingulate gyrus (SCG) in MDDs contributes to these differences. The current study provides a novel way to assess the robustness of classification features and reveals anomalies in large-scale neural networks in MDD.
View details for PubMedID 25580184
Considerable research indicates that depressed individuals have better memory for negative material than do nondepressed individuals, and that this bias is associated with differential patterns of neural activation. It is not known, however, whether these aberrant activation patterns predict illness course. Using functional neuroimaging, we examined whether change in depressive symptoms is predicted by baseline patterns of neural activation that underlie negative memory biases in major depressive disorder. Depressed participants viewed negative and neutral pictures during functional MRI at baseline and completed an incidental memory task for these pictures 1 week later. Depression severity was assessed by administering the Beck Depression Inventory both at baseline (Time 1) and at Time 2, an average of 18 months later. Contrast maps of activation for subsequently remembered negative versus subsequently remembered neutral pictures were regressed against change in Beck Depression Inventory scores between Time 1 and Time 2, controlling for initial symptom severity. Results from this analysis revealed no associations between memory sensitivity for negative stimuli and symptom change. In contrast, whole brain analyses revealed significant positive associations between within-subject changes in depressive symptoms and baseline neural activation to successfully recalled negative pictures in the posterior cingulate cortex and medial prefrontal cortex. These findings indicate that neural activation in cortical midline regions is a better predictor of long-term symptomatic outcome than is memory sensitivity for negative material.
View details for DOI 10.1097/WNR.0000000000000095
View details for Web of Science ID 000332601600009
Insomnia is among the most prevalent and costly of all sleep-related disorders. To characterize the neural mechanisms underlying subjective dysfunction in insomnia, we examined brain activity in 17 female insomniacs and 17 female healthy controls using simultaneous functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) while they were resting and while they were trying to fall asleep. In examining the dynamic regional activity within intrinsic brain networks, we found that, compared with controls, insomniacs had greater involvement of the anterior insula with salience networks, as well as insula BOLD correlation with EEG gamma frequency power during rest in insomniacs. This increased involvement of the anterior insula was associated with negative affect in insomniacs. Aberrant activation of the insula, which integrates temporal and bodily states, in arousal networks may underlie the misperception of sleep quality and subjective distress in insomnia.
View details for DOI 10.1016/j.biopsycho.2013.12.016
View details for Web of Science ID 000333060000001
Three of the most consistently reported and powerful predictors of depression are a recent major life event, a positive family history for depression, and a personal history of past depressive episodes. Little research, however, has evaluated the inter-relations among these predictors in depressed samples. Such information is descriptively valuable and potentially etiologically informative. In the present article we summarize the existing literature and test four predictions in a sample of 62 clinically depressed individuals: (1) participants who experienced a major life event prior to onset would be less likely than participants who did not experience a major life event to have a positive family history for depression; (2) participants with a recent major life event would have fewer lifetime episodes of depression than would participants without; (3) participants with a positive family history for depression would have more lifetime episodes of depression than would participants with a negative family history for depression; and (4) we would obtain a 3-way interaction in which participants with a positive family history and without a major life event would have the most lifetime episodes, whereas participants with a negative family history and a major life event would have the fewest lifetime episodes. The first three predictions were confirmed, and the fourth prediction partially confirmed. These novel findings begin to elucidate the complex relations among these three prominent risk factors for depression, and point to avenues of research that may help illuminate the origins of depressive episodes.
View details for DOI 10.1016/j.jpsychires.2013.11.005
View details for Web of Science ID 000329772800013
View details for PubMedID 24308926
Bipolar disorder has been associated with elevated impulsivity - a complex construct subsuming multiple facets. We aimed to compare specific facets of impulsivity in bipolar disorder, including those related to key psychological correlates of the illness: reward sensitivity and strong emotion.Ninety-one individuals diagnosed with bipolar I disorder (inter-episode period) and 80 controls completed several well-validated impulsivity measures, including those relevant to reward (Fun-seeking subscale of the Behavioral Activation System scale) and emotion (Positive Urgency and Negative Urgency scales).Bipolar participants reported higher impulsivity scores than did controls on all of the impulsivity measures, except the Fun-seeking subscale of the Behavioral Activation System scale. Positive Urgency - a measure assessing the tendency to act impulsively when experiencing strong positive emotion - yielded the largest group differences: F(1,170) = 78.69, P < 0.001, partial ?(2) = 0.316. Positive Urgency was also associated with poorer psychosocial functioning in the bipolar group: ?R(2) = 0.24, b = -0.45, P < 0.001.Individuals with bipolar I disorder appear to be at particular risk of behaving impulsively when experiencing strong positive emotions. Findings provide an important first step toward developing a more refined understanding of impulsivity in bipolar disorder with the potential to inform targeted interventions.
View details for DOI 10.1111/acps.12136
View details for Web of Science ID 000346660600003
Scientists are beginning to document abnormalities in white matter connectivity in major depressive disorder (MDD). Recent developments in diffusion-weighted image analyses, including tractography clustering methods, may yield improved characterization of these white matter abnormalities in MDD. In this study, we acquired diffusion-weighted imaging data from MDD participants and matched healthy controls. We analyzed these data using two tractography clustering methods: automated fiber quantification (AFQ) and the maximum density path (MDP) procedure. We used AFQ to compare fractional anisotropy (FA; an index of water diffusion) in these two groups across major white matter tracts. Subsequently, we used the MDP procedure to compare FA differences in fiber paths related to the abnormalities in major fiber tracts that were identified using AFQ.FA was higher in the bilateral corticospinal tracts (CSTs) in MDD (p's?0.002). Secondary analyses using the MDP procedure detected primarily increases in FA in the CST-related fiber paths of the bilateral posterior limbs of the internal capsule, right superior corona radiata, and the left external capsule.This is the first study to implicate the CST and several related fiber pathways in MDD. These findings suggest important new hypotheses regarding the role of CST abnormalities in MDD, including in relation to explicating CST-related abnormalities to depressive symptoms and RDoC domains and constructs.
View details for DOI 10.1186/2045-5380-4-8
View details for PubMedID 25295159
Major depressive disorder (MDD) is associated with biases in memory, including poor memory for positive stimuli. It is unclear, however, if this impaired memory for positive stimuli in MDD is related to difficulties in the initial processing of stimuli, or alternatively, reflects a decreased ability to draw on memories of positive stimuli after they have been formed. Using two versions of a word-matching task that featured a mixture of novel and practiced emotionally valenced words, we found that depressed individuals experienced greater difficulty learning positively valenced information than did their nondepressed peers. This difficulty seemed to be specific to initial encounters with the novel, but not the practiced, positive stimuli. These findings suggest that memory deficits for positive information associated with depression are related to how this information is initially processed. Implications of these findings for interventions are discussed and directions for future research are advanced.
View details for DOI 10.1080/02699931.2013.866936
View details for PubMedID 24382137
BACKGROUND: Major depressive disorder (MDD) is characterized by abnormalities in structure, function, and connectivity in several brain regions. Few studies have examined how these regions are organized in the brain or investigated network-level structural aberrations that might be associated with depression. METHODS: We used graph analysis to examine the gray matter structural networks of individuals diagnosed with MDD (n = 93) and a demographically similar healthy comparison group (n = 151) with no history of psychopathology. The efficiency of structural networks for processing information was determined by quantifying local interconnectivity (clustering) and global integration (path length). We also compared the groups on the contributions of high-degree nodes (i.e., hubs) and regional network measures, including degree (number of connections in a node) and betweenness (fraction of short path connections in a node). RESULTS: Depressed participants had significantly decreased clustering in their brain networks across a range of network densities. Compared with control subjects, depressed participants had fewer hubs primarily in medial frontal and medial temporal areas, had higher degree in the left supramarginal gyrus and right gyrus rectus, and had higher betweenness in the right amygdala and left medial orbitofrontal gyrus. CONCLUSIONS: Networks of depressed individuals are characterized by a less efficient organization involving decreased regional connectivity compared with control subjects. Regional connections in the amygdala and medial prefrontal cortex may play a role in maintaining or adapting to depressive pathology. This is the first report of anomalous large-scale gray matter structural networks in MDD and provides new insights concerning the neurobiological mechanisms associated with this disorder.
View details for DOI 10.1016/j.biopsych.2013.03.005
View details for PubMedID 23601854
Little work has examined the relation between interoceptive awareness and symptoms of Major Depressive Disorder (MDD). Existing research suggests that depressed individuals exhibit impaired heartbeat perception, though the results of this research have been equivocal. Importantly, depressed participants in these studies have had comorbid anxiety disorders, making it difficult to draw inferences about interoceptive awareness in MDD. The current study addresses this issue by assessing heartbeat perception in depressed women without current anxiety disorders and exploring the relation between interoception and perturbations in both affective intensity and decision making, components of MDD postulated to be related to bodily awareness.Depressed women without concurrent anxiety disorders (n=25) and never-disordered controls (n=36) performed a heartbeat perception task. Participants completed the self-report Affect Intensity Measure (AIM), and decision-making difficulty was assessed in MDD participants using the Structured Clinical Interview for DSM-IV.Depressed women exhibited poorer heartbeat perception accuracy than did control participants. Impaired accuracy in MDD participants was associated with reduced positive affectivity and difficulty in decision making.Our sample was composed exclusively of females and was heterogeneous with respect to treatment status, thereby limiting our ability to generalize results to depressed males and to exclude the contribution of exogenous factors to the observed group differences.Results of this study suggest that for depressed individuals without anxiety comorbidities, disrupted perception of bodily responses reduces both the experience of positive arousal and the ability to use interoceptive feedback to inform decision making.
View details for DOI 10.1016/j.jad.2013.06.044
View details for Web of Science ID 000325432900052
View details for PubMedID 23972662
Unaffected relatives (URs) of individuals with major depressive disorder (MDD) are biologically more vulnerable to depression. We compare healthy URs and controls at the level of phenotype (symptoms and functioning) and endophenotype (negative emotion bias), and further investigate the interrelation between these and the contribution of environmental early life stress.URs (n=101), identified using Family History Screen interview methods and matched controls completed written and interview questions assessing symptoms of depression and anxiety, negative cognitive style, life functioning and early life stress. Biases in emotion processing were measured using a facial expression of emotion identification paradigm.Compared to controls, URs reported higher levels of depression and anxiety, a stronger negative cognitive bias, and poorer functioning and lower satisfaction with life. URs were slower to correctly identify fear and sad facial expressions. A slower response time to identify sad faces was correlated with lower quality of life in the social domain. Early life stress (ELS) did not contribute significantly to any outcome.The methodology relies on accurate reporting of participants' own psychiatric history and that of their family members. The degree of vulnerability varies among URs.A family history of depression accounts for subtle differences in symptom levels and functioning without a necessary role of ELS. A negative emotion bias in processing emotion may be one vulnerability marker for MDD. Biological markers may affect functioning measures before symptoms at the level of experience.
View details for DOI 10.1016/j.jad.2013.04.042
View details for Web of Science ID 000323563300043
View details for PubMedID 23764382
BACKGROUND: Previous research has implicated the behavioral activation system (BAS) in depression. The relationship of BAS functioning to aspects of cognitive vulnerability to depression, however, is not known. Method The present study investigated associations among level of BAS functioning and the encoding and recall of positive and negative self-referent information in currently non-depressed participants with a history of recurrent major depression (recovered; RMD) and in never-depressed control participants (CTL). Participants completed self-report measures of levels of BAS and behavioral inhibition system (BIS) functioning. Following a negative mood induction, participants were presented with a series of positive and negative adjectives; they indicated which words described them and later recalled as many of the words as they were able. RESULTS: The relationship of BAS functioning to self-referent processing was dependent on participant group. Although lower BAS reward responsivity was associated with the endorsement and recall of fewer positive words across groups, the magnitude of these associations was stronger, and was only significant, within the RMD group. Furthermore, only for RMD participants was lower BAS reward responsivity associated with the endorsement of more negative words. These effects were not accounted for by depressive or anxiety symptoms, current mood, or level of BIS functioning. CONCLUSIONS: These results indicate that BAS functioning may be distinctively linked to negatively biased self-referent processing, one facet of cognitive vulnerability to depression, in individuals with a history of major depressive disorder. Enhancing BAS functioning may be important in buffering cognitive vulnerability to depression.
View details for DOI 10.1017/S0033291712002851
View details for Web of Science ID 000322828600011
View details for PubMedID 23298796
Rumination, defined as repetitive thinking about negative information, has been found to lead to serious maladaptive consequences, including longer and more severe episodes of major depression. In this review, we present and discuss research findings motivated by the formulation that individual differences in cognitive processes that control how information is processed influence the likelihood that thoughts will become repetitive and negative. Several studies have demonstrated that a tendency to ruminate (i.e., trait rumination) is related to difficulties updating working memory (WM) and disengaging from and forgetting no-longer-relevant information. Other investigators have documented that trait rumination is also associated with an enhanced ability to ignore distracting information and with more stable maintenance of task-relevant information. In contrast to trait rumination, a state of rumination has been found to be related to widespread deficits in cognitive control. In this article, we discuss how the current accounts of control functioning cannot explain this pattern of anomalous control functioning. To explain these findings, including unexpected and contradictory results, we present an attentional scope model of rumination that posits that a constricted array of thoughts, percepts, and actions that are activated in WM or available for selection from long-term memory affects the control functioning of trait ruminators. This model explains, at a cognitive level, why rumination is particularly likely to arise when individuals are in a negative mood state; it also accounts for a number of findings outside of the rumination-control literature and generates several novel predictions.
View details for DOI 10.1037/a0030923
View details for Web of Science ID 000323688000008
View details for PubMedID 23244316
View details for Web of Science ID 000318671800677
Researchers have linked bipolar disorder to elevations in reward sensitivity and positive affect. Little is known, however, about how people with bipolar disorder respond to rewards and positive affect and how these tendencies relate to functioning or quality of life.Persons diagnosed with bipolar I disorder and matched controls completed the Responses to Positive Affect (RPA) measure and the Brief Quality of Life in Bipolar Disorder scale. Bipolar participants also completed the Reward Responses Inventory, which we designed to assess the extent to which participants avoid rewarding activities to prevent mania. A subsample of participants with bipolar disorder completed a positive mood induction procedure to examine the validity of the Response to Positive Affect scale.The majority of bipolar participants reported avoiding at least one rewarding activity as a means of preventing mania. In addition, people with bipolar I disorder reported more dampening responses to positive affect than did control participants. Dampening positive emotions was related to lower quality of life.This study does not address whether responses to affect and reward are related to the longitudinal course of symptoms.These findings suggest that people with bipolar I disorder seem to be aware of the potential of goal achievements to trigger mania, and many people with bipolar disorder seem to take steps to avoid positive emotion and reward.
View details for DOI 10.1016/j.jad.2012.07.027
View details for Web of Science ID 000315580700015
View details for PubMedID 23021378
Recent research detailing the intrinsic functional organization of the brain provides a unique and useful framework to gain a better understanding of the neural bases of Major Depressive Disorder (MDD). In this review, we first present a brief history of neuroimaging research that has increased our understanding of the functional macro-architecture of the brain. From this macro-architectural perspective, we examine the extant body of functional neuroimaging research assessing MDD with a specific emphasis on the contributions of default-mode, executive, and salience networks in this debilitating disorder. Next, we describe recent investigations conducted in our laboratory in which we explicitly adopt a neural-system perspective in examining the relations among these networks in MDD. Finally, we offer directions for future research that we believe will facilitate the development of more detailed and integrative models of neural dysfunction in depression.
View details for DOI 10.1016/j.nbd.2012.01.015
View details for Web of Science ID 000315430000002
View details for PubMedID 23477309
Recurrent uncontrollable negative thoughts are a hallmark of depressive episodes. Deficits in cognitive control have been proposed to underlie this debilitating aspect of depression. Here, we used functional neuroimaging during an emotional working memory (WM) task to elucidate the neural correlates of these difficulties in cognitive control. In a WM manipulation involving depressed participants, the dorsal anterior cingulate and parietal and bilateral insular cortices were activated significantly more when negative words were removed from WM than when they were maintained in WM; in contrast, nondepressed participants exhibited stronger neural activations in these regions for positive than for negative material. These findings implicate anomalous activation of components of the task-positive network, known to be modulated by cognitive effort, in depression-associated difficulties in expelling negative material from WM. Future studies should examine the association between these aberrations and the maintenance of depressive symptoms.
View details for DOI 10.1177/0956797612457380
View details for Web of Science ID 000316640900014
Identifying factors that may protect individuals from developing Major Depressive Disorder (MDD) in the face of stress is critical. In the current study we experimentally tested whether such a potentially protective factor, engaging in acute exercise, reduces the adverse effects of repeated sad mood inductions in individuals who have recovered from depression. We hypothesized that recovered depressed participants who engage in acute exercise report a smaller increase in negative affect (NA) and a smaller decrease in positive affect (PA) when exposed to a repeated sad mood induction (i.e., habituation), whereas participants who do not exercise show sensitization (i.e., increased NA and decreased PA in response to a repeated adverse stimulus). Forty-one women recovered from MDD and 40 healthy control women were randomly assigned to either exercise for 15 minutes or quiet rest. Afterward, participants were exposed to two sad mood inductions and reported their levels of affect throughout the study. Recovered depressed participants who had not exercised exhibited higher NA after the second sad mood induction, a finding consistent with sensitization. In contrast, both recovered depressed participants who had engaged in acute exercise and healthy control participants showed no increase in NA in response to the repeated sad mood induction. Participants who exercised reported higher PA after the exercise bout; however, our hypothesis concerning reported PA trajectories following the sad mood inductions was not supported. Results suggest that exercise can serve as a protective factor in the face of exposure to repeated emotional stressors, particularly concerning NA in individuals who have recovered from depression.
View details for DOI 10.1037/a0029881
View details for Web of Science ID 000314641500007
View details for PubMedID 22985013
Major depression is associated with a wide range of neurobiological disturbances, including anomalies in the structure and function of cortical and subcortical gray matter and dysregulation of the HPA axis. In this chapter, we review research demonstrating that many of these abnormalities are also present in never-depressed offspring of adults with recurrent depression and discuss how such findings might reflect dysfunctional neuroregulatory systems that precede the onset of this disorder. We also briefly discuss candidate genes and environmental factors that have been posited to be directly involved in the transmission of neural and HPA-axis abnormalities from depressed parents to their offspring, and we review how, by obtaining a better understanding of the neurobiological markers of depression risk, we can facilitate the development of targeted strategies for the prevention and treatment of major depression.
View details for DOI 10.1007/7854_2012_213
View details for PubMedID 22573472
The ability to delay gratification in childhood has been linked to positive outcomes in adolescence and adulthood. Here we examine a subsample of participants from a seminal longitudinal study of self-control throughout a subject's life span. Self-control, first studied in children at age 4 years, is now re-examined 40 years later, on a task that required control over the contents of working memory. We examine whether patterns of brain activation on this task can reliably distinguish participants with consistently low and high self-control abilities (low versus high delayers). We find that low delayers recruit significantly higher-dimensional neural networks when performing the task compared with high delayers. High delayers are also more homogeneous as a group in their neural patterns compared with low delayers. From these brain patterns, we can predict with 71% accuracy, whether a participant is a high or low delayer. The present results suggest that dimensionality of neural networks is a biological predictor of self-control abilities.
View details for DOI 10.1038/ncomms2374
View details for Web of Science ID 000316614600043
View details for PubMedID 23340413
Bipolar disorder (BD) is a debilitating psychiatric condition that commonly begins in adolescence, a developmental period that has been associated with increased reward seeking. Because youth with BD are especially vulnerable to negative risk-taking behaviors, understanding the neural mechanisms by which dysregulated affect interacts with the neurobehavioral processing of reward is clearly important. One way to clarify how manic symptoms evolve in BD is to "prime" the affect before presenting rewarding stimuli. The objective of this study was to investigate the neural effects of an affective priming task designed to positively induce mood before reward processing in adolescents with and without BD.Neural activity and behaviors during the anticipation of and response to monetary reward and loss after an affective prime were compared using functional magnetic resonance imaging in 13- to 18-year-old adolescents with a recent onset of BD-I (n = 24) and demographically matched healthy comparison youth (n = 24).Compared with the healthy control youth, youth with BD had speeded reaction times and showed decreased activation in the thalamus and inferior temporal gyrus while anticipating gains after priming but increased activations in the middle frontal gyrus and parietal cortices while anticipating losses after priming. Youth with BD also showed less activation in the inferior parietal lobule, thalamus, and superior frontal gyrus while receiving losses after priming.Aberrant prefrontal and subcortical activations during reward processing suggest mechanisms that may underlie disordered self-awareness during goal pursuit and motivation in BD. Longitudinal studies are needed to examine whether this pattern of neural activation predicts a poorer long-term outcome.
View details for DOI 10.1016/j.jaac.2012.10.004
View details for Web of Science ID 000313143400008
Major Depressive Disorder (MDD) is characterized by several emotional disturbances. One possible but not well-examined disturbance is in attention to emotion, an important facet of emotional awareness. We examined whether attention to emotion predicted recovery from MDD. Fifty-three adults with current MDD completed a week of experience sampling (Time 1). At each prompt, participants reported attention to emotion, negative affect (NA), and positive affect (PA). Approximately one year later (Time 2), the depressive status of 27 participants was reassessed. Participants who had recovered from MDD (n = 8) indicated paying less attention to their emotions at Time 1 than did participants who had not fully recovered (n = 19). Attention to emotion was better predictor of recovery than was severity of MDD, NA, or PA at Time 1. Levels of attention to emotion at Time 1 in participants who recovered from MDD did not differ significantly from the levels reported by 53 never-depressed individuals who had participated in the experience sampling. Findings indicate that high levels of an otherwise adaptive emotional facet can adversely affect the course of MDD.
View details for DOI 10.1155/2013/540726
View details for PubMedID 23853719
Depressed individuals who ruminate have difficulties learning from punishment and suppressing task-irrelevant information. The C957T polymorphism of the DRD2 gene, which affects functioning of D2 dopamine receptors (DRD2) that are expressed predominantly in the indirect pathway of the basal ganglia, has been found to influence suppression and punishment learning. Given these associations, we examined in the present study whether depressive rumination is related to the C957T polymorphism in 317 clinically depressed individuals and 317 never-depressed control individuals. A 2 × 2 (diagnostic group ×C957T polymorphism) analysis of variance conducted on depressive rumination scores yielded a significant interaction of group and C957T: Individuals with two 957C alleles reported higher levels of depressive rumination than did individuals with one or two 957T alleles if they were depressed, but not if they were healthy. The present findings suggest that the dopaminergic system and DRD2 are related to the frequency of maladaptive rumination in depressed individuals. Thus, DRD2 may be an important target for the pharmacological treatment of depressive rumination.
View details for DOI 10.3758/s13415-012-0112-z
View details for Web of Science ID 000311498900010
View details for PubMedID 22864973
Investigators have begun to examine the temporal dynamics of affect in individuals diagnosed with major depressive disorder (MDD), focusing on instability, inertia, and reactivity of emotion. How these dynamics differ between individuals with MDD and healthy controls have not before been examined in a single study. In this study, 53 adults with MDD and 53 healthy adults carried hand-held electronic devices for approximately 7 days and were prompted randomly 8 times per day to report their levels of current negative affect (NA), positive affect (PA), and the occurrence of significant events. In terms of NA, compared with healthy controls, depressed participants reported greater instability and greater reactivity to positive events, but comparable levels of inertia and reactivity to negative events. Neither average levels of NA nor NA reactivity to, frequency or intensity of, events accounted for the group difference in instability of NA. In terms of PA, the MDD and control groups did not differ significantly in their instability, inertia, or reactivity to positive or negative events. These findings highlight the importance of emotional instability in MDD, particularly with respect to NA, and contribute to a more nuanced understanding of the everyday emotional experiences of depressed individuals.
View details for DOI 10.1037/a0027978
View details for Web of Science ID 000311527700003
View details for PubMedID 22708886
This study aimed to explore whether walking in nature may be beneficial for individuals with major depressive disorder (MDD). Healthy adults demonstrate significant cognitive gains after nature walks, but it was unclear whether those same benefits would be achieved in a depressed sample as walking alone in nature might induce rumination, thereby worsening memory and mood.Twenty individuals diagnosed with MDD participated in this study. At baseline, mood and short term memory span were assessed using the PANAS and the backwards digit span (BDS) task, respectively. Participants were then asked to think about an unresolved negative autobiographical event to prime rumination, prior to taking a 50-min walk in either a natural or urban setting. After the walk, mood and short-term memory span were reassessed. The following week, participants returned to the lab and repeated the entire procedure, but walked in the location not visited in the first session (i.e., a counterbalanced within-subjects design).Participants exhibited significant increases in memory span after the nature walk relative to the urban walk, p<.001, ?(p)(2)=.53 (a large effect-size). Participants also showed increases in mood, but the mood effects did not correlate with the memory effects, suggesting separable mechanisms and replicating previous work.Sample size and participants' motivation.These findings extend earlier work demonstrating the cognitive and affective benefits of interacting with nature to individuals with MDD. Therefore, interacting with nature may be useful clinically as a supplement to existing treatments for MDD.
View details for DOI 10.1016/j.jad.2012.03.012
View details for Web of Science ID 000307434200013
View details for PubMedID 22464936
Some individuals have very specific and differentiated emotional experiences, such as anger, shame, excitement, and happiness, whereas others have more general affective experiences of pleasure or discomfort that are not as highly differentiated. Considering that individuals with major depressive disorder (MDD) have cognitive deficits for negative information, we predicted that people with MDD would have less differentiated negative emotional experiences than would healthy people. To test this hypothesis, we assessed participants' emotional experiences using a 7-day experience-sampling protocol. Depression was assessed using structured clinical interviews and the Beck Depression Inventory-II. As predicted, individuals with MDD had less differentiated emotional experiences than did healthy participants, but only for negative emotions. These differences were above and beyond the effects of emotional intensity and variability.
View details for DOI 10.1177/0956797612444903
View details for Web of Science ID 000314501400018
View details for PubMedID 23070307
A range of prefrontal and subcortical volumetric abnormalities have been found in adults and adolescents with bipolar disorder. It is unclear, however, if these deficits are present early in the onset of mania or are a consequence of multiple mood episodes or prolonged exposure to medication. The goal of this study was to examine whether youth with bipolar I disorder who recently experienced their first episode of mania are characterized by brain volumetric abnormalities.Anatomical images from magnetic resonance imaging of 26 13- to 18-year-old adolescents with bipolar I disorder and 24 age-comparable healthy controls with no personal or family history of psychopathology were analyzed using whole-brain voxel-based morphometry (VBM).Compared with healthy controls, adolescents with bipolar I disorder had significantly less gray matter volume in the left subgenual cingulate cortex [p<0.05, family-wise error (FWE)-corrected].Adolescents with a recent single episode of mania have smaller subgenual cingulate cortex volume than do their healthy counterparts, suggesting that this anomaly occurs early in the onset of, or may predate the disorder. Longitudinal studies are needed to examine the impact of this volumetric reduction on the course and outcome of this disorder.
View details for DOI 10.1111/j.1399-5618.2012.01043.x
View details for Web of Science ID 000308286800002
View details for PubMedID 22938166
Cognitive models of bipolar I disorder (BD) may aid in identification of children who are especially vulnerable to chronic mood dysregulation. Information-processing biases related to memory and attention likely play a role in the development and persistence of BD among adolescents; however, these biases have not been extensively studied in youth with BD.We administered the self-referent encoding task and the dot-probe task to adolescents with bipolar I disorder (BD, n = 35) and a demographically similar healthy comparison group (HC, n = 25) at baseline, and at a 1-year follow-up in a subset of this cohort (n = 22 per group).At both baseline and 1-year follow-up, there were significant interactions of group (BD, HC) and valence of stimulus (positive, negative adjective) on endorsement and recall of self-referent adjectives. HC adolescents endorsed and recalled more positive self-referent adjectives at baseline and follow-up while adolescents with BD endorsed and recalled more negative self-referent adjectives at baseline but not follow-up. Over time, depression symptomatology was associated with impaired memory for positive self-referent adjectives. There were no group differences in attentional bias at either time points.Adolescents with BD exhibit bias away from endorsement and recall of positive adjectives, which remained stable over time and independent of mood state.
View details for DOI 10.1111/j.1469-7610.2012.02543.x
View details for Web of Science ID 000307954500006
View details for PubMedID 22390273
Studies of puberty have focused primarily on changes in hormones and on observable physical bodily characteristics. Little is known, however, about the nature of the relation between pubertal status and brain physiology. This is particularly important given findings that have linked the onset of puberty with both changes in cognitive functioning and increases in the incidence of depression and anxiety. The present study examined relations between pubertal stage, as assessed by Tanner staging, and brain anatomy in a sample of 54 girls aged 9-15 years. Brain morphometric analysis was conducted using high-resolution magnetic resonance imaging (MRI). The hippocampus and amygdala were manually traced on MRI scans in all participants. Stepwise regression analyses were conducted with total intracranial volume (ICV), age, and pubertal status as the predictor variables and hippocampus and amygdala volumes as outcome variables. Pubertal status was significantly associated with left amygdala volume, after controlling for both age and ICV. In addition, puberty was related to right hippocampus and amygdala volumes, after controlling for ICV. In contrast, no significant associations were found between age and hippocampal and amygdala volumes after controlling for pubertal status and ICV. These findings highlight the importance of the relation between pubertal status and morphometry of the hippocampus and amygdala, and of limbic and subcortical structures that have been implicated in emotional and social behaviors.
View details for DOI 10.1016/j.neuroscience.2012.04.059
View details for Web of Science ID 000306156000011
View details for PubMedID 22569152
Previous studies have demonstrated that individuals with major depressive disorder have difficulties switching attention from one task set to another. In the current study we examined whether ruminative thinking drives the switching deficits of depressed individuals. A secondary, more exploratory, goal of this study was to examine whether state rumination would impair depressed individuals' ability to activate a new task set, to inhibit a no longer relevant task set, or both. Participants underwent either a rumination induction or a distraction induction and then completed a backward inhibition task that measures general switching abilities and the ability to inhibit previous task sets. Although depression was not related to switching ability as a main effect, depressed individuals who were induced to ruminate exhibited poorer switching ability than did both depressed and control individuals who were distracted from ruminating and control participants who were induced to ruminate. These findings suggest that depressed individuals are characterized by switching deficits only if they are ruminating. Moreover, the finding that state rumination did not affect participants' ability to inhibit previous task sets suggests that state rumination primarily impairs noninhibitory task-switching processes. It is interesting that the opposite pattern of results was obtained for trait rumination, which was related to inhibitory deficits during switching, but not to generally poorer switching. Thus, state and trait rumination may be associated with dissociable cognitive deficits.
View details for DOI 10.1037/a0027474
View details for Web of Science ID 000307482700003
View details for PubMedID 22468767
A growing body of evidence suggests that people with bipolar disorder are highly goal-oriented. Compared to other persons, they expend more effort to attain rewards and view goal pursuit as more important to their self-worth. Persons at risk for mania and those diagnosed with bipolar spectrum disorders have been shown to endorse highly ambitious life goals, such as becoming a multimillionaire or achieving fame. This study is the first examination of whether such elevated goals characterize persons diagnosed with bipolar I disorder. We also examined whether elevated ambitions predicted symptom change over time. Ninety-two persons with bipolar I disorder and 81 age- and sex-matched controls completed the Willingly Approached Set of Statistically Unlikely Pursuits, a measure of extremely high life ambitions. A subset of the bipolar participants completed a 3-month follow-up interview. Participants with bipolar disorder endorsed higher ambitions for popular fame than did controls; moreover, heightened ambitions for popular fame and financial success predicted increases in manic symptoms in those with bipolar disorder over the next three months. Discussion focuses on goal regulation in bipolar disorder.
View details for DOI 10.1037/a0026370
View details for Web of Science ID 000307482700006
View details for PubMedID 22103804
In this paper we examine the nature of automatic cognitive processing in anxiety disorders and Major Depressive Disorder (MDD). Rather than viewing automaticity as a unitary construct, we follow a social cognition perspective (Bargh, 1994) that argues for four theoretically independent features of automaticity: unconscious (processing of emotional stimuli occurs outside awareness), efficient (processing emotional meaning uses minimal attentional resources), unintentional (no goal is needed to engage in processing emotional meaning), and uncontrollable (limited ability to avoid, alter or terminate processing emotional stimuli). Our review of the literature suggests that most anxiety disorders are characterized by uncontrollable, and likely also unconscious and unintentional, biased processing of threat-relevant information. In contrast, MDD is most clearly typified by uncontrollable, but not unconscious or unintentional, processing of negative information. For the anxiety disorders and for MDD, there is no sufficient evidence to draw firm conclusions about efficiency of processing, though early indications are that neither anxiety disorders nor MDD are characterized by this feature. Clinical and theoretical implications of these findings are discussed and directions for future research are offered. In particular, it is clear that paradigms that more directly delineate the different features of automaticity are required to gain a more comprehensive and systematic understanding of the importance of automatic processing in emotion dysregulation.
View details for DOI 10.1016/j.cpr.2012.06.004
View details for Web of Science ID 000308049600013
View details for PubMedID 22858684
Functional neuroimaging investigations of major depressive disorder can advance both the neural theory and treatment of this debilitating illness. Inconsistency of neuroimaging findings and the use of region-of-interest approaches have hindered the development of a comprehensive, empirically informed neural model of major depression. In this context, the authors sought to identify reliable anomalies in baseline neural activity and neural response to affective stimuli in major depressive disorder.The authors applied voxel-wise, whole-brain meta-analysis to neuroimaging investigations comparing depressed to healthy comparison groups with respect to baseline neural activity or neural response to positively and/or negatively valenced stimuli.Relative to healthy subjects, those with major depression had reliably higher baseline activity, bilaterally, in the pulvinar nucleus. The analysis of neural response studies using negative stimuli showed greater response in the amygdala, insula, and dorsal anterior cingulate cortex and lower response in the dorsal striatum and dorsolateral prefrontal cortex in individuals with major depressive disorder than in healthy subjects.The meta-analytic results support an elegant and neuroanatomically viable model of the salience of negative information in major depressive disorder. In this proposed model, high baseline pulvinar activity in depression first potentiates responding of the brain's salience network to negative information; next, and owing potentially to low striatal dopamine levels in depression, this viscerally charged information fails to propagate up the cortical-striatal-pallidalthalamic circuit to the dorsolateral prefrontal cortex for contextual processing and reappraisal.
View details for DOI 10.1176/appi.ajp.2012.11071105
View details for Web of Science ID 000305853400007
View details for PubMedID 22535198
Depression is a prevalent and impairing psychiatric disorder that affects how we feel and how we think about ourselves and the world around us. Cognitive theories of depression have long posited that various thought processes are involved in the development, maintenance, and recurrence of depressive episodes. Contemporary research has utilized experimental procedures to examine cognitive processes in depressed individuals as well as the nature of the relation of these processes to the emotion dysregulation that is central to the disorder. For example, investigators have assessed the ways in which depression alters aspects of information processing, including attention and perception, interpretation, and memory processes; this research has generated relatively consistent findings. In addition, researchers have attempted to identify and elucidate the cognitive mechanisms that may link these biases in information processing to emotion dysregulation in depression. These mechanisms include inhibitory processes and deficits in working memory, ruminative responses to negative mood states, and the inability to use positive and rewarding stimuli to regulate negative mood. Results of these investigations converge on the formulation that depression is associated with increased elaboration of negative information, difficulties in cognitive control when processing this information, and difficulties disengaging from this information. Research examining cognitive aspects of depression not only enhances our understanding of this common and costly disorder, but also has implications for the treatment of depression and for future investigations of the biological foundations of this disorder.
View details for DOI 10.1002/wcs.1177
View details for Web of Science ID 000302867000003
View details for PubMedID 23240069
Although prescribed exercise has been found to improve affect and reduce levels of depression, we do not know how self-initiated everyday physical activity influences levels of positive affect (PA) and negative affect (NA) in depressed persons. Fifty-three individuals diagnosed with Major Depressive Disorder (MDD) and 53 never-depressed controls participated in a seven-day experience sampling study. Participants were prompted randomly eight times per day and answered questions about their physical activity and affective state. Over the week, the two groups of participants did not differ in average level of physical activity. As expected, participants with MDD reported lower average PA and higher average NA than did never-depressed controls. Both participants with MDD and controls reported higher levels of PA at prompts after physical activity than at prompts after inactive periods; moreover, for both groups of participants, PA increased from a prompt after an inactive period to a subsequent prompt at which activity was reported. Depressed participants in particular showed a dose-response effect of physical activity on affect: longer duration and/or higher intensity of physical activity increased their PA significantly more than did short duration and/or lower intensity physical activity. Physical activity did not influence NA in either group. In contrast to previous treatment studies that examined the effects of prescribed structured exercise, this investigation showed that self-initiated physical activity influences PA. These findings also underscore the importance of distinguishing between PA and NA to gain a more comprehensive understanding of the effects of physical activity on affect in MDD.
View details for DOI 10.1037/a0023533
View details for Web of Science ID 000304131400001
View details for PubMedID 21553939
Children of depressed parents are significantly more likely to develop depression and other mental health disorders than are children of never-depressed parents. Investigations of the physiological mechanisms underlying this elevated risk have generally focused on basal functioning. It is important to note, however, that physiological reactivity or responses to stress are also critical determinants of mental and physical health. In the current study, we examined whether children of depressed parents exhibit altered physiological responses to stress. In two studies, never-depressed adolescent daughters of either recurrently depressed mothers (RISK) or never-depressed mothers (CTL) underwent social stressors while their physiological responses were measured (cortisol in Study 1, heart rate in Study 2). In both studies, affective responses to the stressors predicted physiological responses in RISK girls, but not in never-depressed girls. For RISK girls, decreased positive affect in response to stress predicted increased cortisol reactivity; in addition, decreased positive affect and increased negative affect were associated with poorer heart rate recovery and habituation, respectively. Future research is needed to examine explicitly whether this coherence between affect and physiology is a mechanism underlying the increased risk for psychopathology in children of depressed parents.
View details for DOI 10.1017/S0954579412000235
View details for Web of Science ID 000302915900023
View details for PubMedID 22559138
View details for Web of Science ID 000302466000492
View details for Web of Science ID 000302466000250
View details for Web of Science ID 000302466000336
While major depressive disorder has been shown to be a significant mental health issue for school-age children, recent research indicates that depression can be observed in children as early as the preschool period. Yet, little work has been done to explore the neurobiological factors associated with this early form of depression. Given research suggesting a relation between adult depression and anomalies in emotion-related neural circuitry, the goal of the current study was to elucidate changes in functional activation during negative mood induction and emotion regulation in school-age children with a history of preschool-onset depression. The results suggest that a history of depression during the preschool period is associated with decreased activity in prefrontal cortex during mood induction and regulation. Moreover, the severity of current depressed mood was associated with increased activity in limbic regions, such as the amygdala, particularly in children with a history of depression. Similar to results observed in adult depression, the current findings indicate disruptions in emotion-related neural circuitry associated with preschool-onset depression.
View details for DOI 10.1016/j.dcn.2011.11.008
View details for Web of Science ID 000315317600006
View details for PubMedID 22483075
Daughters of depressed mothers are at significantly elevated risk for developing a depressive disorder themselves. We have little understanding, however, of the specific factors that contribute to this risk. The ability to regulate negative affect effectively is critical to emotional and physical health and may play an important role in influencing risk for depression. We examined whether never-disordered daughters whose mothers have experienced recurrent episodes of depression during their daughters' lifetime differ from never-disordered daughters of never-disordered mothers in their patterns of neural activation during a negative mood induction and during automatic mood regulation. Sad mood was induced in daughters through the use of film clips; daughters then recalled positive autobiographical memories, a procedure shown previously to repair negative affect. During the mood induction, high-risk girls exhibited greater activation than did low-risk daughters in brain areas that have frequently been implicated in the experience of negative affect, including the amygdala and ventrolateral prefrontal cortex. In contrast, during automatic mood regulation, low-risk daughters exhibited greater activation than did their high-risk counterparts in brain areas that have frequently been associated with top-down regulation of emotion, including the dorsolateral prefrontal cortex and dorsal anterior cingulate cortex. These findings indicate that girls at high and low risk for depression differ in their patterns of neural activation both while experiencing, and while repairing negative affect, and suggest that anomalies in neural functioning precede the onset of a depressive episode.
View details for DOI 10.1037/a0025294
View details for Web of Science ID 000300198500007
View details for PubMedID 21895344
Depression is characterized by sleep difficulties, but the extent to which subjective and objective sleep disturbances precede depression are unclear. This study was designed to examine perceptions of sleep quality in addition to actigraphy- and diary-measured sleep variables in healthy girls at low and high familial risk for major depressive disorder. Forty-four healthy daughters and their mothers completed a week of daily sleep diary and actigraphy; 24 girls had mothers with no history of psychopathology (low risk, mean age 14.92?years), and 20 girls had mothers with recurrent depression during the daughter's lifetime (high risk, mean age 14.12?years). All daughters had no current or past psychopathology. High-risk girls reported significantly poorer subjective sleep quality than did low-risk girls (P?=?0.001). The two groups of participants did not differ in actigraphy- or diary-measured sleep duration, onset latency or snooze duration. Healthy girls at high familial risk for depression report poorer sleep quality than do girls at low risk for depression, despite the absence of group differences in objective sleep disturbances as measured by actigraphy or daily diary. This pattern of findings may reflect a broader cognitive or physiological phenotype of risk for depression.
View details for DOI 10.1111/j.1365-2869.2011.00934.x
View details for Web of Science ID 000299332300009
View details for PubMedID 21702865
Anhedonia, the lack of interest or pleasure in response to hedonic stimuli or experiences, is a cardinal symptom of depression. This deficit in hedonic processing has been posited to influence depressed individuals' motivation to engage in potentially rewarding experiences. Accumulating evidence indicates that hedonic processing is not a unitary construct but rather consists of an anticipatory and a consummatory phase. We examined how these components of hedonic processing influence motivation to obtain reward in participants diagnosed with major depression and in never-disordered controls. Thirty-eight currently depressed and 30 never-disordered control participants rated their liking of humorous and nonhumorous cartoons and then made a series of choices between viewing a cartoon from either group. Each choice was associated with a specified amount of effort participants would have to exert before viewing the chosen cartoon. Although depressed and control participants did not differ in their consummatory liking of the rewards, levels of reward liking predicted motivation to expend effort for the rewards only in the control participants; in the depressed participants, liking and motivation were dissociated. In the depressed group, levels of anticipatory anhedonia predicted motivation to exert effort for the rewards. These findings support the formulation that anhedonia is not a unitary construct and suggest that, for depressed individuals, deficits in motivation for reward are driven primarily by low anticipatory pleasure and not by decreased consummatory liking.
View details for DOI 10.1037/a0024945
View details for Web of Science ID 000300198500006
View details for PubMedID 21842963
Researchers using experimental paradigms to examine cognitive processes have demonstrated that Major Depressive Disorder (MDD) is associated not with a general deficit in cognitive functioning, but instead with more specific anomalies in the processing of negatively valenced material. Indeed, cognitive theories of depression posit that negative biases in the processing of information play a critical role in influencing the onset, maintenance, and recurrence of depressive episodes. In this paper we review findings from behavioral studies documenting that MDD is associated with specific difficulties in attentional disengagement from negatively valenced material, with tendencies to interpret information in a negative manner, with deficits in cognitive control in the processing of negative material, and with enhanced memory for negative material. To gain a better understanding of the neurobiological basis of these abnormalities, we also examine findings from functional neuroimaging studies of depression and show that dysfunction in neural systems that subserve emotion processing, inhibition, and attention may underlie and contribute to the deficits in cognition that have been documented in depressed individuals. Finally, we briefly review evidence from studies of children who are at high familial risk for depression that indicates that abnormalities in cognition and neural function are observable before the onset of MDD and, consequently, may represent a risk factor for the development of this disorder. By integrating research from cognitive and neural investigations of depression, we can gain a more comprehensive understanding not only of how cognitive and biological factors interact to affect the onset, maintenance, and course of MDD, but also of how such research can aid in the development of targeted strategies for the prevention and treatment of this debilitating disorder.
View details for DOI 10.3389/fpsyg.2012.00489
View details for PubMedID 23162521
Despite advances in neurobiological research on Major Depressive Disorder and Social Anxiety Disorder, little is known about the neural functioning of individuals with comorbid depression/social anxiety. We examined the timing of neural responses to social stress in individuals with major depression and/or social anxiety. We hypothesized that having social anxiety would be associated with earlier responses to stress, having major depression would be associated with sustained responses to stress, and that comorbid participants would exhibit both of these response patterns.Participants were females diagnosed with pure depression (n?=?12), pure social anxiety (n?=?16), comorbid depression/social anxiety (n?=?17), or as never having had any Axis-I disorder (control; n?=?17). Blood oxygenation-level dependent activity (BOLD) was assessed with functional magnetic resonance imaging (fMRI). To induce social stress, participants prepared a speech that was ostensibly to be evaluated by a third party.Whereas being diagnosed with depression was associated with a resurgence of activation in the medial frontal cortex late in the stressor, having social anxiety was associated with a vigilance-avoidance activation pattern in the occipital cortex and insula. Comorbid participants exhibited activation patterns that generally overlapped with the non-comorbid groups, with the exception of an intermediate level of activation, between the level of activation of the pure depression and social anxiety groups, in the middle and posterior cingulate cortex.These findings advance our understanding of the neural underpinnings of major depression and social anxiety, and of their comorbidity. Future research should elucidate more precisely the behavioral correlates of these patterns of brain activation.
View details for DOI 10.1186/2045-5380-2-11
View details for PubMedID 22738335
In the present study we elucidate the emotional and executive control interactions that might underlie optimism and pessimism. Participants completed a self-report measure of optimism/pessimism and performed an emotion faces categorisation task and an emotion n-back task in which they indicated whether each of a series of faces had the same or a different emotional expression (happy, sad, neutral) as the face presented two trials before. Trials were structured to measure latency to update emotional content in working memory (WM). More pessimistic individuals formed connections among positive stimuli, and broke connections among positive and sad stimuli, in WM more slowly than did less pessimistic individuals; levels of optimism/pessimism did not affect the rate with which individuals formed and broke connections among neutral representations in WM. It appears, therefore, that levels of pessimism are related to specific affective cognitive mechanisms in WM that may be involved in emotion regulation.
View details for DOI 10.1080/02699931.2011.574110
View details for Web of Science ID 000301650700012
View details for PubMedID 22233460
In the current study, we examined the postulation that rumination makes it difficult for depressed individuals to learn the exact probability that different stimuli will be associated with punishment. To do so, we induced rumination or distraction in depressed and never-depressed participants and then measured punishment and reward sensitivity with a probabilistic selection task. In this task, participants first learn the probability that different stimuli will be associated with reward and punishment. During a subsequent test phase in which novel combinations of stimuli are presented, participants' sensitivity to reward is tested by measuring their tendency to select the stimuli that were most highly rewarded during training, and their sensitivity to punishment is tested by measuring their tendency to not select the stimuli that were most highly punished during training. Compared with distraction, rumination led depressed participants to be less sensitive to the probability that stimuli will be associated with punishment and relatively less sensitive to punishment than reward. Never-depressed participants and depressed participants who were distracted from rumination were as sensitive to reward as they were to punishment. The effects of rumination on sensitivity to punishment may be a mechanism by which rumination can lead to maladaptive consequences.
View details for DOI 10.1080/02699931.2012.682973
View details for Web of Science ID 000310736900009
View details for PubMedID 22716241
Theorists contend that emotional awareness is vital to being able to use emotional information adaptively. The extent to which individuals attend to and value their feelings, or attention to emotion, is a facet of emotional awareness. Little research, however, has examined whether attention to emotion affects the magnitude or intensity of emotional experiences. In the present study we examined the relations between attention to emotion and levels of affect in 53 healthy adults. Participants carried hand-held electronic devices for approximately 7 days and were randomly prompted eight times per day to answer a series of questions. At each prompt, participants reported attention to emotion, current negative affect (NA), and positive affect (PA). All findings presented were computed using multilevel modeling. Replicating findings obtained using trait-level measures, we found that attention to emotion was associated concurrently with higher levels of both NA and PA. We also found prospectively that attention to emotion at one prompt predicted a decrease in levels of NA, but no change in levels of PA, at the subsequent prompt. These findings suggest that emotional processes serve different functions over time and highlight the role of attention to emotion in affect regulation. (PsycINFO Database Record (c) 2011 APA, all rights reserved).
View details for DOI 10.1037/a0022822
View details for Web of Science ID 000297921200028
View details for PubMedID 21534663
Vector autoregression (VAR) and structural equation modeling (SEM) are two popular brain-network modeling tools. VAR, which is a data-driven approach, assumes that connected regions exert time-lagged influences on one another. In contrast, the hypothesis-driven SEM is used to validate an existing connectivity model where connected regions have contemporaneous interactions among them. We present the two models in detail and discuss their applicability to FMRI data, and their interpretational limits. We also propose a unified approach that models both lagged and contemporaneous effects. The unifying model, structural vector autoregression (SVAR), may improve statistical and explanatory power, and avoid some prevalent pitfalls that can occur when VAR and SEM are utilized separately.
View details for DOI 10.1016/j.compbiomed.2011.09.004
View details for Web of Science ID 000298200700011
View details for PubMedID 21975109
Sleep disturbance is an early marker for bipolar disorder (BD) onset in youth. We characterized sleep quality in adolescents experiencing mania within the last 6-12 months. We examined the association between mood and sleep in 27 adolescents with BD and 24 matched healthy controls (HC). Subjects were assessed by parent and teen report of sleep, a semi-structured clinical interview, the Young Mania Rating Scale (YMRS), and the Childhood Depression Rating Scale (CDRS-R). Average BD youth YMRS (mean 20.3 ± 7.3) and CDRS-R (mean 42.4 ± 14.1) scores indicated they were still ill at time of assessment. Compared to HCs, adolescents with BD have distinct patterns of prolonged sleep onset latency, frequent nighttime awakenings, and increased total time awake. Mood symptoms, specifically excessive guilt, self-injurious behavior, and worsening evening mood, interfered with sleep. Further studies are needed to determine whether early regulation of sleep would improve long-term outcome in BD youth.
View details for DOI 10.1007/s10578-011-0239-0
View details for Web of Science ID 000296879200008
View details for PubMedID 21701911
Responses to stress vary greatly in young adolescents, and little is known about neural correlates of the stress response in youth. The purpose of this study was to examine whether variability in cortisol responsivity following a social stress test in young adolescents is associated with altered neural functional connectivity (FC) of the salience network (SN) measured during resting-state functional magnetic resonance imaging (rs-fMRI).Forty-nine typically developing young adolescents participated in a social stress test during which they contributed salivary cortisol samples. Following this, they underwent rs-fMRI scanning. We examined the association of FC of the SN [composed of anterior cingulate cortex and bilateral anterior insula regions] with cortisol responsivity.Greater cortisol responsivity was significantly positively correlated with higher FC between subgenual anterior cingulate cortex (Cg25) and the SN, controlling for participant age. There were no regions of the brain that showed an inverse relation.Brain systems that have been implicated in autonomic arousal and that influence subjective feeling states show altered FC associated with stress responsivity in early life.
View details for DOI 10.1111/j.1469-7610.2011.02422.x
View details for Web of Science ID 000295119700003
View details for PubMedID 21644985
Field studies and laboratory experiments have documented that a key component of resilience is emotional flexibility--the ability to respond flexibly to changing emotional circumstances. In the present study we tested the hypotheses that resilient people exhibit emotional flexibility: (a) in response to frequently changing emotional stimuli and (b) across multiple modalities of emotional responding. As participants viewed a series of emotional pictures, we assessed their self-reported affect, facial muscle activity, and startle reflexes. Higher trait resilience predicted more divergent affective and facial responses (corrugator and zygomatic) to positive versus negative pictures. Thus, compared with their low-resilient counterparts, resilient people appear to be able to more flexibly match their emotional responses to the frequently changing emotional stimuli. Moreover, whereas high-trait-resilient participants exhibited divergent startle responses to positive versus negative pictures regardless of the valence of the preceding trial, low-trait-resilient participants did not exhibit divergent startle responses when the preceding picture was negative. High-trait-resilient individuals, therefore, appear to be better able than are their low-resilient counterparts to either switch or maintain their emotional responses depending on whether the emotional context changes. The present findings broaden our understanding of the mechanisms underlying resilience by demonstrating that resilient people are able to flexibly change their affective and physiological responses to match the demands of frequently changing environmental circumstances.
View details for DOI 10.1037/a0021786
View details for Web of Science ID 000295372600006
View details for PubMedID 21707168
We examined the neural basis of self-regulation in individuals from a cohort of preschoolers who performed the delay-of-gratification task 4 decades ago. Nearly 60 individuals, now in their mid-forties, were tested on "hot" and "cool" versions of a go/nogo task to assess whether delay of gratification in childhood predicts impulse control abilities and sensitivity to alluring cues (happy faces). Individuals who were less able to delay gratification in preschool and consistently showed low self-control abilities in their twenties and thirties performed more poorly than did high delayers when having to suppress a response to a happy face but not to a neutral or fearful face. This finding suggests that sensitivity to environmental hot cues plays a significant role in individuals' ability to suppress actions toward such stimuli. A subset of these participants (n = 26) underwent functional imaging for the first time to test for biased recruitment of frontostriatal circuitry when required to suppress responses to alluring cues. Whereas the prefrontal cortex differentiated between nogo and go trials to a greater extent in high delayers, the ventral striatum showed exaggerated recruitment in low delayers. Thus, resistance to temptation as measured originally by the delay-of-gratification task is a relatively stable individual difference that predicts reliable biases in frontostriatal circuitries that integrate motivational and control processes.
View details for DOI 10.1073/pnas.1108561108
View details for Web of Science ID 000294543400057
View details for PubMedID 21876169
Although exposure to early adversity and prior experiences with depression have both been associated with lower levels of precipitating life stress in depression, it is unclear whether these stress sensitization effects are similar for all types of stress or whether they are specific to stressors that may be particularly depressogenic, such as those involving interpersonal loss. To investigate this issue, we administered structured, interview-based measures of early adversity, depression history, and recent life stress to one hundred adults who were diagnosed with major depressive disorder. As predicted, individuals who experienced early parental loss or prolonged separation (i.e., lasting one year or longer) and persons with more lifetime episodes of depression became depressed following lower levels of life stress occurring in the etiologically-central time period of three months prior to onset of depression. Importantly, however, additional analyses revealed that these effects were unique to stressors involving interpersonal loss. These data highlight potential stressor-specific effects in stress sensitization and demonstrate for the first time that individuals exposed to early parental loss or separation, and persons with greater histories of MDD, may be selectively sensitized to stressors involving interpersonal loss.
View details for DOI 10.1016/j.jpsychires.2011.03.004
View details for Web of Science ID 000294885400003
View details for PubMedID 21470621
Postnatally depressed mothers have difficulties responding appropriately to their infants. The quality of the mother-child relationship depends on a mother's ability to respond to her infant's cues, which are largely non-verbal. Therefore, it is likely that difficulties in a mother's appraisal of her infants' facial expressions will affect the quality of mother-infant interaction. This study aimed to investigate the effects of postnatal depression and anxiety on the processing of infants' facial expressions.A total of 89 mothers, 34 with Generalised Anxiety Disorder, 21 with Major Depressive Disorder, and 34 controls, completed a 'morphed infants' faces task when their children were between 10 and 18 months.Overall, mothers were more likely to identify happy faces accurately and at lower intensity than sad faces. Depressed compared to control participants, however, were less likely to accurately identify happy infant faces. Interestingly, mothers with GAD tended to identify happy faces at a lower intensity than controls. There were no differences between the groups in relation to sad faces.Our sample was relatively small and further research is needed to investigate the links between mothers' perceptions of infant expressions and both maternal responsiveness and later measures of child development.Our findings have potential clinical implications as the difficulties in the processing of positive facial expressions in depression may lead to less maternal responsiveness to positive affect in the offspring and may diminish the quality of the mother-child interactions. Results for participants with GAD are consistent with the literature demonstrating that persons with GAD are intolerant of uncertainty and seek reassurance due to their worries.
View details for DOI 10.1016/j.jad.2011.04.015
View details for Web of Science ID 000294934700024
View details for PubMedID 21641652
Major depressive disorder (MDD) has been associated reliably with ruminative responding; this kind of responding is composed of both maladaptive and adaptive components. Levels of activity in the default-mode network (DMN) relative to the task-positive network (TPN), as well as activity in structures that influence DMN and TPN functioning, may represent important neural substrates of maladaptive and adaptive rumination in MDD.We used a unique metric to estimate DMN dominance over TPN from blood oxygenation level-dependent data collected during eyes-closed rest in 17 currently depressed and 17 never-disordered adults. We calculated correlations between this metric of DMN dominance over TPN and the depressive, brooding, and reflective subscales of the Ruminative Responses Scale, correcting for associations between these measures both with one another and with severity of depression. Finally, we estimated and compared across groups right fronto-insular cortex (RFIC) response during initiations of ascent in DMN and in TPN activity.In the MDD participants, increasing levels of DMN dominance were associated with higher levels of maladaptive, depressive rumination and lower levels of adaptive, reflective rumination. Moreover, our RFIC state-change analysis showed increased RFIC activation in the MDD participants at the onset of increases in TPN activity; conversely, healthy control participants exhibited increased RFIC response at the onset of increases in DMN activity.These findings support a formulation in which the DMN undergirds representation of negative, self-referential information in depression, and the RFIC, when prompted by increased levels of DMN activity, initiates an adaptive engagement of the TPN.
View details for DOI 10.1016/j.biopsych.2011.02.003
View details for Web of Science ID 000293080400011
View details for PubMedID 21459364
Cognitive inflexibility may play an important role in rumination, a risk factor for the onset and maintenance of depressive episodes. In the study reported here, we assessed participants' ability to either reverse or maintain in working memory the order of three emotion or three neutral words. Differences (or sorting costs) between response latencies in backward trials, on which participants were asked to reverse the order of the words, and forward trials, on which participants were asked to remember the words in the order in which they were presented, were calculated. Compared with control participants, depressed participants had higher sorting costs, particularly when presented with negative words. It is important to note that rumination predicted sorting costs for negative words but not for positive or neutral words in the depressed group. These findings indicate that depression and rumination are associated with deficits in cognitive control.
View details for DOI 10.1177/0956797611415539
View details for Web of Science ID 000294709400001
View details for PubMedID 21742932
Depression and bulimia both are associated with low serotonin levels. We examined whether the serotonin transporter gene (5-HTTLPR) moderates the relation between depressive and bulimic symptoms over time.Fifty adolescent girls with no current or past Axis I disorder were genotyped for the 5-HTTLPR gene. Twice, 6 months apart, participants completed self-report measures of depressive symptoms and bulimic symptoms.The association between change in depressive symptoms and change in bulimic symptoms over time was significantly stronger in girls who are homozygous for the short 5-HTTLPR allele than for girls with at least one long allele.This finding is consistent with previous studies documenting a relation between depressive and bulimic symptoms in adolescents. Few studies, however, considered the possible role of serotonin linking both disorders. Gaining a better understanding of developmental effects of low serotonin could help to identify high-risk individuals and provide effective prevention and intervention.
View details for DOI 10.1002/eat.20850
View details for Web of Science ID 000291614200001
View details for PubMedID 21661000
Major Depressive Disorder (MDD) has been conceptualized as a neural network-level disease. Few studies of the neural bases of depression, however, have used analytical techniques that are capable of testing network-level hypotheses of neural dysfunction in this disorder. Moreover, of those that have, fewer still have attempted to determine the directionality of influence within functionally abnormal networks of structures. We used multivariate GC analysis, a technique that estimates the extent to which preceding neural activity in one or more seed regions predicts subsequent activity in target brain regions, to analyze blood-oxygen-level-dependent (BOLD) data collected during eyes-closed rest from depressed and never-depressed persons. We found that activation in the hippocampus predicted subsequent increases in ventral anterior cingulate cortex (vACC) activity in depression, and that activity in the medial prefrontal cortex and vACC were mutually reinforcing in MDD. Hippocampal and vACC activation in depressed participants predicted subsequent decreases in dorsal cortical activity. This study shows that, on a moment-by-moment basis, there is increased excitatory activity among limbic and paralimbic structures, as well as increased inhibition in the activity of dorsal cortical structures, by limbic structures in depression; these aberrant patterns of effective connectivity implicate disturbances in the mesostriatal dopamine system in depression. These findings advance the neural theory of depression by detailing specific patterns of limbic excitation in MDD, by making explicit the primary role of limbic inhibition of dorsal cortex in the cortico-limbic relation posited to underlie depression, and by presenting an integrated neurofunctional account of altered dopamine function in this disorder.
View details for DOI 10.1038/mp.2010.46
View details for Web of Science ID 000291973300011
View details for PubMedID 20479758
The oxytocin system plays a significant role in modulating stress responses in animals and humans; perturbations in this system may contribute to the pathogenesis of psychiatric disorder. Attempts to identify clinically relevant genetic variants in the oxytocin system have yielded associations between polymorphisms of the oxytocin receptor (OXTR) gene and both autism and major depression. To date, however, little is known about how such variants affect brain structures implicated in these disorders. Applying a manual tracing procedure to high-resolution structural magnetic resonance images, amygdala volumes were measured in 51 girls genotyped on OXTR rs2254298(G>A), a single nucleotide polymorphism associated with psychopathology. Results of this study indicate that despite having greater gray matter volume, participants homozygous for the G allele were characterized by smaller volumes of both left and right amygdala than were carriers of the A allele. A subsequent whole-brain voxel-based morphometry analysis revealed additional genotype-mediated volumetric group differences in the posterior brain stem and dorsomedial anterior cingulate cortex. These findings highlight one neurobiological pathway by which oxytocin gene variants may increase risk for psychopathology. Further research is needed to characterize the mechanism by which this polymorphism contributes to anatomical variability and to identify functional correlates of these alterations in regional brain volume.
View details for DOI 10.1016/j.psyneuen.2010.12.004
View details for Web of Science ID 000292237500014
View details for PubMedID 21208749
This study used a comprehensive, interview-based measure of life stress to assess the role of different types of stress in predicting first onset of psychiatric disorders among daughters of depressed (n = 22) mothers and healthy (n = 22) mothers. Several types of stress were assessed: Chronic interpersonal stress, chronic non-interpersonal stress, episodic dependent (i.e., self-generated) interpersonal stress, episodic dependent non-interpersonal stress, episodic independent interpersonal stress, and episodic independent non-interpersonal stress. Daughters (ages 9-14) were recruited to have no clinically significant symptoms upon entry (T1). By a 30-month follow-up assessment (T2), 45% of the daughters of depressed mothers, but none of the daughters of healthy mothers, had developed a psychiatric disorder. Overall, daughters of depressed mothers were exposed to more severe chronic interpersonal and non-interpersonal stress than were daughters of healthy mothers. Further, daughters of depressed mothers who developed a psychiatric disorder by T2 were exposed to more severe chronic non-interpersonal stress and episodic dependent stress than were daughters of depressed mothers who remained healthy. We discuss the implications of these findings in the context of a stress-generation model for the intergenerational transmission of psychiatric risk among children of depressed mothers.
View details for DOI 10.1016/j.jpsychires.2011.03.016
View details for Web of Science ID 000292667900001
View details for PubMedID 21524424
A functional variant of the serotonin transporter gene (5-HTTLPR) has been associated with increased risk for major depression in the context of stress. In attempting to understand the mechanisms underlying this relation, we tested the hypothesis that 5-HTTLPR genotype affects the speed with which amygdala is recruited during emotional processing in young girls with no history of psychiatric disorder. We used functional magnetic resonance imaging to compare the rise time to peak amygdala activation in 5-HTTLPR short-allele carriers and long-allele homozygotes during enhancement of sad mood. Relative to long-allele homozygotes, participants with at least one copy of the 5-HTTLPR short allele showed both stronger and earlier activation in left amygdala as they increased a sad mood state. Individuals carrying the short allele appear to exhibit a neural 'readiness' to engage and enhance negative affect. Future research should examine how exposure to negative life events and more chronic sadness modify the time course of amygdala activity during the experience of negative emotion.
View details for DOI 10.1093/scan/nsq029
View details for Web of Science ID 000291543600003
View details for PubMedID 20360351
Bipolar disorder (BD) is a chronic psychiatric illness that impairs quality of life (QoL) in numerous life domains even when mood symptoms are not present and is characterized by elevated impulsivity. Many of the comorbid conditions that are associated with diminished QoL in BD also involve impulsivity. The objective of this project was to investigate whether impulsivity might mediate the effects of these comorbid conditions on poor QoL.A total of 76 participants diagnosed with bipolar I disorder by the Structured Clinical Interview for DSM-IV Axis I disorders completed the Quality of Life in Bipolar Disorder (QoL-BD) scale, the Barratt Impulsivity Scale (BIS-11), and the Positive Urgency Measure (PUM). Participants were also assessed for comorbid DSM-IV diagnoses of anxiety, substance use, and impulse control disorders.Several subscales of the BIS-11 as well as the PUM total score were significantly negatively correlated with overall QoL. PUM total score remained a significant predictor of QoL after controlling for comorbid anxiety, substance use, and impulse control disorders. After controlling for impulsivity, comorbid disorders were no longer significantly related to overall QoL.The data support the hypothesis that impulsivity, specifically positive urgency, is highly correlated with QoL in BD. Impulsivity was found to mediate the relation between QoL and several comorbidities in BD. Interventions targeting impulsivity might help to improve QoL in BD.
View details for DOI 10.1111/j.1399-5618.2011.00919.x
View details for Web of Science ID 000292666000009
View details for PubMedID 21676133
In the 1960s, Mischel and colleagues developed a simple 'marshmallow test' to measure preschoolers' ability to delay gratification. In numerous follow-up studies over 40?years, this 'test' proved to have surprisingly significant predictive validity for consequential social, cognitive and mental health outcomes over the life course. In this article, we review key findings from the longitudinal work and from earlier delay-of-gratification experiments examining the cognitive appraisal and attention control strategies that underlie this ability. Further, we outline a set of hypotheses that emerge from the intersection of these findings with research on 'cognitive control' mechanisms and their neural bases. We discuss implications of these hypotheses for decomposing the phenomena of 'willpower' and the lifelong individual differences in self-regulatory ability that were identified in the earlier research and that are currently being pursued.
View details for DOI 10.1093/scan/nsq081
View details for Web of Science ID 000291543100011
View details for PubMedID 20855294
Individuals diagnosed with major depressive disorder (MDD) often ruminate about their depression and their life situations, impairing their concentration and performance on daily tasks. We examined whether rumination might be due to a deficit in the ability to expel negative information from short-term memory (STM), and fMRI was used to examine the neural structures involved in this ability. MDD and healthy control (HC) participants were tested using a directed-forgetting procedure in a short-term item recognition task. As predicted, MDD participants had more difficulty than did HCs in expelling negative, but not positive, words from STM. Overall, the neural networks involved in directed forgetting were similar for both groups, but the MDDs exhibited more spatial variability in activation in the left inferior frontal gyrus (a region critical for inhibiting irrelevant information), which may contribute to their relative inability to inhibit negative information.
View details for DOI 10.3758/s13415-010-0014-x
View details for Web of Science ID 000290029000008
View details for PubMedID 21264648
Resting-state MRI (rs-fMRI) is a powerful procedure for studying whole-brain neural connectivity. In this study we provide the first empirical evidence of the longitudinal reliability of rs-fMRI in children. We compared rest-retest measurements across spatial, temporal and frequency domains for each of six cognitive and sensorimotor intrinsic connectivity networks (ICNs) both within and between scan sessions. Using Kendall'sW, concordance of spatial maps ranged from .60 to .86 across networks, for various derived measures. The Pearson correlation coefficient for temporal coherence between networks across all Time 1-Time 2 (T1/T2) z-converted measures was .66 (p<.001). There were no differences between T1/T2 measurements in low-frequency power of the ICNs. For the visual network, within-session T1 correlated with the T2 low-frequency power, across participants. These measures from resting-state data in children were consistent across multiple domains (spatial, temporal, and frequency). Resting-state connectivity is therefore a reliable method for assessing large-scale brain networks in children.
View details for DOI 10.1016/j.neuroimage.2010.11.080
View details for Web of Science ID 000287008900014
View details for PubMedID 21134471
The nonapeptide oxytocin and its receptor have been implicated in the regulation of mammalian social behavior and stress physiology. Evidence is accumulating that the quality of the parental environment is associated with oxytocin biology in children. The present study was designed to examine the interaction of the single nucleotide polymorphism (SNP) rs2254298 within the oxytocin receptor (OXTR) gene and quality of parental environment in predicting children's psychosocial functioning. More specifically, in a sample of 92 Caucasian adolescent girls (9-14 years old), we examined whether adverse parental environment, operationalized as mothers' history of recurrent major depressive disorder, interacts with the rs2254298 SNP on the OXTR gene to predict daughters' symptoms of depression and anxiety. Caucasian girls who both were heterozygous for the OXTR rs2254298 polymorphism and had high early adversity reported the highest levels of symptoms of depression, physical anxiety, and social anxiety. These findings highlight the potential importance of this OXTR gene polymorphism in the etiology of depression and anxiety disorders.
View details for DOI 10.1016/j.psyneuen.2010.07.003
View details for Web of Science ID 000286299100016
View details for PubMedID 20708845
The advent of real-time neurofeedback techniques has allowed us to begin to map the controllability of sensory and cognitive and, more recently, affective centers in the brain. The subgenual anterior cingulate cortex (sACC) is thought to be involved in generation of affective states and has been implicated in psychopathology. In this study, we examined whether individuals could use real-time fMRI neurofeedback to modulate sACC activity. Following a localizer task used to identify an sACC region of interest, an experimental group of eight women participated in four scans: (1) a pretraining scan in which they were asked to decrease activity in the sACC without neurofeedback; (2) two training scans in which sACC neurofeedback was presented along with instructions to decrease sACC activity; and (3) a neurofeedback-free post-training scan. An additional nine women in a yoked feedback control group saw sACC activity from the participants in the experimental group. Activity in the sACC was significantly reduced during neurofeedback training in the experimental group, but not in the control group. This training effect in the experimental group, however, did not generalize to the neurofeedback-free post-training scan. A psychophysiological interaction analysis showed decreased correlation in the experimental group relative to the sham control group between activity in the sACC and the posterior cingulate cortex during neurofeedback training relative to neurofeedback-free scans. The finding that individuals can down-modulate the sACC shows that a primary emotion center in which functional abnormality has been strongly implicated in affective disorders can be controlled with the aid of neurofeedback.
View details for DOI 10.1002/hbm.20997
View details for Web of Science ID 000285398000003
View details for PubMedID 21157877
Research on resting-state functional connectivity reveals intrinsically connected networks in the brain that are largely consistent across the general population. However, there are individual differences in these networks that have not been elucidated. Here, we measured the influence of naturally occurring mood on functional connectivity. In particular, we examined the association between self-reported levels of anxiety and connectivity in the default mode network (DMN). Healthy youth (n=43; ages 10-18) and adult participants (n=24, ages 19-59) completed a 6-min resting-state functional magnetic resonance imaging scan, then immediately completed questionnaires assessing their mood and thoughts during the scan. Regression analyses conducted separately for the youth and adult samples revealed brain regions in which increases in connectivity differentially corresponded to higher anxiety in each group. In one area, the left insular cortex, both groups showed similar increased connectivity to the DMN (youth: -30, 26, 14; adults: -33, 12, 14) with increased anxiety. State anxiety assessed during scanning was not correlated with trait anxiety, so our results likely reflect state levels of anxiety. To our knowledge, this is the first study to relate naturally occurring mood to resting state connectivity.
View details for DOI 10.1089/brain.2011.0030
View details for PubMedID 22433052
Ordinary variations in human infants' attachment behaviors - their proclivity to seek and accept comfort from caregivers - are associated with a wide range of individual differences in psychological functioning in adults. The current investigation examined variation in the oxytocin receptor (OXTR) gene as one possible source of these variations in infant attachment. One hundred seventy-six infants (77 Caucasian, 99 non-Caucasian) were classified as securely or insecurely attached based on their behavior in the Strange Situation (Ainsworth et al., 1978). The A allele of OXTR rs2254298 was associated with attachment security in the non-Caucasian infants (p?0.005). These findings underscore the importance of oxytocin in the development of human social behavior and support its role in social stress-regulation and the development of trust.
View details for DOI 10.3389/fpsyg.2011.00200
View details for PubMedID 21904531
Attentional biases for negative stimuli have been observed in school-age and adolescent children of depressed mothers and may reflect a vulnerability to depression. The direction of these biases and whether they can be identified in early childhood remains unclear. The current study examined attentional biases in 5-7-year-old children of depressed and non-depressed mothers. Following a mood induction, children participated in a dot-probe task assessing biases for sad and happy faces. There was a significant interaction of group and sex: daughters of depressed mothers attended selectively to sad faces, while children of controls and sons of depressed mothers did not exhibit biases. No effects were found for happy stimuli. These findings suggest that attentional biases are discernible in early childhood and may be vulnerability markers for depression. The results also raise the possibility that sex differences in cognitive biases are evident before the emergence of sex differences in the prevalence of depression.
View details for DOI 10.1007/s10802-010-9438-6
View details for Web of Science ID 000287149500011
View details for PubMedID 20644991
Abnormalities of the striatum and frontal cortex have been reported consistently in studies of neural structure and function in major depressive disorder (MDD). Despite speculation that compromised connectivity between these regions may underlie symptoms of MDD, little work has investigated the integrity of frontostriatal circuits in this disorder.Functional magnetic resonance images were acquired from 21 currently depressed and 19 never-disordered women during wakeful rest. Using four predefined striatal regions-of-interest, seed-to-whole brain correlations were computed and compared between groups.Compared to controls, depressed participants exhibited attenuated functional connectivity between the ventral striatum and both ventromedial prefrontal cortex and subgenual anterior cingulate cortex. Depressed participants also exhibited stronger connectivity between the dorsal caudate and dorsal prefrontal cortex, which was positively correlated with severity of the disorder.Depressed individuals are characterized by aberrant connectivity in frontostriatal circuits that are posited to support affective and cognitive processing. Further research is required to examine more explicitly the link between patterns of disrupted connectivity and specific symptoms of depression, and the extent to which these patterns precede the onset of depression and normalize with recovery from depressive illness.
View details for DOI 10.1186/2045-5380-1-11
View details for PubMedID 22737995
Depressed persons have better memory for affectively negative than positive stimuli, a pattern generally not exhibited by non-depressed individuals. The mechanisms underlying this differential memory are not clear. In this study we examined memory for valenced and neutral stimuli in depressed and non-depressed individuals under conditions of relatively unconstrained encoding. We developed a novel task based on the game, Concentration, in which participants tried to match pairs of positive and negative words, and pairs of neutral words, hidden under squares in as few turns as possible. Whereas non-depressed participants selected and turned over positive squares more frequently than they did negative squares, depressed participants selected and turned over positive and negative squares equally often. Depressed participants also matched fewer positive word pairs within the first five minutes of the task than did non-depressed participants, and they exhibited poorer learning of positive words. Depressed and non-depressed participants did not differ in their matching of neutral words. These findings add to a growing literature indicating that depression is characterised by difficulties in the processing of positive stimuli.
View details for DOI 10.1080/02699931.2010.538374
View details for Web of Science ID 000299564700010
View details for PubMedID 21432643
Rumination, or recursive self-focused thinking, has important implications for understanding the development and maintenance of depressive episodes. Rumination is associated with the worsening of negative mood states, greater affective responding to negative material, and increased access to negative memories. The present study was designed to use fMRI to examine neural aspects of rumination in depressed and healthy control individuals. We used a rumination induction task to assess differences in patterns of neural activation during ruminative self-focus as compared with a concrete distraction condition and with a novel abstract distraction condition in 14 participants who were diagnosed with major depressive disorder and 14 healthy control participants. Depressed participants exhibited increased activation in the orbitofrontal cortex, subgenual anterior cingulate, and dorsolateral prefrontal cortex as compared with healthy controls during rumination versus concrete distraction. Neural activity during rumination versus abstract distraction was greater for depressed than for control participants in the amygdala, rostral anterior cingulate/medial prefrontal cortex, dorsolateral prefrontal cortex, posterior cingulate, and parahippocampus. These findings indicate that ruminative self-focus is associated with enhanced recruitment of limbic and medial and dorsolateral prefrontal regions in depression. Supplemental materials for this article may be downloaded from http://cabn.psychonomic-journals.org/content/supplemental.
View details for DOI 10.3758/CABN.10.4.470
View details for Web of Science ID 000285439000005
View details for PubMedID 21098808
Diffusion tensor imaging is widely used to evaluate the development of white matter. Information about how alterations in major neurotransmitter systems, such as the dopamine (DA) system, influence this development in healthy children, however, is lacking. Catechol-O-metyltransferase (COMT) is the major enzyme responsible for DA degradation in prefrontal brain structures, for which there is a corresponding genetic polymorphism (val158met) that confers either a more or less efficient version of this enzyme. The result of this common genetic variation is that children may have more or less available synaptic DA in prefrontal brain regions. In the present study we examined the relation between diffusion properties of frontal white matter structures and the COMT val158met polymorphism in 40 children ages 9-15. We found that the val allele was associated with significantly elevated fractional anisotropy values and reduced axial and radial diffusivities. These results indicate that the development of white matter in healthy children is related to COMT genotype and that alterations in white matter may be related to the differential availability of prefrontal DA. This investigation paves the way for further studies of how common functional variants in the genome might influence the development of brain white matter.
View details for DOI 10.1016/j.neuroimage.2010.01.033
View details for Web of Science ID 000282039300015
View details for PubMedID 20083203
Difficulties in the ability to update stimuli in working memory (WM) may underlie the problems with regulating emotions that lead to the development and perpetuation of mood disorders such as depression. To examine the ability to update affective material in WM, the authors had diagnosed depressed and never-disordered control participants perform an emotion 2-back task in which participants were presented with a series of happy, sad, and neutral faces and were asked to indicate whether the current face had the same (match-set) or different (break-set or no-set) emotional expression as that presented 2 faces earlier. Participants also performed a 0-back task with the same emotional stimuli to serve as a control for perceptual processing. After transforming reaction times to control for baseline group differences, depressed and nondepressed participants exhibited biases in updating emotional content that reflects the tendency to keep negative information and positive information, respectively, active in WM. Compared with controls, depressed participants were both slower to disengage from sad stimuli and faster to disengage from happy facial expressions. In contrast, nondepressed controls took longer to disengage from happy stimuli than from neutral or sad stimuli. These group differences in reaction times may reflect both protective and maladaptive biases in WM that underlie the ability to effectively regulate negative affect.
View details for DOI 10.1037/a0020283
View details for Web of Science ID 000284442500006
View details for PubMedID 21038984
Theoretical models attempting to explain why approximately twice as many women as men suffer from depression often involve the role of stressful life events. However, detailed empirical evidence regarding gender differences in rates of life events that precede onset of depression is lacking, due in part to the common use of checklist assessments of stress that have been shown to possess poor validity. The present study reports on a combined sample of 375 individuals drawn from 4 studies in which all participants were diagnosed with major depressive disorder and assessed with the Life Events and Difficulties Schedule (Bifulco et al., 1989), a state-of-the-art contextual interview and life stress rating system. Women reported significantly more severe and nonsevere, independent and dependent, and other-focused and subject-focused life events prior to onset of depression than did men. Further, these relations were significantly moderated by age, such that gender differences in rates of most types of events were found primarily in young adulthood. These results are discussed in term of their implications for understanding the etiological role of stressful life events in depression.
View details for DOI 10.1037/a0020629
View details for Web of Science ID 000284247200015
View details for PubMedID 20853920
Recent evidence suggests that a genetic polymorphism in the promoter region (5-HTTLPR) of the serotonin transporter gene (SLC6A4) mediates stress reactivity in adults. Little is known, however, about this gene-brain association in childhood and adolescence, generally conceptualized as a time of heightened stress reactivity. The present study examines the association between 5-HTTLPR allelic variation and responses to fearful and angry faces presented both sub- and supraliminally in participants, ages 9-17. Behaviorally, carriers of the 5-HTTLPR short (s) allele exhibited significantly greater attentional bias to subliminally presented fear faces than did their long (l)-allele homozygous counterparts. Moreover, s-allele carriers showed greater neural activations to fearful and angry faces than did l-allele homozygotes in various regions of association cortex previously linked to attention control in adults. These results indicate that in children and adolescents, s-allele carriers can be distinguished from l-allele homozygotes on the basis of hypervigilant behavioral and neural processing of negative material.
View details for DOI 10.1016/j.biopsycho.2010.04.009
View details for Web of Science ID 000281182600005
View details for PubMedID 20493234
Rumination has consistently been found to be associated with the onset and duration of major depressive episodes. Little research, however, has examined factors that may weaken the association between maladaptive coping, such as rumination, and depressive symptoms. In three samples of participants, including 149 never-depressed adolescent girls, 41 never-depressed women, and 39 depressed women, we examined whether generally adaptive forms of coping interacted with generally maladaptive forms of coping to predict depressive symptoms. Age-appropriate measures of coping and depression were administered to participants in each sample. In never-depressed females, maladaptive coping/rumination were more strongly related to depressive symptoms in the presence of lower levels of adaptive coping. The relation between depression and maladaptive coping/rumination was weaker in the context of higher levels of adaptive coping. In contrast, for the depressed females, we found main effects for rumination and adaptive coping, with higher levels of rumination and lower levels of adaptive coping being associated with higher levels of depressive symptoms. The present findings highlight how adaptive coping and maladaptive coping, including rumination, differentially relate to each other and depressive symptoms depending on individuals' current depressive state.
View details for DOI 10.1016/j.brat.2010.01.007
View details for Web of Science ID 000278480800002
View details for PubMedID 20211463
Children of depressed mothers are themselves at elevated risk for developing a depressive disorder. We have little understanding, however, of the specific factors that contribute to this increased risk. This study investigated whether never-disordered daughters whose mothers have experienced recurrent episodes of depression during their daughters' lifetime differ from never-disordered daughters of never-disordered mothers in their processing of facial expressions of emotion.Following a negative mood induction, daughters completed an emotion identification task in which they watched faces slowly change from a neutral to a full-intensity happy, sad, or angry expression. We assessed both the intensity that was required to accurately identify the emotion being expressed and errors in emotion identification.Daughters of depressed mothers required greater intensity than did daughters of control mothers to accurately identify sad facial expressions; they also made significantly more errors identifying angry expressions.Cognitive biases may increase vulnerability for the onset of disorders and should be considered in early intervention and prevention efforts.
View details for DOI 10.1111/j.1469-7610.2009.02175.x
View details for Web of Science ID 000276246900006
View details for PubMedID 19788553
View details for Web of Science ID 000277064200704
Previous studies have demonstrated a specific cognitive bias for sad stimuli in currently depressed patients; little is known, however, about whether this bias persists after recovery from the depressive episode. Depression is frequently observed in patients with asthma and is associated with a worse course of the disease. Given these high rates of co-morbidity, we could expect to observe a similar bias towards sad stimuli in patients with asthma.We therefore examined cognitive biases in memory and attention in 20 currently and 20 formerly depressed participants, 20 never-depressed patients diagnosed with asthma, and 20 healthy control participants. All participants completed three cognitive tasks: the self-referential encoding and incidental recall task, the emotion face dot-probe task and the emotional Stroop task.Compared with healthy participants, currently and formerly depressed participants, but not patients with asthma, exhibited specific biases for sad stimuli.These results suggest that cognitive biases are evident in depression even after recovery from an acute episode but are not found in never-depressed patients with asthma.
View details for DOI 10.1017/S0033291709990948
View details for Web of Science ID 000277324500015
View details for PubMedID 19719897
Anticipating a stressor elicits robust cardiovascular and affective responses. Despite the possibility that recovery from these responses may have implications for physical and mental well-being, little research has examined this issue. In this study, participants either gave a public speech or anticipated giving a speech. Compared with speech-givers, participants who anticipated giving a speech, on average, exhibited similar cardiovascular recovery (decreased heart rate [HR] and increased respiratory sinus arrhythmia [RSA]), and reported lower negative affect during recovery. Only in the anticipation condition, however, were cardiovascular recovery and affective recovery associated: poor affective recovery predicted incomplete HR recovery and decreased RSA. These are the first data to compare explicitly recovery from anticipation of a stressor with recovery from the stressor itself. These findings suggest that failing to recover from anticipation has unique physiological costs that, in turn, may contribute to mental and physical illness.
View details for DOI 10.1016/j.biopsycho.2010.01.010
View details for Web of Science ID 000279197500002
View details for PubMedID 20096747
How does culture shape the effects of depression on emotion? A previous study showed that depression dampened negative emotional responses in European Americans, but increased these responses in Asian Americans (Chentsova-Dutton et al., 2007). These findings support the cultural norm hypothesis, which predicts that depression reduces individuals' abilities to react in culturally ideal ways (i.e., disrupting European Americans' abilities to express emotions openly and Asian Americans' abilities to moderate emotions). In the present study, we examined the generalizability of this hypothesis to positive emotion. We measured the emotional reactivity of 35 European Americans (17 depressed) and 31 Asian Americans (15 depressed) to an amusing film. Consistent with the cultural norm hypothesis, European Americans who were depressed showed dampened emotional reactivity (i.e., fewer smiles, less intense reports of positive emotion, lower cardiac activation) compared to control European Americans, whereas Asian Americans who were depressed showed similar (for smiles and reports of positive emotion), and even greater (for higher cardiac activation) emotional reactivity compared to control Asian Americans. These findings suggest that the cultural norm hypothesis generalizes to positive emotion.
View details for DOI 10.1037/a0017562
View details for Web of Science ID 000277174200021
View details for PubMedID 20438167
Deficits in reward processing and their neural correlates have been associated with major depression. However, it is unclear if these deficits precede the onset of depression or are a consequence of this disorder.To determine whether anomalous neural processing of reward characterizes children at familial risk for depression in the absence of a personal history of diagnosable disorder.Comparison of neural activity among children at low and high risk for depression as they process reward and loss.University functional magnetic resonance imaging facility.Thirteen 10- to 14-year-old never-disordered daughters of mothers with recurrent depression ("high risk") and 13 age-matched never-disordered daughters with no family history of depression ("low risk"). Main Outcome Measure Neural activity, as measured using functional magnetic resonance imaging, in key reward and attention neural circuitry during anticipation and receipt of reward and loss.While anticipating gains, high-risk participants showed less activation than did their low-risk counterparts in the putamen and left insula but showed greater activation in the right insula. When receiving punishment, high-risk participants showed greater activation in the dorsal anterior cingulate gyrus than did low-risk participants, who showed greater activation in the caudate and putamen.Familial risk for depression affects neural mechanisms underlying the processing of reward and loss; young girls at risk for depression exhibit anomalies in the processing of reward and loss before the onset of depressive symptoms. Longitudinal studies are needed to examine whether these characteristics predict the subsequent onset of depression.
View details for Web of Science ID 000276312800008
View details for PubMedID 20368513
To test whether the BDNF gene interacts with exercise to predict depressive symptoms. Physical activity is associated with a range of positive health outcomes, including fewer depressive symptoms. One plausible mechanism underlying these findings involves Brain-Derived Neurotrophic Factor (BDNF), a protein hypothesized to limit or repair the damage caused by stress. Physical activity increases expression of BDNF, which may enhance brain health. BDNF expression is controlled by the BDNF gene. Compared with individuals without a BDNF met allele, met-allele carriers have a lower expression of BDNF, which has been associated with Major Depressive Disorder.Eighty-two healthy adolescent girls were genotyped for the BDNF val66met polymorphism, and their depressive symptoms and physical activity were assessed using questionnaires.BDNF genotype, Children's Depression Inventory, and the Physical Activity Questionnaire for Older Children and Adolescents.The BDNF polymorphism was found to moderate the relation between exercise and depressive symptoms: being physically active was protective for girls with a BDNF met allele (fewer depressive symptoms) but not for girls with the val/val polymorphism.By integrating psychological and biological factors, the present study enhances our understanding of how physical activity contributes to resilience to psychopathology.
View details for DOI 10.1037/a0017261
View details for Web of Science ID 000276135800005
View details for PubMedID 20230085
In two experiments, we investigated individual differences in the ability to resolve interference in participants diagnosed with major depressive disorder (MDD). Participants were administered the "Ignore/Suppress" task, a short-term memory task composed of two steps. In Step 1 ("ignore"), participants were instructed to memorize a set of stimuli while ignoring simultaneously presented irrelevant material. In Step 2 ("suppress"), participants were instructed to forget a subset of the previously memorized material. The ability to resolve interference was indexed by response latencies on two recognition tasks in which participants decided whether a probe was a member of the target set. In Step 1, we compared response latencies to probes from the to-be-ignored list with response latencies to nonrecently presented items. In Step 2, we compared response latencies to probes from the to-be-suppressed list with response latencies to nonrecently presented items. The results indicate that, compared with control participants, depressed participants exhibited increased interference in the "suppress" but not in the "ignore" step of the task, when the stimuli were negative words. No group differences were obtained when we presented letters instead of emotional words. These findings indicate that depression is associated with difficulty in removing irrelevant negative material from short-term memory.
View details for DOI 10.3758/CABN.10.1.21
View details for Web of Science ID 000282066600003
View details for PubMedID 20233953
Researchers have documented that the hippocampus is smaller in individuals with depression than in those without. The temporal or causal association of this reduction in hippocampal volume in depression, however, is not known.To test the hypothesis that reduced hippocampal volume precedes and therefore may be implicated in the onset of depression.We used magnetic resonance imaging to examine brain structure volume in individuals at high and low familial risk of depression. Anatomic images from magnetic resonance imaging were analyzed using both whole-brain voxel-based morphometry and manual tracing of the bilateral hippocampus.A research university.Fifty-five girls aged between 9 and 15 years: 23 daughters of mothers with recurrent episodes of depression in the daughter's lifetime (high risk) and 32 age-matched daughters of mothers with no history of psychopathology (low risk). None of the girls had any past or current Axis I psychopathology.Group differences in voxel-based morphometry brain matter density estimates and traced hippocampal volume.Voxel-based morphometry analyses indicated that individuals at high risk of depression had significantly less gray matter density in clusters in the bilateral hippocampus (P < .001) than low-risk participants. Tracing yielded a volumetric reduction in the left hippocampus in the high-risk participants (P < .05).Compared with individuals at low familial risk of the development of depression, high-risk individuals have reduced hippocampal volume, indicating that neuroanatomic anomalies associated with depression may precede the onset of a depressive episode and influence the development and course of this disorder.
View details for Web of Science ID 000275042900007
View details for PubMedID 20194827
Relational peer victimization is associated with internalizing symptoms. Compared to boys, girls are more likely to be both relationally victimized by peers and distressed by the victimization. While previous studies have reported that a functional polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) moderates the effect of stressful life events on depressive symptoms, the present study is the first to evaluate the interaction of this polymorphism with relational peer victimization to predict level of depressive symptoms in young girls.Participants were 78 girls ages 10 to 14 who had no current or past Axis I disorder. Girls were genotyped for 5-HTTLPR; peer victimization was assessed with the Social Experiences Questionnaire, and depressive symptoms with the Children's Depression Inventory.The 5-HTTLPR polymorphism alone did not predict level of depressive symptoms; the interaction of 5-HTTLPR and relational peer victimization, however, was a significant predictor of depressive symptoms. Follow-up analyses indicated that peer victimization significantly predicted level of depressive symptoms only for girls who were homozygous for the short allele, and not for girls homozygous for the long allele or who were heterozygous for the short and long alleles.The findings support the diathesis-stress model of depression: having two 5-HTTLPR short alleles confers vulnerability to depressive symptoms in adolescent girls when they experience relational peer victimization. These findings also suggest that relational peer victimization, at least for girls with genetic vulnerability, is a significant source of stress and should be recognized in the monitoring and prevention of bullying.
View details for DOI 10.1111/j.1469-7610.2009.02149.x
View details for Web of Science ID 000273310800007
View details for PubMedID 19754661
The present study used functional magnetic resonance imaging to examine neural correlates of inhibitory dysfunction in individuals diagnosed with major depressive disorder (MDD). Twelve MDD participants and 12 never-depressed controls completed the negative affective priming (NAP) task in the scanner. Results indicated that, in depressed participants, increased activation in the rostral anterior cingulate cortex (rACC) is associated with inhibition of negative, but not positive, words; in contrast, in nondepressed participants, inhibition of positive, but not negative, words is associated with increased activation in the rACC. These findings indicate that abnormalities in neural function, especially in the rACC, may underlie difficulties experienced by depressed individuals in inhibiting negative thoughts. These results underscore the importance of continuing to examine the relation between cognitive and neural functioning in depression in order to gain a broader and more integrative understanding of this disorder.
View details for DOI 10.1016/j.pscychresns.2009.07.010
View details for Web of Science ID 000274423000005
View details for PubMedID 19962859
Despite the fact that emotions involve multiple time-varying components, little is known about the underlying neural basis of these temporal dynamics. In this paper, we assess these temporal dynamics by using time-varying hemodynamic response functions (HRF) to model BOLD responses to emotional stimuli. We show that these time-varying HRFs lead to a better fit to the BOLD data and yield larger areas of significant activation than do conventional gamma-based canonical HRFs. We also report for the first time that intensity of emotional experience is associated with both magnitude and duration of brain activation. Specifically, greater negative emotional intensity was associated with greater magnitude of activation in the occipital cortex and with longer duration of activation in regions along the cortical midline associated with self-referent processing: the anterior medial prefrontal cortex and the posterior cingulate cortex. These data significantly advance our understanding of how the brain processes emotion and suggest that the intensity of a negative emotional experience is due in part to elaborative self-referent processing that is captured by the duration of neural activity in cortical midline structures. These data also underscore the importance of using modeling techniques that will help elucidate the chronometry of both normal and psychopathological emotional processes.
View details for DOI 10.1016/j.neuroimage.2009.10.006
View details for Web of Science ID 000272808400053
View details for PubMedID 19833213
Depression is a disorder of impaired emotion regulation. Consequently, examining individual differences in the habitual use of emotion regulation strategies has considerable potential to inform models of this debilitating disorder. The aim of the current study was to identify cognitive processes that may be associated with the use of emotion regulation strategies and to elucidate their relation to depression. Depression has been found to be associated with difficulties in cognitive control and, more specifically, with difficulties inhibiting the processing of negative material. We used a negative affective priming task to assess the relations among inhibition and individual differences in the habitual use of rumination, reappraisal, and expressive suppression in clinically depressed, formerly depressed, and never-depressed participants. We found that depressed participants exhibited the predicted lack of inhibition when processing negative material. Moreover, within the group of depressed participants, reduced inhibition of negative material was associated with greater rumination. Across the entire sample, reduced inhibition of negative material was related to less use of reappraisal and more use of expressive suppression. Finally, within the formerly depressed group, less use of reappraisal, more use of rumination, and greater expressive suppression were related to higher levels of depressive symptoms. These findings suggest that individual differences in the use of emotion regulation strategies play an important role in depression, and that deficits in cognitive control are related to the use of maladaptive emotion regulation strategies in this disorder.
View details for DOI 10.1080/02699930903407948
View details for Web of Science ID 000274980700007
View details for PubMedID 20300538
Cognitive theories of depression posit that people's thoughts, inferences, attitudes, and interpretations, and the way in which they attend to and recall information, can increase their risk for depression. Three mechanisms have been implicated in the relation between biased cognitive processing and the dysregulation of emotion in depression: inhibitory processes and deficits in working memory, ruminative responses to negative mood states and negative life events, and the inability to use positive and rewarding stimuli to regulate negative mood. In this review, we present a contemporary characterization of depressive cognition and discuss how different cognitive processes are related not only to each other, but also to emotion dysregulation, the hallmark feature of depression. We conclude that depression is characterized by increased elaboration of negative information, by difficulties disengaging from negative material, and by deficits in cognitive control when processing negative information. We discuss treatment implications of these conclusions and argue that the study of cognitive aspects of depression must be broadened by investigating neural and genetic factors that are related to cognitive dysfunction in this disorder. Such integrative investigations should help us gain a more comprehensive understanding of how cognitive and biological factors interact to affect the onset, maintenance, and course of depression.
View details for DOI 10.1146/annurev.clinpsy.121208.131305
View details for Web of Science ID 000277906700012
View details for PubMedID 20192795
A specific polymorphism of the brain-derived neurotrophic factor (BDNF) gene is associated with alterations in brain anatomy and memory; its relevance to the functional connectivity of brain networks, however, is unclear. Given that altered hippocampal function and structure has been found in adults who carry the methionine (met) allele of the BDNF gene and the molecular studies elucidating the role of BDNF in neurogenesis and synapse formation, we examined the association between BDNF gene variants and neural resting connectivity in children and adolescents. We observed a reduction in hippocampal and parahippocampal to cortical connectivity in met-allele carriers within both default-mode and executive networks. In contrast, we observed increased connectivity to amygdala, insula and striatal regions in met-carriers, within the paralimbic network. Because of the known association between the BDNF gene and neuropsychiatric disorder, this latter finding of greater connectivity in circuits important for emotion processing may indicate a new neural mechanism through which these gene-related psychiatric differences are manifest. Here we show that the BDNF gene, known to regulate synaptic plasticity and connectivity in the brain, affects functional connectivity at the neural systems level. In addition, we demonstrate that the spatial topography of multiple high-level resting state networks in healthy children and adolescents is similar to that observed in adults.
View details for DOI 10.3389/neuro.09.055.2009
View details for Web of Science ID 000274619300004
View details for PubMedID 19956404
Depression is characterized by a range of cognitive deficits that theorists posit are due to the resource capturing properties of rumination. The present study was designed to examine the relation between rumination and resource allocation in depression. Twenty-five depressed and 25 nondepressed participants completed a modified dual-task version of the recency-probes task, which assesses the controlled allocation of cognitive resources by comparing performance across low- and high-interference conditions. In low-interference conditions, participants performed either the recency-probes task or a tracking task, which required participants to track specific stimuli across trials (i.e., no dual-task interference). In the high-interference condition, participants performed both the recency-probes task and the tracking task, which required the controlled allocation of resources to resolve dual-task interference. Depressed participants performed significantly worse than did their nondepressed counterparts in only the high-interference condition; performance of the 2 groups was comparable in the low-interference conditions. Furthermore, the degree to which depressed participants were impaired in the high-interference condition was correlated .74 with rumination. These findings suggest that an association between rumination and impairments in resource allocation underlies the cognitive difficulties experienced by depressed individuals.
View details for DOI 10.1037/a0017206
View details for Web of Science ID 000271669100007
View details for PubMedID 19899845
This study investigated the identification of facial expressions of emotion in currently nondepressed participants who had a history of recurrent depressive episodes (recurrent major depression; RMD) and never-depressed control participants (CTL). Following a negative mood induction, participants were presented with faces whose expressions slowly changed from neutral to full intensity. Identification of facial expressions was measured by the intensity of the expression at which participants could accurately identify whether faces expressed happiness, sadness, or anger. There were no group differences in the identification of sad or angry expressions. Compared with CTL participants, however, RMD participants required significantly greater emotional intensity in the faces to correctly identify happy expressions. These results indicate that biases in the processing of emotional facial expressions are evident even after individuals have recovered from a depressive episode.
View details for DOI 10.1037/a0016944
View details for Web of Science ID 000271669100014
View details for PubMedID 19899852
Levels of extra-synaptic dopamine in the brain vary as a function of polymorphisms at the val158met locus of the catechol-O-methyltransferase (COMT) gene. In vivo studies of this polymorphism in the human brain have typically measured patterns of neural activation during dopamine-mediated tasks in adults. This study is the first to investigate the effects of COMT on brain physiology during rest and in children. We used flow-sensitive arterial spin-labeling (ASL) magnetic resonance imaging to examine brain blood flow (CBF) in 42 children. Compared with val-allele carriers, met-allele homozygotes exhibited greater CBF in mesolimbic, mesocortical, and nigrostriatal dopamine (DA) pathways. Higher CBF in DA-rich brain structures reflects COMT-related baseline differences that (1) underlie the selective behavioral advantages associated with each genotype; (2) affect interpretations of previously reported genotype differences in BOLD signal changes; and (3) serve as a foundation for future studies on the effects of COMT on brain development.
View details for DOI 10.1016/j.neuroimage.2009.05.076
View details for Web of Science ID 000269321100025
View details for PubMedID 19500679
A growing body of research suggests that the ability to regulate emotion remains stable or improves across the adult life span. Socioemotional selectivity theory maintains that this pattern of findings reflects the prioritization of emotional goals. Given that goal-directed behavior requires attentional control, the present study was designed to investigate age differences in selective attention to emotional lexical stimuli under conditions of emotional interference. Both neural and behavioral measures were obtained during an experiment in which participants completed a flanker task that required them to make categorical judgments about emotional and nonemotional stimuli. Older adults showed interference in both the behavioral and neural measures on control trials but not on emotion trials. Although older adults typically show relatively high levels of interference and reduced cognitive control during nonemotional tasks, they appear to be able to successfully reduce interference during emotional tasks.
View details for DOI 10.1037/a0016952
View details for Web of Science ID 000269933600001
View details for PubMedID 19739908
Low perceived social acceptance is a significant risk factor for emotional difficulties in children. No studies, however, have examined genetic factors that may underlie individual differences in perceived social acceptance. In the present study we examined the relation between polymorphisms on the catechol-O-methyltransferase (COMT) Val158Met and serotonin transporter promoter (5-HTTLPR) genes and perceived social acceptance in 103 adolescent girls. Only the COMT polymorphism was related to perceived social acceptance: Val-allele carriers reported greater perceived social acceptance than did homozygous Met-allele carriers. In a subsample of these participants, homozygous Val-allele carriers reported greater maintenance of positive emotions during stress. This, in turn, predicted social acceptance, suggesting that COMT exerts its effects on social functioning through emotion regulation. These data are the first to show an association between COMT and social functioning in children. Future research might profitably examine emotion regulation as a mediator between COMT and social acceptance.
View details for DOI 10.1089/cap.2008.0141
View details for Web of Science ID 000269231100007
View details for PubMedID 19702491
Major Depressive Disorder (MDD) is one of the most prevalent and costly of all psychiatric disorders. The hypothalamic pituitary adrenal (HPA)-axis, which regulates the hormonal response to stress, has been found to be disrupted in depression. HPA dysregulation may represent an important risk factor for depression. To examine a possible genetic underpinning of this risk factor without the confound of current or lifetime depression, we genotyped 84 never-disordered young girls, over a third of whom were at elevated risk for depression, to assess the association between a polymorphism in the promoter region of the serotonin transporter (5-HTT) gene and diurnal variation in HPA-axis activity. This 5-HTT-linked polymorphic region (5-HTTLPR) has been previously found to interact with stress to increase risk for depression. We found 5-HTTLPR to be significantly associated with diurnal cortisol levels: girls who were homozygous for the short-allele had higher levels of waking (but not afternoon or evening) cortisol than did their long-allele counterparts. This finding suggests that genetic susceptibility to HPA-axis dysregulation, especially apparent in levels of waking cortisol, is detectable in individuals as young as 9 years of age.
View details for DOI 10.1016/j.psyneuen.2008.11.006
View details for Web of Science ID 000265953900005
View details for PubMedID 19128885
Previous research has demonstrated that induced sad mood is associated with increased accuracy of recall in certain memory tasks; the effects of clinical depression, however, are likely to be quite different. The authors used the Deese-Roediger-McDermott paradigm to examine the impact of clinical depression on erroneous recall of neutral and/or emotional stimuli. Specifically, they presented Deese-Roediger-McDermott lists that were highly associated with negative, neutral, or positive lures and compared participants diagnosed with major depressive disorder and nondepressed control participants on the accuracy of their recall of presented material and their false recall of never-presented lures. Compared with control participants, major depressive disorder participants recalled fewer words that had been previously presented but were more likely to falsely recall negative lures; there were no differences between major depressive disorder and control participants in false recall of positive or neutral lures. These findings indicate that depression is associated with false memories of negative material.
View details for DOI 10.1037/a0015621
View details for Web of Science ID 000265893300015
View details for PubMedID 19413415
A hallmark characteristic of depression is the inability to regulate the effect of emotional material on cognition. Previous research has demonstrated that depressed individuals are less able than are nondepressed persons to expel irrelevant negative information from working memory (WM), thereby exacerbating the effects of negative content on cognition. The primary goal of this study was to examine whether depressed individuals are also impaired at selecting relevant positive content in the context of representations competing for resources in WM; such an impairment would limit depressed persons' ability to use positive material to ameliorate the cognitive effects of negative information.We administered a Recency-probes task with neutral, positive, and negative words to 20 currently depressed and 22 never-depressed participants. This task assesses the selection of relevant content in WM by inducing interference between current and prior representations of a stimulus in WM. Reaction times to interference and noninterference trials were compared across valence and group to assess how effectively depressed individuals select task-relevant emotional content to resolve interference.Compared to never-depressed controls, depressed individuals were impaired in selecting task-relevant positive stimuli; the performance of the two groups was comparable for selecting task-relevant neutral and negative stimuli.Findings indicate that a valence-specific deficit in WM may contribute to the inability of depressed individuals to regulate emotion, and provide empirical support for formulations that implicate positive insensitivity in the maintenance of depression.
View details for DOI 10.1002/da.20565
View details for Web of Science ID 000265874300003
View details for PubMedID 19347861
View details for Web of Science ID 000265144200020
Major life events and chronic difficulties have been found to be associated with the onset of depression. Little is known, however, about how exposure to such stressors is related to the clinical presentation of this disorder. We addressed this issue by administering an interview-based measure of life stress, the Beck Depression Inventory, and the Global Assessment of Functioning scale to 100 adults diagnosed with major depressive disorder. Participants who experienced a preonset severe life event exhibited greater overall levels of depression severity, endorsed more cognitive and somatic symptoms of depression, and functioned at lower levels than did their counterparts without preonset severe life events. In contrast, exposure to a preonset severe difficulty was unrelated to participants' severity of depression, cognitive and somatic symptoms, or level of global functioning. These findings highlight the potentially greater importance of acute stress compared with chronic stress for influencing these key clinical features of depression.
View details for DOI 10.1097/NMD.0b013e318199f77b
View details for Web of Science ID 000264263300002
View details for PubMedID 19282680
In this study, the authors investigated whether training participants to use cognitive strategies can aid forgetting in depression. Participants diagnosed with major depressive disorder (MDD) and never-depressed participants learned to associate neutral cue words with a positive or negative target word and were then instructed not to think about the negative targets when shown their cues. The authors compared 3 different conditions: an unaided condition, a positive-substitute condition, and a negative-substitute condition. In the substitute conditions, participants were instructed to use new targets to keep from thinking about the original targets. After the training phase, participants were instructed to recall all targets when presented with the cues. MDD participants, in contrast with control participants, did not exhibit forgetting of negative words in the unaided condition. In both the negative and positive substitute conditions, however, MDD participants showed successful forgetting of negative words and a clear practice effect. In contrast, negative substitute words did not aid forgetting by the control participants. These findings suggest that training depressed individuals to use cognitive strategies can increase forgetting of negative words.
View details for DOI 10.1037/a0013794
View details for Web of Science ID 000263369700005
View details for PubMedID 19222312
A forced-choice intensity judgment task was used to investigate biases in the processing of subtle expressions of emotion in participants with major depressive disorder (MDD). Participants were presented with 2 pictures of the same actor side by side, either depicting a neutral and a subtle emotional expression or depicting a subtle positive and a subtle negative expression. Participants were asked to indicate which of the 2 pictures showed the stronger emotion. Compared with participants with social anxiety disorder (SAD) and with never-disordered controls (CTLs), participants with MDD were less likely to judge subtle happy expressions as more intense than neutral expressions. In addition, compared with the CTL participants, participants who had MDD and participants who had SAD were less likely to judge subtle happy expressions to be more intense than negative expressions. Biases in the judgment of the intensity of subtle expressions of positive affect could play an important role in the interpersonal difficulties that are associated with depression.
View details for DOI 10.1037/a0014658
View details for Web of Science ID 000263369700021
View details for PubMedID 19222328
View details for Web of Science ID 000263610700004
Research has consistently documented that depressed individuals process information in a negatively biased manner. There is little evidence, however, concerning whether these biases represent risk factors for depression, as is hypothesized by cognitive models. In the present study we investigated whether a particular cognitive bias observed in currently depressed individuals, the tendency to interpret ambiguous information negatively, characterizes daughters of depressed mothers, a population known to be at increased risk for depression. Following a negative mood induction, young daughters of depressed and never-disordered mothers completed two information-processing tasks in which their interpretations of emotionally ambiguous stimuli were evaluated. Daughters of depressed mothers interpreted ambiguous words more negatively and less positively, and ambiguous stories more negatively, than did daughters of never-disordered mothers. These results provide support for cognitive vulnerability models of depression.
View details for DOI 10.1007/s10802-008-9259-z
View details for Web of Science ID 000262672800006
View details for PubMedID 18679791
View details for Web of Science ID 000270262600005
Previous brain-imaging studies have reported that major depressive disorder (MDD) is characterized by decreased volumes of several cortical and subcortical structures, including the hippocampus, amygdala, anterior cingulate cortex, and caudate nucleus. The purpose of the present study was to identify structural volumetric differences between MDD and healthy participants using a method that allows a comparison of gray and white matter volume across the whole brain. In addition, we explored the relation between symptom severity and brain regions with decreased volumes in MDD participants. The study group comprised 22 women diagnosed with MDD and 25 healthy women with no history of major psychiatric disorders. Magnetic resonance brain images were analyzed using optimized voxel-based morphometry to examine group differences in regional gray and white matter volume. Compared with healthy controls, MDD participants were found to have decreased gray matter volume in the bilateral caudate nucleus and the thalamus. No group differences were found for white matter volume, nor were there significant correlations between gray matter volumes and symptom severity within the MDD group. The present results suggest that smaller volume of the caudate nucleus may be related to the pathophysiology of MDD and may account for abnormalities of the cortico-striatal-pallido-thalamic loop in MDD.
View details for DOI 10.1016/j.pscychresns.2007.12.020
View details for Web of Science ID 000261551600003
View details for PubMedID 18930633
Major depressive disorder has been associated with volumetric abnormality in the amygdala. In this meta-analysis we examine results from magnetic resonance imaging volumetry studies of the amygdala in depression in order to assess both the nature of the relationship between depression and amygdala volume as well as the influence of extraexperimental factors that may account for significant variability in reported findings. We searched PubMed and ISI Web of Knowledge databases for articles published from 1985 to 2008 that used the wildcard terms 'Depress*' and 'Amygdal*' in the title, keywords or abstract. From the 13 studies that met inclusion criteria for our meta-analysis, we calculated aggregate effect size and heterogeneity estimates from amygdala volumetric data; we then used meta-regression to determine whether variability in specific extraexperimental factors accounted for variability in findings. The lack of a reliable difference in amygdala volume between depressed and never-depressed individuals was accounted for by a positive correlation between amygdala volume differences and the proportion of medicated depressed persons in study samples: whereas the aggregate effect size calculated from studies that included only medicated individuals indicated that amygdala volume was significantly increased in depressed relative to healthy persons, studies with only unmedicated depressed individuals showed a reliable decrease in amygdala volume in depression. These findings are consistent with a formulation in which an antidepressant-mediated increase in levels of brain-derived neurotrophic factor promotes neurogenesis and protects against glucocorticoid toxicity in the amygdala in medicated but not in unmedicated depression.
View details for DOI 10.1038/mp.2008.57
View details for Web of Science ID 000260632200002
View details for PubMedID 18504424
The regions that comprise the functionally connected resting-state default-mode network (DMN) in adults appear to be the same as those that are characterized by task-induced decreases in blood-oxygen-level-dependent (BOLD) signal. Independent component analysis can be used to produce a picture of the DMN as an individual rests quietly in the scanner. Contrasts across conditions in which cognitive load is parametrically modulated can delineate neural structures that have decreases in activation in response to high-demand task conditions. Examination of the degree to which these networks subsume dissociable brain substrates, and of the degree to which they overlap, provides insight concerning their purpose, function, and the nature of their associations. Few studies have examined the DMN in children, and none have tested whether the neural regions that comprise the DMN during a resting condition are the same regions that show reduced activity when children engage in cognitive tasks. In this paper we describe regions that show both task-related decreases and spontaneous intrinsic activity at rest in children, and we examine the co-localization of these networks. We describe ways in which the DMN in 7-12-year-old children is both similar to and different from the DMN in adults; moreover, we document that task-induced deactivations and default-mode resting-state activity in children share common neural substrates. It appears, therefore, that even before adolescence a core aspect of task-induced deactivation involves reallocating processing resources that are active at rest. We describe how future studies assessing the development of these systems would benefit from examining these constructs as part of one continuous system.
View details for DOI 10.1016/j.neuroimage.2008.03.029
View details for Web of Science ID 000256620400029
View details for PubMedID 18482851
Although memory biases for negatively valenced stimuli have been reliably associated with depression and have been postulated to play a critical role in the maintenance of this disorder, the neural bases of these biases have received little attention. In this study, we tested a model of heightened memory sensitivity for negative information in depression in which neural mechanisms that normally facilitate memory for affective material are over-recruited during encoding of negative material in depression.We used functional magnetic resonance imaging to examine amygdala activity and functional connectivity with the hippocampus and caudate-putamen during successful encoding--as assessed by a recognition memory probe 1 week after scanning--of negative, neutral, and positive pictures by 14 depressed and 12 nondepressed individuals.Depressed individuals demonstrated greater memory sensitivity than nondepressed participants to negative but not to neutral or positive stimuli. The right amygdala was more active and showed greater functional connectivity with the hippocampus and caudate-putamen in depressed than in control participants during encoding of subsequently remembered negative but not neutral or positive stimuli. The degree of memory-related right amygdala responsivity in the depressed participants was significantly correlated with depressive severity.These findings support the formulation that, in remembering negative information better than nondepressed persons, depressed individuals over-recruit a neural network involved more generally in enhancing memory for affective stimuli and that the degree to which they over-recruit this system is related to the severity of clinical symptomatology.
View details for DOI 10.1016/j.biopsych.2007.12.015
View details for Web of Science ID 000256491700009
View details for PubMedID 18281017
Recent evidence indicates that individuals who are homozygous for the short (s) allele in the promoter region of the serotonin transporter gene have higher rates of depression and other psychiatric disorders as a function of exposure to increasing levels of stressful life events than do individuals who have one or two copies of the long (l) allele. Despite the reliability of this association, the mechanism by which this polymorphism confers risk for psychopathology in the presence of stress is not understood. This study was designed to examine the formulation that individuals who are homozygous for the s allele are characterized by a greater biological reactivity to stress than are their counterparts who have one or two copies of the l allele.Girls at high (n = 25) and low (n = 42) risk for depression by virtue of the presence or absence of a family history of this disorder were genotyped and exposed to a standardized laboratory stress task. Cortisol levels were assessed before the stressor, after the stressor, and during an extended recovery period.Girls who were homozygous for the s allele produced higher and more prolonged levels of cortisol in response to the stressor than did girls with an l allele.These findings indicate that the 5-HTTLPR polymorphism is associated with biological stress reactivity, which may increase susceptibility to depression in the face of stressful life events.
View details for DOI 10.1016/j.biopsych.2007.10.008
View details for Web of Science ID 000254945400005
View details for PubMedID 18005940
Two experiments examined the link between interpretation and memory in individuals diagnosed with Generalized Social Phobia (GSP). In Experiment 1, GSP and control participants generated continuations for nonsocial and ambiguous social scenarios. GSP participants produced more socially anxious and negative continuations for the social scenarios than did the controls. On the subsequent test of recalling the social scenarios, intrusion errors that shared meaning with the original continuations were made more frequently by the GSP group, producing false recall with emotionally negative features. To examine whether nonanxious individuals would also produce such errors if given emotional interpretations, in Experiment 2 the authors asked university students to read the scenarios plus endings produced by GSP participants in Experiment 1. The students either constructed vivid mental images of themselves as the main characters or thought about whether the endings provided closure. Low-anxious students in the closure condition produced fewer ending-based intrusions in recalling the social scenarios than did students in the other 3 conditions. Results illustrate the importance of examining the nature of source-monitoring errors in investigations of memory biases in social anxiety.
View details for DOI 10.1037/0021-843X.117.2.278
View details for Web of Science ID 000255671500003
View details for PubMedID 18489204
Reduced responsiveness to positive incentives is a central feature of Major Depressive Disorder (MDD). In the present study, we compared neural correlates of monetary incentive processing in unmedicated depressed participants and never-depressed control subjects.Fourteen currently depressed and 12 never-depressed participants underwent functional magnetic resonance imaging while participating in a monetary incentive delay task. During the task, participants were cued to anticipate and respond to a rapidly presented target to gain or avoid losing varying amounts of money.Depressed and never-depressed participants did not differ in nucleus accumbens (NAcc) activation or in affective or behavioral responses during gain anticipation. Depressed participants did, however, exhibit increasing anterior cingulate activation during anticipation of increasing gains, whereas never-depressed participants showed increasing anterior cingulate activation during anticipation of increasing loss. Depressed participants also showed reduced discrimination of gain versus nongain outcomes.The present findings indicate that although unmedicated depressed individuals have the capacity to experience positive arousal and recruit NAcc activation during gain anticipation, they also exhibit increased anterior cingulate cortex activation, suggestive of increased conflict during anticipation of gains, in addition to showing reduced discrimination of gain versus nongain outcomes.
View details for DOI 10.1016/j.biopsych.2007.07.023
View details for Web of Science ID 000254107100008
View details for PubMedID 17916330
View details for Web of Science ID 000254163700235
View details for Web of Science ID 000254807700019
The ability to regulate one's mood state effectively is critical to emotional and physical health. Recent investigations have sought to delineate the neural mechanisms by which individuals regulate mood states and emotions, positing a critical role of a dorsal system that includes the dorsolateral prefrontal cortex and anterior cingulate. This study extended these efforts by examining the neural correlates of retrieving positive autobiographical memories while experiencing a negative mood state in a sample of healthy female adults. We demonstrated that mood-incongruent recall is associated with activation in ventrolateral and ventromedial prefrontal cortices (including orbitofrontal cortex and subgenual cingulate). These findings suggest that mood-incongruent recall differs from other affect regulation strategies by influencing mood through a ventral regulatory network.
View details for Web of Science ID 000250901700004
View details for PubMedID 18090309
Studies of Western samples (e.g., European Americans [EAs]) suggest that depressed individuals tend to show diminished emotional reactivity (J. G. Gehricke & A. J. Fridlund, 2002; G. E. Schwartz, P. L. Fair, P. Salt, M. R. Mandel, & G. L. Klerman, 1976a, 1976b). Do these findings generalize to individuals oriented to other cultures (e.g., East Asian cultures)? The authors compared the emotional reactions (i.e., reports of emotional experience, facial behavior, and physiological reactivity) of depressed and nondepressed EAs and Asian Americans of East Asian descent (AAs) to sad and amusing films. Their results were consistent with previous findings: Depressed EAs showed a pattern of diminished reactivity to the sad film (less crying, less intense reports of sadness) compared with nondepressed participants. In contrast, depressed AAs showed a pattern of heightened emotional reactivity (greater crying) compared with nondepressed participants. Across cultural groups, depressed and nondepressed participants did not differ in their reports of amusement or facial behavior during the amusing film. Physiological reactivity to the film clips did not differ between depressed and control participants for either cultural group. Thus, although depression may influence particular aspects of emotional reactivity across cultures (e.g., crying), the specific direction of this influence may depend on prevailing cultural norms regarding emotional expression.
View details for DOI 10.1037/0021-843X.116.4.776
View details for Web of Science ID 000250937700010
View details for PubMedID 18020723
Recent research suggests that the recall of positive memories plays an important role in mood regulation. In this study, the authors examined the ability of currently depressed, formerly depressed, and never-depressed participants to regulate sad mood through the recall of positive memories or through distraction. Although improvement in mood was found for all participants in response to distraction, under instructions to recall positive memories, never-depressed participants' moods improved, whereas formerly depressed participants' sad moods remained unchanged. It is important to note that depressed participants exhibited a worsening of their sad moods after recalling positive memories. These results suggest both that depression is associated with an impaired ability to use positive recall to regulate a sad mood and that this impairment continues to be evident following recovery.
View details for DOI 10.1037/0021-843X.116.3.484
View details for Web of Science ID 000248642800005
View details for PubMedID 17696704
A long-standing debate concerns whether dysfunctional cognitive processes and content play a causal role in the etiology of depression or more simply represent correlates of the disorder. There has been insufficient appreciation in this debate of specific predictions afforded by cognitive theory in relation to major life stress and changes in cognition over time. In this paper we present a novel perspective for investigating the etiological relevance of cognitive factors in depression. We hypothesize that individuals who experienced a severe life event prior to the onset of major depression will exhibit greater changes in dysfunctional attitudes over the course of the episode than will individuals without a severe life event.Fifty-three participants diagnosed with major depression were assessed longitudinally, approximately 1 year apart, with state-of-the-art measures of life stress and dysfunctional attitudes.Depressed individuals with a severe life event prior to episode onset exhibited greater changes in cognitive biases over time than did depressed individuals without a prior severe event. These results were especially pronounced for individuals who no longer met diagnostic criteria for major depression at the second assessment.Specific patterns of change in cognitive biases over the course of depression as a function of major life stress support the etiological relevance of cognition in major depression.
View details for DOI 10.1017/S0033291707000281
View details for Web of Science ID 000247050000009
View details for PubMedID 17407615
View details for Web of Science ID 000245698100092
Researchers have documented that children of depressed mothers are at elevated risk for developing a depressive disorder themselves. There is currently little understanding, however, of what factors place these children at elevated risk. In the present study, the authors investigated whether never-disordered daughters whose mothers have experienced recurrent episodes of depression during their daughters' lifetime are characterized by biased processing of emotional information. Following a negative mood induction, participants completed an emotional-faces dot-probe task. Daughters at elevated risk for depression, but not control daughters of never-disordered mothers, selectively attended to negative facial expressions. In contrast, only control daughters selectively attended to positive facial expressions. These results provide support for cognitive vulnerability models of depression.
View details for DOI 10.1037/0021-843X.116.1.135
View details for Web of Science ID 000244162200013
View details for PubMedID 17324024
Major life events have been found to precede onsets of a 1st lifetime episode of depression more commonly than subsequent recurrences. Despite general empirical support for this finding, few data directly address how the role of major life events may change over successive recurrences. Further, little research has examined major chronic difficulties in relation to a 1st lifetime episode versus a recurrence of depression. The present study tested the associations between major life events and major difficulties in relation to lifetime history of depressive episodes in a sample of 96 individuals diagnosed with major depression. Using investigator-based measures of life stress, the authors found that, whereas major life events were associated with fewer lifetime episodes, major chronic difficulties were related to more prior episodes. These findings are discussed in terms of underlying mechanisms that may account for the changing role of major life stress over successive recurrences of depression.
View details for DOI 10.1037/0021-843X.116.1.116
View details for Web of Science ID 000244162200011
View details for PubMedID 17324022
This study was designed to examine whether processing of emotional stimuli predicts both symptomatic improvement and recovery from depression. Participants diagnosed with Major Depressive Disorder (MDD) (N=63) completed information-processing tasks to assess attention to and memory for sad, physically threatening, socially threatening, and happy stimuli. At a follow-up session an average of nine months later, participants were reassessed to determine diagnostic status and depression severity. None of the measure of attention or memory predicted diagnostic status at follow-up. Those depressed participants who remembered a higher proportion of positive words that they had endorsed as self-descriptive exhibited greater symptomatic improvement. After controlling for memory of positive self-referential words, attentional measures did not predict symptomatic change. These results are consistent with a growing literature highlighting the importance of emotionally relevant memory processes for understanding the course of major depression.
View details for DOI 10.1037/1528-3522.214.171.124
View details for Web of Science ID 000244491500018
View details for PubMedID 17352575
This study was designed to examine attentional biases in the processing of emotional faces in currently and formerly depressed participants and healthy controls. Using a dot-probe task, the authors presented faces expressing happy or sad emotions paired with emotionally neutral faces. Whereas both currently and formerly depressed participants selectively attended to the sad faces, the control participants selectively avoided the sad faces and oriented toward the happy faces, a positive bias that was not observed for either of the depressed groups. These results indicate that attentional biases in the processing of emotional faces are evident even after individuals have recovered from a depressive episode. Implications of these findings for understanding the roles of cognitive and interpersonal functioning in depression are discussed.
View details for DOI 10.1037/0021-843X.116.1.80
View details for Web of Science ID 000244162200007
View details for PubMedID 17324018
According to cognitive diathesis-stress theories, a latent cognitive vulnerability to depression is activated by negative affect in individuals at risk for depressive relapse. This vulnerability can manifest as mood-congruent memory during sad mood and may involve amygdala response, which is implicated in memory for emotionally arousing stimuli. This study examined whether amygdala modulates memory for negatively valenced words before and after a sad mood induction in healthy individuals with and without a history of recurrent major depression.Fourteen unmedicated remitted depressed (RD) and 14 matched never depressed (ND) individuals were scanned using functional magnetic resonance imaging (fMRI) while performing a self-referent encoding/evaluation task (SRET) preceding and following a sad mood challenge. After each SRET, participants' free recall was assessed.Following sad mood induction, bilateral amygdala response during encoding of valenced words predicted increased recall of negative self-referent words for a subset of RD participants. This association was not present before the sad mood induction and was not evident in individuals without a history of depression, regardless of mood state.These results are consistent with cognitive diathesis-stress theories and suggest a role for the amygdala in modulating mood-congruent memory during transient sad mood in individuals who are vulnerable to depression relapse.
View details for DOI 10.1016/j.biopsych.2006.05.004
View details for Web of Science ID 000243454900015
View details for PubMedID 16950223
Previous research has suggested that Social Anxiety Disorder (SAD) is associated with a tendency to interpret ambiguous social stimuli in a threatening manner. The present study used event-related functional magnetic resonance imaging to examine patterns of neural activation in response to the processing of neutral facial expressions in individuals diagnosed with SAD and healthy controls (CTLs). The SAD participants exhibited a different pattern of amygdala activation in response to neutral faces than did the CTL participants, suggesting a neural basis for the biased processing of ambiguous social information in SAD individuals.
View details for DOI 10.1016/j.pscychresns.2006.05.003
View details for Web of Science ID 000242668900006
View details for PubMedID 17030117
The present study was designed to examine the operation of depression-specific biases in the identification or labeling of facial expression of emotions. Participants diagnosed with major depression and social phobia and control participants were presented with faces that expressed increasing degrees of emotional intensity, slowly changing from a neutral to a full-intensity happy, sad, or angry expression. The authors assessed individual differences in the intensity of facial expression of emotion that was required for the participants to accurately identify the emotion being expressed. The depressed participants required significantly greater intensity of emotion than did the social phobic and the control participants to correctly identify happy expressions and less intensity to identify sad than angry expressions. In contrast, social phobic participants needed less intensity to correctly identify the angry expressions than did the depressed and control participants and less intensity to identify angry than sad expressions. Implications of these results for interpersonal functioning in depression and social phobia are discussed.
View details for DOI 10.1037/0021-843X.115.4.705
View details for Web of Science ID 000242132400006
View details for PubMedID 17100528
The present study investigated the validity of the two-factor solution of items selected from the Rumination Scale of the Response Style Questionnaire proposed by Treynor, Gonzalez, and Nolen-Hoeksema (2003). In the first part of this study we used samples of currently depressed (MDD), formerly depressed (FD), socially anxious (SP), and healthy control participants to examine whether the brooding and reflective pondering components differentiate participants with an anxiety disorder from participants with depression. In the second part of this study we examined whether these components of rumination were differentially related to cognitive biases in depression. Overall, the MDD group exhibited higher brooding scores than did all other groups; SP and FD groups did not differ from each other but obtained higher brooding scores than did the control participants. Only the MDD and the control groups differed on the reflective pondering factor. Importantly, brooding and reflective pondering were differentially related to cognitive biases. Specifically, the correlation between brooding/reflective pondering and memory bias was not significant when depressive symptoms were partialed out. The correlation between brooding and attentional bias for sad faces, however, remained significant even when current depressive symptoms were taken into account. In sum, our results support the formulation that rumination is composed of an adaptive reflective pondering factor and a maladaptive brooding factor.
View details for Web of Science ID 000248377900007
View details for PubMedID 16942978
Major depression has been associated with anomalous activation in the subgenual anterior cingulate cortex, but its response to emotional stimuli is poorly understood. The primary goal of this study was to compare levels of activation in the subgenual anterior cingulate cortex of diagnosed depressed and nondepressed participants in response to happy and sad facial expressions of affect. Whereas cognitive theories of depression predict increased activation to negative stimuli, depressed participants were found to exhibit increased activation to both types of stimuli in the subgenual anterior cingulate cortex. Importantly, the loci were in different regions of the subgenual anterior cingulate cortex, suggesting that there is functional specialization in the processing of negatively and positively valenced stimuli.
View details for Web of Science ID 000233277700002
View details for PubMedID 16237317
The authors examined intentional forgetting of negative material in depression. Participants were instructed to not think about emotional nouns that they had learned to associate with a neutral cue word. The authors provided participants with multiple occasions to suppress the unwanted words. Overall, depressed participants successfully forgot negative words. Moreover, the authors obtained a clear practice effect. However, forgetting came at a cost: Compared with the nondepressed participants and with the depressed participants who were instructed to forget positive words, depressed participants who were instructed to forget negative words showed significantly worse recall of the baseline words. These results indicate that training depressed individuals in intentional forgetting could prove to be an effective strategy to counteract automatic ruminative tendencies and mood-congruent biases.
View details for DOI 10.1037/0021-843X.114.4.640
View details for Web of Science ID 000233760700015
View details for PubMedID 16351371
The present study tested 3 competing views of how depression alters emotional reactivity: positive attenuation (reduced positive), negative potentiation (increased negative), and emotion context insensitivity (ECI; reduced positive and negative). Normative and idiographic stimuli that elicited happy, sad, and neutral states were presented to currently depressed, formerly depressed, and healthy control individuals while experiential, behavioral, and autonomic responses were measured. Currently depressed individuals reported less sadness reactivity and less happiness experience across all conditions than did the other participants, and they exhibited a more dysphoric response to idiographic than to normative stimuli. Overall, data provide partial support for the positive attenuation and ECI views. Depression may produce mood-state-dependent changes in emotional reactivity that are most pronounced in emotion experience reports.
View details for DOI 10.1037/0021-843X.114.4.627
View details for Web of Science ID 000233760700014
View details for PubMedID 16351385
Behavioral studies suggest that emotional reactivity in depressed persons predicts subsequent symptom reduction. Using functional magnetic resonance imaging in a prospective study, we show that greater amygdala activation to emotional facial expressions among depressed patients predicts symptom reduction 8 months later, controlling for initial depression severity and medication status. Functional magnetic resonance imaging may thus be used as a method to identify neural markers in depressed patients at risk for poor outcome.
View details for Web of Science ID 000231492600003
View details for PubMedID 16056122
Given the chronic and recurrent nature of major depressive disorder (MDD), it is important to understand whether specific symptoms are stable over time or vary over the course of the disorder. This is the first longitudinal investigation examining the stability of the nine criterion symptoms of depression, as specified in the DSM-IV, among diagnosed depressed adults who were not recovered at follow-up. In this study, participants were assessed twice, ten months apart, with the structured clinical interview for DSM-IV, and stability of the nine criterion symptoms of MDD was examined. Findings indicate strong stability in individuals' symptom profiles. Among individuals who were clinically depressed at both assessments, there were no statistically significant fluctuations in specific symptoms endorsed. Changes in symptom endorsement among individuals who no longer met diagnostic criteria for MDD at Time 2 were attributable to reduced severity (i.e., number of symptoms) rather than to inconsistency of symptom endorsement. These results indicate that depressed individuals experience essentially the same pattern of specific symptoms over the course of a year. Variation in clinical course is likely to be attributable more to fluctuations in overall severity than to changes in specific symptoms of depression.
View details for DOI 10.1016/j.jpsychires.2004.11.001
View details for Web of Science ID 000230295900010
View details for PubMedID 15804392
Cardiac vagal tone, as indexed by abnormalities in the level and/or reactivity of respiratory sinus arrhythmia (RSA), has been related to psychiatric impairment, including risk for depression. Longitudinal studies of depression have focused on RSA levels and have found mixed support for the hypothesis that low RSA levels predict a more pernicious course of depression. The current investigation focuses on the relation between RSA reactivity and the course of depression. We measured depressed persons' RSA reactivity to sadness-, fear-, and amusement-inducing emotion films and reassessed participants' diagnostic status 6 months later. Depressed persons who exhibited a higher degree of vagal withdrawal to the sad film were more likely to recover from depression. Implications for the study of RSA in depression are discussed.
View details for DOI 10.1111/j.1469-8986.2005.00289.x
View details for Web of Science ID 000229666500004
View details for PubMedID 15943681
Although children of bipolar parents are at heightened risk for developing emotional disorders, the processes underlying this vulnerability are not well understood. This study examined biases in the processing of emotional stimuli as a potential vulnerability marker of bipolar disorder.Sixteen children of bipolar parents who did not show any indication of having an emotional disorder at the time of testing and ten children of never-disordered control parents underwent a negative mood induction designed to activate cognitive schemas and were then administered an emotion Stroop task and a self-referent encoding task.Children of bipolar parents were found to exhibit an attentional bias towards social-threat and manic-irritable words. Furthermore, although high- and low-risk children did not differ in their endorsement of positive and negative words as self-descriptive, the high-risk children demonstrated better recall of negative words than did the low-risk children.Thus, children without a mood disorder who are at high risk for developing a mood disorder were found to exhibit biases in attention and memory that are similar to those found for bipolar and unipolar depressed adults, suggesting that children at increased risk for affective disorder are characterized by potentially pathogenic cognitive structures that can be activated by sad mood. These findings offer insights into mechanisms of cognitive vulnerability for bipolar disorders.
View details for Web of Science ID 000226637500008
View details for PubMedID 15660646
View details for Web of Science ID 000227878701237
Depression involves either enhanced processing of negative stimuli or diminished processing of positive stimuli. We used functional magnetic resonance imaging to assess brain activation in depressed vs healthy participants. Fifteen participants diagnosed with major depressive disorder and 15 controls were scanned during a lexical decision task involving neutral, happy, sad, and threat-related words. For happy words, depressed subjects exhibited less activation than did controls to happy words in fronto-temporal and limbic regions. For sad words, depressed subjects showed more activation than did controls in the inferior parietal lobule and less activation in the superior temporal gyrus and cerebellum, suggesting a complex activation pattern that varies for neural sub-circuits that may be associated with different cognitive or behavioral processes.
View details for Web of Science ID 000226068600005
View details for PubMedID 15570157
Research has not resolved whether depression is associated with a distinct information-processing bias, whether the content of the information-processing bias in depression is specific to themes of loss and sadness, or whether biases are consistent across the tasks most commonly used to assess attention and memory processing. In the present study, participants diagnosed with major depression, social phobia, or no Axis I disorder, completed several information-processing tasks assessing attention and memory for sad, socially threatening, physically threatening, and positive stimuli. As predicted, depressed participants exhibited specific biases for stimuli connoting sadness; social phobic participants did not evidence such specificity for threat stimuli. It is important to note that the different measures of bias in memory and attention were not systematically intercorrelated. Implications for the study of cognitive bias in depression, and for cognitive theory more broadly, are discussed.
View details for DOI 10.1037/0021-843x.113.3.386
View details for Web of Science ID 000223137900003
View details for PubMedID 15311984
An information-processing paradigm was used to examine attentional biases in clinically depressed participants, participants with generalized anxiety disorder (GAD), and nonpsychiatric control participants for faces expressing sadness, anger, and happiness. Faces were presented for 1000 ms, at which point depressed participants had directed their attention selectively to depression-relevant (i.e., sad) faces. This attentional bias was specific to the emotion of sadness; the depressed participants did not exhibit attentional biases to the angry or happy faces. This bias was also specific to depression; at 1000 ms, participants with GAD were not attending selectively to sad, happy, or anxiety-relevant (i.e., angry) faces. Implications of these findings for both the cognitive and the interpersonal functioning of depressed individuals are discussed and directions for future research are advanced.
View details for PubMedID 14992665
To study the possible role of the amygdala in the recognition of happy and sad facial expressions in adolescents aged 13 to 17 years.Twelve healthy adolescents (6 females and 6 males) underwent noninvasive 3-Tesla functional magnetic resonance imaging while viewing pictures of happy, sad, and neutral facial expressions.Happy faces produced significant bilateral amygdalar activation when compared with neutral faces (p <.05, corrected). Sad faces relative to neutral did not produce significant amygdalar activation.These results extend the role of the amygdala in adolescents to include the recognition of happy facial expressions. They demonstrate the feasibility of using happy facial expressions to noninvasively study amygdalar function in adolescents and establish a baseline against which the amygdalar response to emotional stimuli in several psychiatric conditions may be compared.
View details for DOI 10.1097/01.CHI.0000046886.27264.BA
View details for Web of Science ID 000184302700016
View details for PubMedID 12874501
The authors examined whether adolescent major depressive disorder (MDD) was associated with difficulties in young adult functioning and whether differences would remain significant after accounting for nonmood disorder, MDD recurrence, functioning in adolescence, or current mood state. A total of 941 participants were assessed twice during adolescence and at age 24. In unadjusted analyses, adolescent MDD was associated with most young adult functioning measures. Associations were not due to interactions with adolescent comorbidity, but differences in global functioning and mental health treatment appeared as a result of MDD recurrence. Accounting for levels of functioning in adolescence or for current depression at age 24 eliminated the remaining associations. The implications of these findings for efforts to prevent MDD in adolescence are discussed.
View details for DOI 10.1037/0021-843X.112.3.353
View details for Web of Science ID 000184624000003
View details for PubMedID 12943014
Recent reviews of cognitive theories of depression have noted that individualized assessment strategies might help to resolve mixed findings regarding the stability of depressotypic beliefs and attitudes. We describe encouraging results for an individualized measure of one such cognitive construct, irrational beliefs. Twenty depression-prone women (recurrent major depressives in full remission) and twenty closely matched never-depressed controls completed leading forced-choice measures of irrational beliefs (the Belief Scale; BS) and sociotropy-autonomy (The Revised Personal Style Inventory), as well as the Specific Demands on Self Scale (SDS). The BS requires participants to rate their agreement with twenty preselected statements of irrational beliefs, while the SDS focuses on whether participants harbor any strongly held irrational beliefs, even if uncommon or idiosyncratic. Consistent with previous research, there were no group differences on the traditional measure of irrational beliefs. In contrast, depression-prone participants strongly exceeded controls on the SDS, and this difference persisted after controlling for residual depression, anxiety symptoms, anxiety diagnoses, sociotropy, and autonomy. These findings provide some initial support for a key assumption of the rational-emotive model of depression, and, more broadly, suggest that individualized assessment strategies may help researchers capture the core negative beliefs of asymptomatic individuals, even in the absence of mood or cognitive priming.
View details for DOI 10.1002/jclp.10081
View details for Web of Science ID 000181750000004
View details for PubMedID 12652636
Respiratory sinus arrhythmia (RSA) is an index of the vagal control of heart rate that is associated with emotion regulatory capacity. To examine RSA in depressed and nondepressed participants in the context of an emotion-regulatory challenge, we presented a sad film to induce crying, a behavior associated with heightened parasympathetic activation. We predicted that nondepressed persons who cried would show elevations in RSA during the onset and the resolution of crying. By contrast, we predicted that depressed individuals who cried would fail to exhibit increased RSA over the course of their crying episodes. As hypothesized, nondepressed participants exhibited RSA increases that accompanied the resolution of tearful crying, consistent with a homeostatic function for crying, whereas depressed subjects who cried did not exhibit increased RSA. Results suggest that the physiological self-regulatory mechanisms invoked by crying are compromised in depression.
View details for Web of Science ID 000180455300001
View details for PubMedID 12751799
Theorists have proposed that depression is associated with abnormalities in the behavioral activation (BAS) and behavioral inhibition (BIS) systems. In particular, depressed individuals are hypothesized to exhibit deficient BAS and overactive BIS functioning. Self-reported levels of BAS and BIS were examined in 62 depressed participants and 27 nondepressed controls. Clinical functioning was assessed at intake and at 8-month follow-up. Relative to nondepressed controls, depressed participants reported lower BAS levels and higher BIS levels. Within the depressed group, lower BAS levels were associated with greater concurrent depression severity and predicted worse 8-month outcome. Levels of both BIS and BAS showed considerable stability over time and clinical state. Overall, results suggest that BAS dysregulation exacerbates the presentation and course of depressive illness.
View details for DOI 10.1037//0021-843X.111.4.589
View details for Web of Science ID 000178941600006
View details for PubMedID 12428772
Most theories of amygdalar function have underscored its role in fear. One broader theory suggests that neuronal activation of the amygdala in response to fear-related stimuli represents only a portion of its more widespread role in modulating an organism's vigilance level. To further explore this theory, the amygdalar response to happy, sad, angry, fearful, and neutral faces in 17 subjects was characterized using 3 T fMRI. Utilizing a random effects model and hypothesis-driven analytic strategy, it was observed that each of the four emotional faces was associated with reliable bilateral activation of the amygdala compared with neutral. These findings suggest a broader role for the amygdala in modulating the vigilance level during the perception of several negative and positive facial emotions.
View details for Web of Science ID 000179156600009
View details for PubMedID 12395114
Research findings based on the retrospective reports of depressed individuals have long been held suspect because of possible negative reporting biases associated with depression. In the present study we assess the stability of retrospective reports of past traumatic events, past depressive episodes, parental depression, and parental substance abuse in a sample of 234 adults whose depression status changed over two assessments conducted one year apart. Depression status was found to affect reporting of number of past depressive episodes and past traumatic events, but not reporting of parental psychopathology. Implications of these findings are discussed for research that relies on the retrospective self-reports of depressed participants.
View details for Web of Science ID 000179297000004
View details for PubMedID 12467255
Respiratory sinus arrhythmia (RSA) is a noninvasive measure of parasympathetic tone that has been related to emotion regulatory capacity. While some previous work indicates that clinically depressed persons exhibit lower levels of RSA than do normal controls, there is nevertheless considerable between-subject variation in RSA among depressed persons. The current study evaluated the significance of variation in RSA among depressed persons by examining whether levels of RSA predicted concurrent symptomatology and the course of depressive illness.The RSA levels of 55 diagnosed depressed individuals were assessed during a paced breathing procedure at Time 1. Six months later (Time 2), participants were interviewed again to determine whether or not each had fully recovered from depression. Multinomial regression analyses were conducted to examine whether RSA predicted Time 2 clinical status.Although RSA levels were not related to overall depression severity, they were associated with specific symptoms of depression: RSA was positively associated with the report of sadness and negatively associated with the report of suicidality. More strikingly, however, higher levels of RSA at Time 1 predicted non-recovery from depression at Time 2, even when statistically controlling for initial depression severity, age and medication use.Treatment and medication use were not controlled during the follow-up period and a group of nonpsychiatric controls was not included in this study.A relatively high level of RSA among depressed individuals predicts a more pernicious course of illness than do lower RSA levels.
View details for Web of Science ID 000177824700033
View details for PubMedID 12167527
Depressed individuals often fail to react to emotionally significant stimuli. The significance of this pattern of emotional dysregulation in depression is poorly understood. In the present study, depressed and nondepressed participants viewed standardized neutral, sad, fear, and amusing films; and experiential, behavioral, and physiological responses to each film were assessed. Compared with nondepressed controls, depressed participants reported sadness and amusement in a flattened, context-insensitive manner. Those depressed participants who reported the least reactivity to the sad film exhibited the greatest concurrent impairment. Prospectively, the depressed participant who exhibited the least behavioral and heart rate reactivity to the amusing film were the least likely to recover from depression. Loss of the context-appropriate modulation of emotion in depression may reflect a core feature of emotion dysregulation in this disorder.
View details for DOI 10.1037//1528-35126.96.36.199
View details for Web of Science ID 000208224500004
View details for PubMedID 12899187
Clinical lore suggests that depression is associated with frequent and intense crying. To test these postulations empirically, a standardized cry-evoking stimulus was presented to depressed and nondepressed participants, and their likelihood of crying and the magnitude of crying-related changes in their emotion experience, behavior, and autonomic physiology were compared. Unexpectedly, crying was no more likely in depressed than in nondepressed participants. Within the nondepressed group, participants who cried exhibited increases in the report and display of sadness and had greater cardiac and electrodermal activation than did participants who did not cry. There was less evidence of this crying-related emotional activation within the depressed group. The lack of emotional activation among clinically depressed participants who cried provides a tantalizing clue concerning how emotions are dysregulated in this disorder.
View details for DOI 10.1037//0021-843X.111.2.302
View details for Web of Science ID 000175078600009
View details for PubMedID 12003451
View details for Web of Science ID 000085051900008
View details for Web of Science ID 000167657700007
To examine the importance of chronologic age versus pubertal status in predicting adolescent girls' depressive symptoms in different ethnic groups.A national probability sample was used to obtain a representative cohort of 3216 adolescents, 5th through 8th grades. Subjects completed a questionnaire, which included a modified version of the Children's Depression Inventory (CDI) and an assessment of timing of menarche.Among Caucasians, post-menarcheal adolescent girls had higher depression scores than did same-aged pre-menarcheal girls. Boys and pre-menarcheal girls had similar depression scores in most age groups. Among African-Americans and Hispanics, there were no menarche-associated differences in depressive symptoms.In early adolescence pubertal status is a better predictor of depressive symptoms than chronological age in Caucasian, but not African-American or Hispanic girls.
View details for Web of Science ID 000081723700008
View details for PubMedID 10447041
Differential risk factors for the onset of depression were prospectively examined in a community-based sample of adolescents (N = 1,709), some of whom had a history of major depressive disorder (MDD; n = 286) and some of whom did not (n = 1,423). From the theories of J. Teasdale (1983, 1988) and R. Post (1992) concerning the etiology of initial versus recurrent episodes of depression, the authors hypothesized that (a) dysphoric mood and dysfunctional thinking styles would be correlated more highly among those with a previous history of MDD than among those without a history of MDD; (b) dysphoric mood or symptoms and dysfunctional thinking would be a stronger predictor of onset of recurrent episodes (n = 43) than of first onsets (n = 70); and (c) major life stress would be a stronger predictor of first onsets of MDD than of recurrent episodes. The results provide support for the 3 hypotheses and suggest that distinct processes are involved in the onset of first and recurrent episodes of MDD.
View details for Web of Science ID 000082120000013
View details for PubMedID 10466272
To determine: (a) what demographic and psychosocial factors are associated with elevated levels of depressive symptoms in adolescence; (b) whether girls and boys show different profiles of correlates and probable risk factors for depressive symptoms; and (c) what the implications are of these results for future research directions and policy decisions.Using a nationally representative sample of adolescent school students in Grades 5-12, the Commonwealth Fund Adolescent Health Survey assessed depressive symptoms as well as a number of variables posited to be risk factors and correlates of depression.Depressive symptoms were found to differ by gender, age, socioeconomic status, and ethnicity. In addition, life stress, social support, and coping were associated with depressive symptoms. Importantly, stress and social support appear to be particularly salient aspects of depression among girls. Both physical and sexual abuse were strongly linked with depression for both boys and girls, with sexual abuse having a stronger impact among boys. Finally, high levels of depressive symptoms were associated with increased use of both mental and physical health care resources among boys and girls.The correlates of depression in this adolescent sample closely resemble those seen in adult samples, including demographic and psychosocial variables. Some psychosocial variables, such as stress and social support, may have a greater impact on depressive symptoms for girls than for boys. Results of this study also have important implications for the health care system, given that higher levels of depressive symptoms were found to be associated with greater utilization of physical health care resources.
View details for Web of Science ID 000081723700004
View details for PubMedID 10447037
In previous studies, depression has been associated with both marital status and marital distress. Unfortunately, given the cross-sectional design of most of this research, the temporal nature of these associations is unclear. The authors examined the marital functioning of young adults as a function of whether they received psychiatric diagnoses of major depressive disorder or nonaffective psychiatric disorder during adolescence. Depression during adolescence was found to predict higher rates of marriage among younger women and subsequent marital dissatisfaction. This pattern of results appears to be specific to depression: The presence during adolescence of a nonaffective psychiatric disorder was unrelated to subsequent marital functioning. These findings highlight the potentially adverse consequences of depression in adolescence and underscore the importance of prevention and early treatment efforts.
View details for Web of Science ID 000076987000016
View details for PubMedID 9830257
View details for Web of Science ID 000077693800006
View details for Web of Science ID 000077148300002
View details for Web of Science ID 000075747000007
Gender differences in anxiety were examined in a large sample of adolescents that included 1,079 who had never met criteria for any disorder, 95 who had recovered from an anxiety disorder, and 47 who had a current anxiety disorder. Participants were examined on a wide array of psychosocial measures. There was a preponderance of females among current and recovered anxiety disorder cases, but not among those who had never experienced an anxiety disorder. The female preponderance emerges early in life, and retrospective data indicate that at age 6, females are already twice as likely to have experienced an anxiety disorder than are males. Psychosocial variables that were correlated with both anxiety and gender were identified. Statistically controlling for these variables did not eliminate the gender differences in prevalence or anxiety symptom means.
View details for Web of Science ID 000072029400010
View details for PubMedID 9505043
View details for Web of Science ID 000071456200006
Recent studies have found that temporal variability and reactivity in self-esteem (SE) are associated with risk for depressive symptoms subsequent to life stress. It is unclear, however, whether it is variability uniquely in SE that is critical, or whether variability in other domains, such as specific self-evaluation (SSE) and affect, would show similar effects. Further, the specificity of these effects to depression is unknown. In the present study, initially nondepressed women completed 7 daily ratings of SE, SSE, and affect. Over a 6-week prospective interval, the interactions of stressful life events and variability in both SE and SSE predicted changes in depression, particularly in individuals with more severe worst lifetime episodes of depressive symptoms. These effects were independent of average level of SE and SSE, as well as neuroticism and self-concept uncertainty. In contrast, variability in affect failed to predict changes in depression in interaction with life stress. Finally, none of the predictor variables interacted with stressful life events in predicting changes in anxiety.
View details for Web of Science ID A1997YD32900003
View details for PubMedID 9358682
View details for Web of Science ID A1997YG51300003
Although the psychosocial difficulties associated with adolescent depression are relatively well known, the extent to which these problems are specific to depression has received little attention. The authors examined the specificity to depression of a wide range of psychosocial variables in the following 3 groups of adolescents: depressed cases (n = 48), nonaffective disorder cases (n = 92), and never mentally ill participants (n = 1,079). The authors found 3 of the 44 variables assessed in this study to be strongly specific to depression, and only the depressed participants exhibited more problematic functioning than did the never mentally ill controls. Three variables are as follows: self-consciousness, self-esteem, and a reduction in activities because of physical illness or injury. Eight variables were more strongly associated with depression than with nonaffective disorder, and 8 variables characterized both depressed and nonaffective disorder adolescents. Implications of these findings for psychosocial theories of depression are discussed.
View details for Web of Science ID A1997XM16100002
View details for PubMedID 9241938
The roles of gender, early childhood loss and personality as risk factors for lifetime episodes of dysphoria were examined in a large sample of college students (N = 557). Dysphoria classifications were based on the Inventory to Diagnose Depression (IDD) and the IDD-Lifetime Version. Brief dysphoria was defined as meeting DSM-III-R symptom criteria for major depression without meeting the two-week duration criteria, whereas protracted dysphoria required that the duration criteria were also met. Although females reported higher levels of depressive symptoms and neuroticism than did males, and were more likely to have a lifetime history of episodes of dysphoria, males were more susceptible to the adverse effects of early childhood loss. Males with loss were more likely to have a history of protracted dysphoria and to report higher levels of neuroticism than were males who did not experience an early parental loss. Neuroticism, in turn, acted as a trait vulnerability characteristic to episodes of dysphoria in both males and females. Interestingly, the effects of gender on lifetime experience of dysphoria were mediated by neuroticism: females' increased vulnerability to episodes of dysphoria was due to their elevated levels of neuroticism.
View details for Web of Science ID A1997WZ72700003
View details for PubMedID 9167861
View details for Web of Science ID A1997WH20800004
The goals of this study were: (a) to determine which among a set of depression-related psychosocial variables are state-dependent; (b) to examine whether state-trait distinctions among psychosocial variables are a function of gender; and (c) to test the hypothesis that state-dependence of psychosocial variables is mostly evident in people with a history of clinical depression. Altogether, 562 participants residing in two communities completed a battery of psychosocial measures at point of entry into the study (T1) and after an average interval of 8.3 months (T2). The state-dependence of psychosocial variables was examined in two groups of participants: (a) low-high (LH: those who were low on the Center for Epidemiologic Studies Depression Scale at T1 and high at T2; N = 45); and (b) high-low (HL: those who were high at T1 and low at T2; N = 64). The following variables were found to be state-dependent: engagement in pleasant and unpleasant events; frequency of social contacts; dissatisfaction with oneself, one's neighborhood dwelling and one's friends; irrational beliefs, and positive and negative expectancies. In contrast, the following variables were not state-dependent: dissatisfaction with family and job, perception of control, and external attributions for positive and negative events. State-dependence was not moderated by age, gender or a history of depression. Possible explanations for why some variables are state-dependent and others are not state-dependent are offered.
View details for Web of Science ID A1996VH73500002
View details for PubMedID 8889076
Three studies investigated the relation between adult attachment security and symptoms of depression. Study l examined the overall magnitude of the association between adult attachment and depression, and Studies 2 and 3 tested whether this relation was mediated by dysfunctional attitudes and low self-esteem. Results from the three studies were consistent with a mediation model. This model suggests that insecure adult attachment styles are associated with dysfunctional attitudes, which in turn predispose to lower levels of self-esteem. Such depletions in self-esteem are directly associated with increases in depressive symptoms over time. Insecure attachment appears to lead to depressive symptoms in adulthood through its impact on self-worth contingencies and self-esteem.
View details for Web of Science ID A1996TW05000009
View details for PubMedID 8636884
To determine the specificity to major depressive disorder (MDD) of a wide array of psychosocial risk factors in older adolescents (aged 14 through 18 years).Diagnostic and psychosocial assessments were conducted with 1,507 randomly selected high school students at T1 and after approximately 1 year (T2). Three diagnostic groups were compared: those who had an episode of MDD during that year (n = 90), those who had an episode of substance use disorder during that year (SUD) (n = 42), and a control group with no disorder (n = 1,189).Risk factors specific to MDD were stress (minor and major events), emotional reliance, physical symptoms and disease, history of suicide attempt, and a past episode of depression or anxiety disorder. Risk factors specific to SUD were tobacco use, academic difficulties, and a past episode of SUD. Risk factors that were shared were current depression symptoms, internalizing and externalizing behavior problems, coping skills, interpersonal conflict with parents, and dissatisfaction with grades.By determining the number of risk factors for MDD, for SUD, or those that are general to both disorders, clinicians can make informed predictions concerning the probable future onset of a full-fledged episode of MDD and/or SUD in individual cases. The results of this study allow for the identification of adolescents who are at elevated risk for MDD and SUD. The results also have implications for the design of interventions aimed at preventing the occurrence of these disorders. Such interventions should target change on risk factors of the type identified in this study.
View details for Web of Science ID A1995RR32300021
View details for PubMedID 7559318
View details for Web of Science ID A1995RJ69300010
In studies of clinical depression, individuals who demonstrate elevated levels of symptoms but do not meet interview-based diagnostic criteria are typically labeled as false positive and eliminated from further consideration. However, the implicit assumption that false-positive participants differ in important ways from true-positive (i.e., diagnosed) participants has not been tested systematically. This study compared the functioning of true-positive, false-positive, and true-negative adolescents on clinical and psychosocial functioning. Although the false-positive participants manifested higher levels of current and future psychopathology than did the true-negative participants, they did not differ significantly from the true-positive participants on most of the measures of psychosocial dysfunction. "False positive," therefore, is not a benign condition.
View details for Web of Science ID A1995QG93600012
View details for PubMedID 7896995
In a prospective study of adolescent depression, adolescents (N = 1,508) were assessed at Time 1 and after 1 year (Time 2) on psychosocial variables hypothesized to be associated with depression. Most psychosocial variables were associated with current (n = 45) depression. Formerly depressed adolescents (n = 217) continued to differ from never depressed controls on many of the psychosocial variables. Many of the depression-related measures also acted as risk factors for future depression (n = 112), especially past depression, current other mental disorders, past suicide attempt, internalizing behavior problems, and physical symptoms. Young women were more likely to be, to become, and to have been depressed. Controlling for the psychosocial variables eliminated the gender difference for current and future but not for past depression.
View details for Web of Science ID A1994NL11100014
View details for PubMedID 8040500
Despite recent findings that the prevalence of unipolar depression is as high in adolescents as it is in adults, relatively little is known about the applicability of cognitive theories of depression to adolescents. The present study examined the nature, specificity, and stability of cognitive dysfunction in male and female depressed, remitted, and psychiatric control adolescents. Factor analysis of a diverse set of measures yielded two factors, labelled Negative Cognitions and Attributional Style. Scores on both these factors were related to a current diagnosis of depression. Results also indicated that there may not be complete recovery of cognitive functioning (or of depressed mood) with diagnostic remission of depression. Finally, whereas elevated scores on the Negative Cognitions factor appeared to be specific to depression, the depressed and psychiatric control adolescents did not differ with respect to their scores on the Attributional Style factor.
View details for Web of Science ID A1993MF71900014
View details for PubMedID 8282931