Impact of cognitive profile on social functioning in prepubescent females with Turner syndrome
2013; 19 (2): 161-172
Aberrant neurocognitive processing of fear in young girls with Turner syndrome.
Social cognitive and affective neuroscience
Social deficits are prevalent in Turner syndrome (TS); however, the extent to which these difficulties are secondary to characteristic cognitive impairments is not well known. Here, we sought to establish the relative contribution of executive functions, visuospatial abilities, and IQ to social difficulties in young girls with TS. Forty TS girls and 19 typically developing (TD) children were assessed with the Social Responsiveness Scale (SRS), the Motor-Free Visual Spatial Test (MVPT-3), the Behavior Rating Inventory of Executive Function (BRIEF), and an IQ test. Hierarchical multiple regression analyses were conducted with the SRS subscales as outcome variables. In a first step, the cognitive factors were entered (verbal IQ, BRIEF global score, MVPT-3, and age), followed by the group variable in a second step. In comparison to TD, TS participants were significantly impaired on all main measures. All six regression models with the SRS subscales were significant and revealed that global executive functions explained the largest portion of the variance on all subscales and the total score. Even after controlling for cognitive elements, the group factor still explained a significant portion of the variance of the Social Cognition, Social Awareness, and Autistic Mannerisms subscales. In contrast, the group factor was not a significant predictor of Social Motivation and Social Communication scores. These results suggest that executive dysfunctions play a role in social impairments encountered in TS, but also that some specific aspects of social behavior are altered beyond what can be attributed to cognitive difficulties in this population.
View details for DOI 10.1080/09297049.2011.647900
View details for Web of Science ID 000315675600004
View details for PubMedID 22372383
White Matter Aberrations in Prepubertal Estrogen-Naive Girls with Monosomic Turner Syndrome
2012; 22 (12): 2761-2768
Appraisal of fearful stimuli is an integral aspect of social cognition. Neural circuitry underlying this phenomenon has been well-described and encompasses a distributed network of affective and cognitive nodes. Interestingly, this ability to process fearful faces is impaired in Turner syndrome (TS), a genetic disorder of females in which all or part of an X chromosome is missing. However, neurofunctional correlates for this impairment have not been well-studied, particularly in young girls. Given that the core features of TS include X chromosome gene haploinsufficiency and secondary sex hormone deficiencies, investigation of fearful face processing may provide insights into the influence of X chromosome gene expression on this network. Therefore, we examined behavioral and neural responses during an explicit emotional face labeling task in 14 prepubertal girls with TS and 16 typically developing age-matched controls (6-13 years). We demonstrate that girls with TS have a specific impairment in the identification of fearful faces and show decreased activation in several cognitive control regions, including the anterior dorsal anterior cingulate cortex, dorsolateral prefrontal cortex and posterior cingulate gyrus. Our results indicate that aberrant functional activation in dorsal cognitive regions plays an integral role in appraisal of, and regulation of response to fear in TS.
View details for PubMedID 23171616
Cognition and behavior in Turner syndrome: a brief review.
Pediatric endocrinology reviews : PER
2012; 9: 710-712
Turner syndrome (TS) offers a unique opportunity to investigate associations among genes, the brain, and cognitive phenotypes. In this study, we used 3 complementary analyses of diffusion tensor imaging (DTI) data (whole brain, region of interest, and fiber tractography) and a whole brain volumetric imaging technique to investigate white matter (WM) structure in prepubertal, nonmosaic, estrogen-naive girls with TS compared with age and sex matched typically developing controls. The TS group demonstrated significant WM aberrations in brain regions implicated in visuospatial abilities, face processing, and sensorimotor and social abilities compared with controls. Extensive spatial overlap between regions of aberrant WM structure (from DTI) and regions of aberrant WM volume were observed in TS. Our findings indicate that complete absence of an X chromosome in young females (prior to receiving exogenous estrogen) is associated with WM aberrations in specific regions implicated in characteristic cognitive features of TS.
View details for DOI 10.1093/cercor/bhr355
View details for Web of Science ID 000310965200005
View details for PubMedID 22172580
Genomic Imprinting Effects on Cognitive and Social Abilities in Prepubertal Girls with Turner Syndrome
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
2012; 97 (3): E460-E464
There is increasing evidence that Turner syndrome is associated with a distinct pattern of cognitive and neurophysiological characteristics. Typically this has been characterized by relative strengths in verbal skills, contrasting with relative weaknesses in arithmetic, visuospatial and executive function domains. Potential differences in social cognitive processing have also been identified. More recently, applications of neuroimaging techniques have further elucidated underlying differences in brain structure, function and connectivity in individuals with Turner syndrome. Ongoing research in this area is focused on establishing a unified mechanistic model incorporating genetic influences from the X chromosome, sex hormone contributions, neuroanatomical variation and differences in cognitive processes. This review broadly covers current understanding of how X-monosomy impacts neurocognitive phenotype both from the perspective of cognitive-behavioral and neuroimaging studies. Furthermore, relevant clinical aspects of identifying potential learning difficulties and providing anticipatory guidance for affected individuals with TS, are briefly discussed.
View details for PubMedID 22946281
Aberrant functional network recruitment of posterior parietal cortex in turner syndrome.
Human brain mapping
Recent evidence suggests that the cognitive and social manifestations associated with Turner syndrome (TS) might be influenced by epigenetic factors in the form of genomic imprinting. However, due to small and heterogeneous samples, inconsistent results have emerged from these studies.The objective of this prospective study was to establish the impact of genomic imprinting on neurocognitive abilities and social functioning in young girls with TS.An extensive battery of neuropsychological assessments was administered to 65 children with TS who had never been exposed to estrogen treatment, 24 of whom had an X-chromosome from paternal origin (Xpat) and 41 from maternal origin (Xmat).The Wechsler scales of intelligence, the Motor-Free Visual Spatial test-3, the Wide Range Assessment of Visual Motor Ability, and the attention/executive domain of the NEPSY were used to assess cognitive abilities. Social functioning was assessed with the Social Responsiveness Scale and the Behavior Assessment System for Children-2.Results showed that although individuals with Xpat obtained lower scores than their counterparts with Xmat on most cognitive and social measures, only the Perceptual Reasoning Index of the intelligence scale yielded significant differences after correction for multiple comparisons.Overall, these results suggest that although some aspects of the neuropsychological profile of TS may be influenced by epigenetic factors, the sociocognitive phenotype associated with the disorder is not modulated by genomic imprinting.
View details for DOI 10.1210/jc.2011-2916
View details for Web of Science ID 000301229600020
View details for PubMedID 22238395
Contribution of Executive Functions to Visuospatial Difficulties in Prepubertal Girls With Turner Syndrome
2011; 36 (8): 988-1002
Turner syndrome is a genetic disorder caused by the complete or partial absence of an X chromosome in affected women. Individuals with TS show characteristic difficulties with executive functions, visual-spatial and mathematical cognition, with relatively intact verbal skills, and congruent abnormalities in structural development of the posterior parietal cortex (PPC). The functionally heterogeneous PPC has recently been investigated using connectivity-based clustering methods, which sub-divide a given region into clusters of voxels showing similar structural or functional connectivity to other brain regions. In the present study, we extended this method to compare connectivity-based clustering between groups and investigate whether functional networks differentially recruit the PPC in TS. To this end, we parcellated the PPC into sub-regions based on temporal correlations with other regions of the brain. fMRI data were collected from 15 girls with TS and 14 typically developing (TD) girls, aged 7-14, while they performed a visual-spatial task. Temporal correlations between voxels in the PPC and a set of seed regions were calculated, and the PPC divided into clusters of voxels showing similar connectivity. It was found that in general the PPC parcellates similarly in TS and TD girls, but that regions in bilateral inferior parietal lobules, and posterior right superior parietal lobule, were reliably recruited by different networks in TS relative to TD participants. These regions showed weaker correlation in TS with a set of regions involved in visual processing. These results suggest that abnormal development of visuospatial functional networks in TS may relate to the well documented cognitive difficulties in this disorder. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
View details for PubMedID 22711287
Reduced Functional Connectivity during Working Memory in Turner Syndrome
2011; 21 (11): 2471-2481
Turner syndrome (TS) is a genetic disorder caused by the absence of one X-chromosome in females. Individuals with TS often demonstrate a cognitive profile characterized by poor visuospatial abilities, which may in part be due to executive function impairments. Here, we assessed the neuropsychological profile of 36 prepubertal girls with TS and 20 typically developing children to examine the relationship between executive function and visuospatial abilities. Multiple linear regression analyses revealed that executive functions were closely associated with visuospatial abilities in TS but not in controls. These results suggest that executive dysfunctions observed in TS contribute to their visuospatial impairments.
View details for DOI 10.1080/87565641.2011.584356
View details for Web of Science ID 000296931600003
View details for PubMedID 22004020
Psychosocial Functioning and Social Cognitive Processing in Girls with Turner Syndrome
JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS
2011; 32 (7): 512-520
Turner syndrome (TS) is a genetic disorder affecting females, resulting from the complete or partial absence of an X chromosome. The cognitive profile of TS shows relative strengths in the verbal domain and weaknesses in the procedural domain, including working memory. Neuroimaging studies have identified differences in the morphology of the parietal lobes, and white matter pathways linking frontal and parietal regions, as well as abnormal activation in dorsal frontal and parietal regions. Taken together these findings suggest that abnormal functional connectivity between frontal and parietal regions may be related to working memory impairments in TS, a hypothesis we tested in the present study. We scanned TS and typically developing participants with functional magnetic resonance imaging while they performed visuospatial and phonological working memory tasks. We generated a seed region in parietal cortex based on structural differences in TS and found that functional connectivity with dorsal frontal regions was reduced during working memory in TS. Finally, we found that connectivity was correlated with task performance in TS. These findings suggest that structural brain abnormalities in TS affect not only regional activity but also the functional interactions between regions and that this has important consequences for behavior.
View details for DOI 10.1093/cercor/bhr017
View details for Web of Science ID 000295413200005
View details for PubMedID 21441396
Neuroanatomical spatial patterns in Turner syndrome
2011; 55 (2): 439-447
Turner syndrome (TS) is a common genetic disorder caused by partial or complete absence of the second X chromosome in females and is associated with a characteristic neurocognitive profile traditionally described by discrepancy between verbal and performance IQ. Difficulties in social functioning have also been increasingly identified in this population. The purpose of this study was to examine elements of social competence and cognition in a pre-estrogen population of girls with TS.The authors administered psychosocial and neurocognitive measures to examine metrics of social function and intelligence in a group of young girls with TS, pre-estrogen treatment (n = 42) and control peers (n = 32), aged between 3 and 12 years.Girls with TS demonstrated significantly decreased social competency on all dimensions of the Social Responsiveness Scale, with the exception of the Social Motivation subscale, where ratings were comparable with typically developing peers. Performance on social cognitive tasks was also impaired on NEPSY Memory for Faces and Theory of Mind tasks. Differences were further observed on Behavioral Assessment Scales for Children subscales of Hyperactivity, Atypicality, Attention, Social Skills, Activities of Daily Living, and Functional Communication. Group differences in social cognition or behavior remained significant after adjusting for verbal IQ.This study supports the hypothesis that young girls with TS who have not yet received estrogen treatment demonstrate significantly impaired social cognition. Improved understanding of differences in social competence and cognition can increase awareness and inform clinical approaches to identifying and treating social difficulties in individuals with TS.
View details for DOI 10.1097/DBP.0b013e3182255301
View details for Web of Science ID 000294421200004
View details for PubMedID 21743350
COGNITIVE PROFILE OF TURNER SYNDROME
DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS
2009; 15 (4): 270-278
Turner syndrome (TS) is a highly prevalent genetic condition caused by partial or complete absence of one X-chromosome in a female and is associated with a lack of endogenous estrogen during development secondary to gonadal dysgenesis. Prominent cognitive weaknesses in executive and visuospatial functions in the context of normal overall IQ also occur in affected individuals. Previous neuroimaging studies of TS point to a profile of neuroanatomical variation relative to age and sex matched controls. However, there are no neuroimaging studies focusing on young girls with TS before they receive exogenous estrogen treatment to induce puberty. Information obtained from young girls with TS may help to establish an early neural correlate of the cognitive phenotype associated with the disorder. Further, univariate analysis has predominantly been the method of choice in prior neuroimaging studies of TS. Univariate approaches examine between-group differences on the basis of individual image elements (i.e., a single voxel's intensity or the volume of an a priori defined brain region). This is in contrast to multivariate methods that can elucidate complex neuroanatomical profiles in a clinical population by determining the pattern of between-group differences from many image elements evaluated simultaneously. In this case, individual image elements might not be significantly different between groups but can still contribute to a significantly different overall spatial pattern. In this study, voxel-based morphometry (VBM) of high-resolution magnetic resonance images was used to investigate differences in brain morphology between 13 pediatric, pre-estrogen girls with monosomic TS and 13 age-matched typically developing controls (3.0 T imaging: mean age 9.1±2.1). A similar analysis was performed with an older cohort of 13 girls with monosomic TS and 13 age-matched typically developing controls (1.5 T imaging: mean age 15.8±4.5). A multivariate, linear support vector machine analysis using leave-one-out cross-validation was then employed to discriminate girls with TS from typically developing controls based on differences in neuroanatomical spatial patterns and to assess how accurately such patterns translate across heterogeneous cohorts. VBM indicated that both TS cohorts had significantly reduced gray matter volume in the precentral, postcentral, and supramarginal gyri and enlargement of the left middle and superior temporal gyri. Support vector machine (SVM) classifiers achieved high accuracy for discriminating brain morphology patterns in TS from typically developing controls and also displayed spatial patterns consistent with the VBM results. Furthermore, the SVM classifiers identified additional neuroanatomical variations in individuals with TS, localized in the hippocampus, orbitofrontal cortex, insula, caudate, and cuneus. Our results demonstrate robust spatial patterns of altered brain morphology in developmentally dynamic populations with TS, providing further insight into the neuroanatomical correlates of cognitive-behavioral features in this condition.
View details for DOI 10.1016/j.neuroimage.2010.12.054
View details for Web of Science ID 000287556200001
View details for PubMedID 21195197
Posttraumatic stress disorder following traumatic injury: Narratives as unconscious indicators of psychopathology
BULLETIN OF THE MENNINGER CLINIC
2008; 72 (3): 179-190
Turner syndrome (TS) is a relatively common neurogenetic disorder characterized by complete or partial monosomy-X in a phenotypic female. TS is associated with a cognitive profile that typically includes intact intellectual function and verbal abilities with relative weaknesses in visual-spatial, executive, and social cognitive domains. In this report, we review previous and current research related to the cognitive profile of TS. We also discuss how cognitive impairments in this syndrome may reflect integrative rather than modular deficits. For example, the less commonly reported areas of verbal difficulty in TS and certain visual-spatial deficits seem significantly influenced by impairments in executive function and spatially loaded stimuli. We provide a summary of cognitive testing measures used in the assessment of visual-spatial and executive skills, which includes test domain descriptions as well as a comprehensive examination of social cognitive function in TS. This review concludes with a discussion of ecological interpretations regarding the meaning of cognitive deficits in TS at the individual level.
View details for DOI 10.1002/ddrr.79
View details for Web of Science ID 000273207500002
View details for PubMedID 20014362
EOSINOPHILIC MENINGOENCEPHALITIS: PSYCHIATRIC PRESENTATION AND TREATMENT
INTERNATIONAL JOURNAL OF PSYCHIATRY IN MEDICINE
2008; 38 (3): 287-295
Current conventional assessment methodologies used to diagnose posttraumatic stress disorder (PTSD) rely heavily on symptom counts obtained from clinical interviews or self-report questionnaires. Such measures may underestimate the impact of traumatic events, particularly in individuals who deny or repress emotional distress. This case report illustrates the use of two methods of narrative analysis to assess unconscious representations of PTSD. Linguistic analysis and a computerized analysis of referential activity were able to capture unconscious aspects of the traumatic experience.
View details for Web of Science ID 000260482800002
View details for PubMedID 18990054
Eosinophilic meningoencephalitis (EM) is usually a self-limited neurological illness commonly accompanied by a variety of neurological symptoms. The presence of acute psychotic symptoms in EM, however, has not previously been reported, and there is no literature to guide its treatment and management. In this case report, the onset of psychotic symptoms in a hypoactive delirium and their significant improvement following the administration of atypical antipsychotics are described in a boy with EM. This case report demonstrates the efficacy and safety of antipsychotic agents during the acute phase of meningoencephalitis.
View details for DOI 10.2190/PM.38.3.e
View details for Web of Science ID 000261315400005
View details for PubMedID 19069573