Doctor of Philosophy, University of Wisconsin Madison (2018)
Bachelor of Arts, Washington University (1998)
Despite evidence for effective integrated behavior therapy for treating comorbid obesity and depression, treatment response is highly variable and the underlying neurobiological mechanisms remain unknown. This hampers efforts to identify mechanistic targets in order to optimize treatment precision and potency. Funded within the NIH Science of Behavior Change (SOBC) Research Network, the 2-phased ENGAGE research project applies an experimental precision medicine approach to address this gap. The Phase 1 study focused on demonstrating technical feasibility, target engagement and potential neural mechanisms of responses to an integrated behavior therapy. This therapy combines a video-based behavioral weight loss program and problem-solving therapy for depression, with as-needed intensification of antidepressant medications, and its clinical effectiveness was demonstrated within a parent randomized clinical trial. Here, we describe the ENGAGE Phase 2 (ENGAGE-2) study protocol which builds on Phase 1 in 2 ways: (1) pilot testing of an motivational interviewing-enhanced, integrated behavior therapy in an independent, primarily minority patient sample, and (2) evaluation of a priori defined neural targets, specifically the negative affect (threat and sadness) circuits which demonstrated engagement and malleability in Phase 1, as mediators of therapeutic outcomes. Additionally, the Phase 2 study includes a conceptual and methodological extension to explore the role of microbiome-gut-brain and systemic immunological pathways in integrated behavioral treatment of obesity and depression. This protocol paper documents the conceptualization, design and the transdisciplinary methodologies in ENGAGE-2, which can inform future clinical and translational research in experimental precision medicine for behavior change and chronic disease management. Trial registration: ClinicalTrials.gov #NCT03841682.
View details for DOI 10.1016/j.cct.2020.106072
View details for PubMedID 32621905
View details for Web of Science ID 000509665600457
View details for Web of Science ID 000509665600825
Reduced hippocampal volume is frequently observed in posttraumatic stress disorder (PTSD), but the psychological processes associated with these alterations remain unclear. Given hippocampal involvement in memory and contextual representations of threat, we investigated relationships between retrospectively reported combat exposure, perceived threat, and hippocampal volume in trauma-exposed veterans. T1-weighted anatomical MRI scans were obtained from 56 veterans (4 women, 52 men; 39 with elevated PTSD symptoms, "PTSS" group) and hippocampal volume was estimated using automatic segmentation tools in FreeSurfer. Hippocampal volume was regressed on self-reported perceived threat from the Deployment Risk and Resilience Inventory, and combat exposure from the Combat Exposure Scale. As a secondary analysis, hippocampal volume was regressed on Clinician-Administered PTSD Scale (CAPS) symptoms. In veterans with elevated PTSD symptoms, hippocampal volume was inversely related to perceived threat while deployed while controlling for self-reported combat exposure. Hippocampal volume was also inversely correlated with avoidance/numbing CAPS symptoms. Future research should clarify the temporal milieu of these effects and investigate whether individual differences in hippocampal structure and function contribute to heightened threat appraisal at the time of trauma vs. subsequently elevated appraisals of traumatic events.
View details for DOI 10.1038/s41598-019-51533-x
View details for PubMedID 31624305
Previous studies have identified reduced heart rate variability (HRV) in post-traumatic stress disorder (PTSD), which may temporally precede the onset of the disorder. A separate line of functional neuroimaging research in PTSD has consistently demonstrated hypoactivation of the ventromedial prefrontal cortex (vmPFC), a key aspect of a descending neuromodulatory system that exerts inhibitory control over heart rate. No research to date, however, has simultaneously investigated whether altered vmPFC activation is associated with reduced HRV and elevated PTSD symptoms in the same individuals. Here, we collected fMRI data during alternating conditions of threat of shock and safety from shock in 51 male combat-exposed veterans with either high or low levels of PTSD symptoms. Pulse rate variability (PRV)-a HRV surrogate calculated from pulse oximetry-was assessed during a subsequent resting scan. Correlational analyses tested for hypothesized relationships between reduced vmPFC activation, lower PRV, and elevated PTSD symptomatology. We found that PTSD re-experiencing symptoms were inversely associated with high-frequency (HF)-PRV, thought to primarily reflect parasympathetic control of heart rate, in veterans with elevated PTSD symptoms. Reduced vmPFC activation for the contrast of safety-threat was associated both with lower HF-PRV and elevated PTSD re-experiencing symptoms. These results tie together previous observations of reduced HRV/PRV and impaired vmPFC function in PTSD and call for further research on reciprocal brain-body relationships in understanding PTSD pathophysiology.
View details for PubMedID 30793774
The current study attempted a rigorous test of the construct validity of a widely used self-report measure of dispositional mindfulness, the Five Facet Mindfulness Questionnaire (FFMQ), within the context of an active controlled randomized trial (n = 130). The trial included three arms: mindfulness-based stress reduction (MBSR), an active control condition that did not include instruction in mindfulness meditation (Health Enhancement Program [HEP]), and a waitlist control condition. Partial evidence for the convergent validity of the FFMQ was shown in correlations at baseline between FFMQ facets and measures of psychological symptoms and psychological well-being. In addition, facets of the FFMQ were shown to increase over the course of an MBSR intervention relative to a waitlist control condition. However, the FFMQ failed to show discriminant validity. Specifically, facets of the FFMQ were shown to increase over the course of the HEP intervention relative to the waitlist control condition. MBSR and HEP, in contrast, did not differ in changes in FFMQ score over time. Implications of these findings for the measurement and theory of mindfulness and MBSR are discussed. (PsycINFO Database Record
View details for PubMedID 26460893
View details for PubMedCentralID PMC4829487
Previous research in post-traumatic stress disorder (PTSD) has identified disrupted ventromedial prefrontal cortex (vmPFC) function in those with v. without PTSD. It is unclear whether this brain region is uniformly affected in all individuals with PTSD, or whether vmPFC dysfunction is related to individual differences in discrete features of this heterogeneous disorder.In a sample of 51 male veterans of Operation Enduring Freedom/Operation Iraqi Freedom, we collected functional magnetic resonance imaging data during a novel threat anticipation task with crossed factors of threat condition and temporal unpredictability. Voxelwise regression analyses related anticipatory brain activation to individual differences in overall PTSD symptom severity, as well as individual differences in discrete symptom subscales (re-experiencing, emotional numbing/avoidance, and hyperarousal).The vmPFC showed greater anticipatory responses for safety relative to threat, driven primarily by deactivation during threat anticipation. During unpredictable threat anticipation, increased PTSD symptoms were associated with relatively greater activation for threat v.However, simultaneous regression on individual symptom subscales demonstrated that this effect was driven specifically by individual differences in hyperarousal symptoms. Furthermore, this analysis revealed an additional, anatomically distinct region of the vmPFC in which re-experiencing symptoms were associated with greater activation during threat anticipation.Increased anticipatory responses to unpredictable threat in distinct vmPFC subregions were uniquely associated with elevated hyperarousal and re-experiencing symptoms in combat veterans. These results underscore the disruptive impact of uncertainty for veterans, and suggest that investigating individual differences in discrete aspects of PTSD may advance our understanding of underlying neurobiological mechanisms.
View details for DOI 10.1017/S0033291716000374
View details for Web of Science ID 000378716200008
View details for PubMedID 26979659
View details for PubMedCentralID PMC4900910
Respiration rate is known to correlate with aspects of psychological well-being, and attention to respiration is a central component of mindfulness meditation training. Both traditional contemplative systems and recent empirical evidence support an association between formal mindfulness practice and decreased respiration rate. However, the question of whether long-term mindfulness training is associated with stable, generalized changes in respiration has yet to be directly investigated. We analyzed respiration patterns across multiple time points, separated by two months or more, in a group of long-term mindfulness meditation practitioners (LTMs, n?=?31) and a matched group of non-meditators (Controls, n?=?38). On average, LTMs showed slower baseline respiration rate (RR) than Controls. Among LTMs, greater practice experience was associated with slower RR, independently of age and gender. Furthermore, this association was specific to intensive retreat practice, and was not seen for routine daily practice. Full days of meditation practice did not produce detectable changes in baseline RR, suggesting distal rather than immediate effects. All effects were independent of physiological characteristics including height, weight, body-mass index and waist-hip ratio. We discuss implications for continued study of the long-term effects of mindfulness training on health and well-being.
View details for PubMedID 27272738
Psychological processes such as expectancy, attention, and affect directly influence clinical outcomes. These factors are grouped together as "nonspecific" factors, or placebo effects, in the medical literature, and their individual contributions are rarely considered. The pain-reducing effects of analgesic treatments may reflect changes in these psychological factors, rather than pure drug effects on pain. Furthermore, drug effects may not be isolated by drug vs. placebo comparisons if drugs interact with relevant psychological processes.We sought to determine whether the analgesic effects of opioid and placebo treatment are mediated by changes in attention, expectancy, or affect.We crossed intravenous administration of a potent opioid analgesic, remifentanil, with information about drug delivery (treatment expectancy or placebo) using a balanced placebo design. We measured drug and treatment expectancy effects on pain, attention, and responses to emotional images. We also examined interactions with cue-based expectations about noxious stimulation or stimulus expectancy.Pain was additively influenced by treatment expectancy, stimulus expectancy, and drug concentration. Attention performance showed a small but significant interaction between drug and treatment expectancy. Finally, remifentanil enhanced responses to both positive and negative emotional images.The pain-relieving effects of opioid drugs are unlikely to be mediated by changes in threat or affective processing. Standard open-label opioid administration influences multiple clinically relevant cognitive and emotional processes. Psychological factors can combine with drug effects to influence multiple outcomes in distinct ways. The influence of specific psychological factors should be considered when developing and testing pharmacological treatments.
View details for DOI 10.1007/s00213-013-3296-1
View details for Web of Science ID 000331719100002
View details for PubMedID 24096537
View details for PubMedCentralID PMC3945427
Placebo treatments and opiate drugs are thought to have common effects on the opioid system and pain-related brain processes. This has created excitement about the potential for expectations to modulate drug effects themselves. If drug effects differ as a function of belief, this would challenge the assumptions underlying the standard clinical trial. We conducted two studies to directly examine the relationship between expectations and opioid analgesia. We administered the opioid agonist remifentanil to human subjects during experimental thermal pain and manipulated participants' knowledge of drug delivery using an open-hidden design. This allowed us to test drug effects, expectancy (knowledge) effects, and their interactions on pain reports and pain-related responses in the brain. Remifentanil and expectancy both reduced pain, but drug effects on pain reports and fMRI activity did not interact with expectancy. Regions associated with pain processing showed drug-induced modulation during both Open and Hidden conditions, with no differences in drug effects as a function of expectation. Instead, expectancy modulated activity in frontal cortex, with a separable time course from drug effects. These findings reveal that opiates and placebo treatments both influence clinically relevant outcomes and operate without mutual interference.
View details for DOI 10.1523/JNEUROSCI.0383-12.2012
View details for Web of Science ID 000305091800029
View details for PubMedID 22674280
View details for PubMedCentralID PMC3387557