16 results on '"Patrick Stetz"'
Search Results
2. Early changes in neural circuit function engaged by negative emotion and modified by behavioural intervention are associated with depression and problem-solving outcomes: A report from the ENGAGE randomized controlled trial
- Author
-
Andrea N Goldstein-Piekarski, Joseph Wielgosz, Lan Xiao, Patrick Stetz, Carlos G. Correa, Sarah E. Chang, Nan Lv, Lisa G. Rosas, Philip W. Lavori, Mark B. Snowden, Elizabeth M. Venditti, Janine M. Simmons, Joshua M. Smyth, Trisha Suppes, Megan A. Lewis, Olusola Ajilore, Jun Ma, and Leanne M. Williams
- Subjects
Depression ,Obesity ,Insula ,Amygdala ,Problem-solving ,Neuroimaging ,Medicine ,Medicine (General) ,R5-920 - Abstract
Background: Depression exerts a staggering toll that is worsened with co-occurring chronic conditions such as obesity. It is imperative to develop more effective interventions for depression and to identify objective and biological plausible neural mechanisms to understand intervention outcomes. The current study uses functional neuroimaging to determine whether a behavioural intervention changes the negative affect circuit and whether these changes relate to subsequent improvements in both symptom and problem-solving outcomes in depressed patients with co-occurring obesity. Methods: This study (‘ENGAGE’) was a pre-planned element of the randomized controlled trial, ‘RAINBOW’ (ClinicalTrials.gov NCT02246413). 108 depressed patients with obesity were randomized to receive an integrated collaborative care intervention (I-CARE) or usual care. Participants underwent functional neuroimaging using an established facial emotion task at baseline and two months (coinciding with the first two months of intervention focused on problem-solving therapy (‘PST’)). Amygdala, insula and anterior cingulate cortex activation was extracted using pre-planned definitions and standardized methods. The primary health and behavioural outcomes were depression symptom severity and problem-solving ability respectively, assessed at baseline, the main 6-month outcome point and at 12-month follow up. Mediation analyses used an intent-to-treat approach. Findings: PST, relative to usual care, reduced amygdala activation engaged by threat stimuli at two months. This reduction mediated subsequent improvements in depression severity in an intervention-dependent manner. PST did not change insula activation at two months but did temper the strength of the relationship between insula activation and improvements in problem-solving ability. Interpretation: The negative affect circuit may be an important neural target and potential mediator of PST in patients with comorbid obesity. Funding: US National Institutes of Health/National Heart Lung and Blood Institute R01 HL119453 and UH2/UH3 HL132368
- Published
- 2021
- Full Text
- View/download PDF
3. Problem-solving therapy–induced amygdala engagement mediates lifestyle behavior change in obesity with comorbid depression: a randomized proof-of-mechanism trial
- Author
-
Nan Lv, Philip W. Lavori, Trisha Suppes, Joshua M. Smyth, Elizabeth M. Venditti, Wesley K. Lefferts, Lan Xiao, Janine M. Simmons, Megan A. Lewis, Leanne M. Williams, Mark B Snowden, Lisa G. Rosas, Jun Ma, Andrea N. Goldstein-Piekarski, Joseph Wielgosz, Patrick Stetz, and Olusola Ajilore
- Subjects
Adult ,medicine.medical_specialty ,Medicine (miscellaneous) ,Amygdala ,Physical medicine and rehabilitation ,Neuroimaging ,Weight loss ,Functional neuroimaging ,Intervention (counseling) ,medicine ,Humans ,Obesity ,Life Style ,Depression (differential diagnoses) ,Nutrition and Dietetics ,Depression ,business.industry ,Mechanism (biology) ,medicine.disease ,Psychotherapy ,Original Research Communications ,medicine.anatomical_structure ,medicine.symptom ,business - Abstract
BACKGROUND: Depression hinders obesity treatment; elucidating mechanisms may enable treatment enhancements. OBJECTIVES: The aim was to investigate whether changes in neural targets in the negative affect circuit following psychotherapy mediate subsequent changes in weight and behaviors. METHODS: Adults (n = 108) with obesity and depression were randomly assigned to usual care or an intervention that delivered problem-solving therapy (PST) for depression over 2 mo. fMRI for brain imaging was performed at baseline and 2 mo. BMI, physical activity, and diet were measured at baseline and 12 mo. Mediation analysis assessed between-group differences in neural target changes using t test and correlations between neural target changes and outcome changes (simple and interaction effect) using ordinary least-squares regression. RESULTS: Compared with usual care, PST led to reductions in left amygdala activation (−0.75; 95% CI: −1.49, −0.01) and global scores of the negative affect circuit (−0.43; −0.81, −0.06), engaged by threat stimuli. Increases in amygdala activation and global circuit scores at 2 mo correlated with decreases in physical activity outcomes at 12 mo in the usual-care group; these relations were altered by PST. In relation to change in leisure-time physical activity, standardized β-coefficients were −0.67 in usual care and −0.01 in the intervention (between-group difference: 0.66; 0.02, 1.30) for change in left amygdala activation and −2.02 in usual care and −0.11 in the intervention (difference: 1.92; 0.64, 3.20) for change in global circuit scores. In relation to change in total energy expenditure, standardized β-coefficients were −0.65 in usual care and 0.08 in the intervention (difference: 0.73; 0.29, 1.16) for change in left amygdala activation and −1.65 in usual care and 0.08 in the intervention (difference: 1.74; 0.85, 2.63) for change in global circuit scores. Results were null for BMI and diet. CONCLUSIONS: Short-term changes in the negative affect circuit engaged by threat stimuli following PST for depression mediated longer-term changes in physical activity. This trial was registered at www.clinicaltrials.gov as NCT02246413 (https://clinicaltrials.gov/ct2/show/NCT02246413).
- Published
- 2021
- Full Text
- View/download PDF
4. Mediating Effects of Neural Targets on Depression, Weight, and Anxiety Outcomes of an Integrated Collaborative Care Intervention: The ENGAGE-2 Mechanistic Pilot Randomized Clinical Trial
- Author
-
Nan Lv, Olusola A. Ajilore, Lan Xiao, Elizabeth M. Venditti, Philip W. Lavori, Ben S. Gerber, Mark B. Snowden, Nancy E. Wittels, Corina R. Ronneberg, Patrick Stetz, Amruta Barve, Rohit Shrestha, Sushanth Dosala, Vikas Kumar, Tessa L. Eckley, Andrea N. Goldstein-Piekarski, Joshua M. Smyth, Lisa G. Rosas, Thomas Kannampallil, John Zulueta, Trisha Suppes, Leanne M. Williams, and Jun Ma
- Subjects
General Medicine - Published
- 2022
- Full Text
- View/download PDF
5. Accelerated neuromodulation therapy for Obsessive-Compulsive Disorder
- Author
-
Kelley P. Anderson, Elizabeth A. McCarthy, Brianna Wright, Booil Jo, Nolan R. Williams, Peter van Roessel, Sindu Menon, E. Cole, Leanne M. Williams, Maria Filippou-Frye, Keith D. Sudheimer, Carolyn I. Rodriguez, Anthony Lombardi, Lorrin M. Koran, Patrick Stetz, Thasveen Sandhu, Andrea N. Goldstein-Piekarski, and Andrea Varias
- Subjects
NCT03404609 ,Right frontal pole ,medicine.medical_specialty ,business.industry ,General Neuroscience ,05 social sciences ,Biophysics ,behavioral disciplines and activities ,Article ,050105 experimental psychology ,Neuromodulation (medicine) ,lcsh:RC321-571 ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,Obsessive compulsive ,Brain stimulation ,medicine ,0501 psychology and cognitive sciences ,Neurology (clinical) ,business ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,030217 neurology & neurosurgery - Abstract
Abbreviated Summary The open-label trial of Williams, Sudheimer, Cole, et al., suggests safety, feasibility, and high efficacy for treatment-refractory OCD of an accelerated, fMRI-guided, high-dose, cTBSmod protocol targeting the right frontal pole. Larger, randomized, controlled trials are needed to test the promising results of this pilot study. Clinicaltrials.gov Registry Numbers NCT03404609.
- Published
- 2021
- Full Text
- View/download PDF
6. Survivors of SARS-CoV-2 Infection Show Neuropsychiatric Sequelae Measured by Surveys, Neurocognitive Testing, and Magnetic Resonance Imaging: Preliminary Results
- Author
-
Philip M. Grant, Laura M. Hack, Hector Bonilla, Leanne M. Williams, Bin Jiang, Jerome A. Yesavage, Max Wintermark, Patrick Stetz, Aruna Subramanian, Jacob Brawer, Xue Zhang, and Megan Chesnut
- Subjects
Functional imaging ,Functional neuroimaging ,business.industry ,Cohort ,Medicine ,Brain Structure and Function ,Anxiety ,Cognition ,medicine.symptom ,business ,Neurocognitive ,Depression (differential diagnoses) ,Clinical psychology - Abstract
A significant number of individuals experience physical, cognitive, and mental health symptoms in the months after acute infection with SARS-CoV-2, the virus that causes COVID-19. This study assessed depressive and anxious symptoms, cognition, and brain structure and function in participants with symptomatic COVID-19 confirmed by PCR testing (n=100) approximately three months following infection, leveraging self-report questionnaires, objective neurocognitive testing, and structural and functional neuroimaging data. Preliminary results demonstrated that over 1/5 of our cohort endorsed clinically significant depressive and/or anxious symptoms, and >40% of participants had cognitive impairment on objective testing across multiple domains, consistent with ‘brain-fog’. While depression and one domain of quality of life (physical functioning) were significantly different between hospitalized and non-hospitalized participants, anxiety, cognitive impairment, and most domains of functioning were not, suggesting that the severity of SARS-CoV-2 infection does not necessarily relate to the severity of neuropsychiatric outcomes and impaired functioning in the months after infection. Furthermore, we found that the majority of participants in a subset of our cohort who completed structural and functional neuroimaging (n=15) had smaller olfactory bulbs and sulci in conjunction with anosmia. We also showed that this subset of participants had dysfunction in attention network functional connectivity and ventromedial prefrontal cortex seed-based functional connectivity. These functional imaging dysfunctions have been observed previously in depression and correlated with levels of inflammation. Our results support and extend previous findings in the literature concerning the neuropsychiatric sequelae associated with long COVID. Ongoing data collection and analyses within this cohort will allow for a more comprehensive understanding of the longitudinal relationships between neuropsychiatric symptoms, neurocognitive performance, brain structure and function, and inflammatory and immune profiles.
- Published
- 2021
- Full Text
- View/download PDF
7. Mediating Effects of Neural Targets on Depression, Weight and Anxiety Outcomes of an Integrated Collaborative Care Intervention: The ENGAGE-2 Mechanistic Pilot RCT
- Author
-
Thomas George Kannampallil, Nancy E. Wittels, Jun Ma, Amruta Barve, Elizabeth M. Venditti, Nan Lv, Corina R. Ronneberg, Andrea Goldstein-Piekarski, John Zulueta, Trisha Suppes, Tessa L. Eckley, Mark Snowden, Rohit Shrestha, Patrick Stetz, Philip W. Lavori, Vikas Kumar, Olusola Ajilore, Leanne M. Williams, Sushanth Dosala, Lisa G. Rosas, Joshua M. Smyth, Lan Xiao, and Ben S. Gerber
- Subjects
medicine.medical_specialty ,business.industry ,Collaborative Care ,Cognition ,law.invention ,Clinical trial ,Randomized controlled trial ,law ,Intervention (counseling) ,Physical therapy ,Medicine ,Anxiety ,medicine.symptom ,business ,Body mass index ,Depression (differential diagnoses) - Abstract
Background: Integrated treatments for depression (and associated anxiety) and obesity are lacking; mechanisms are poorly investigated. This mechanistic pilot trial tested the degree to which engaging pre-specified neural targets at 2 months produces desired outcomes at 6 months. Methods: Adults with a body mass index (BMI) of ≥30 (≥27, if Asian) and Patient Health Questionnaire-9 (PHQ-9) score of ≥10 were recruited from academic internal medicine clinics between March 1, 2019 and March 19, 2020, and followed for 6 months until August 31, 2020. Participants were randomized to receive usual care (n=35) or an integrated collaborative care intervention (n=71), providing 6 problem-solving therapy (PST) sessions for depression by 2 months, 3 additional PST sessions and 11 home videos on lifestyle changes for weight loss by 6 months. Outcomes were changes in BMI, Depression Symptom Checklist 20-item (SCL-20) scores, and Generalized Anxiety Disorder Scale (GAD-7) scores at 6 months. Neural targets were changes in affective, cognitive control, and default mode circuits by functional neuroimaging at 2 months. Outcomes: Among 106 participants (mean [SD] age 47.0 [11.9] years, 76% women, 55% Blacks, 20% Latino, BMI 37.1 [6.0], SCL-20 1.2 [0.7], GAD-7 6.9 [4.8]), 86.8% completed the trial. The intervention led to significant reductions in SCL-20 (-0.3 [95% CI: -0.6, -0.1]) and GAD-7 (-2.9 [-4.7, -1.1]), but not BMI, at 6 months compared with usual care. Changes in the activation or functional connectivity of neural targets in the negative affect (anterior insula, subgenual and pregenual ACC, amygdala) and cognitive control circuits (dlPFC, dACC) at 2 months significantly correlated with changes in GAD-7, but not SCL-20 or BMI, at 6 months, and the correlations differed by the intervention vs. usual care. Effect sizes were medium to large (0.41ꟷ1.18 SDs). Changes in the neural targets of the cognitive control circuit, but not the negative affect circuit, at 2 months differed by treatment group. Effect sizes were medium (0.58ꟷ0.79 SDs). Interpretation: Short-term changes in the cognitive control circuit mediated changes in anxiety symptoms, suggesting possible neural mechanisms to target for enhanced treatment effect. Clinical Trial Registration Details: ClinicalTrials.gov Identifier: NCT03841682. Funding Information: National Heart, Lung, and Blood Institute grant number UH2HL132368 and UH3HL132368. Declaration of Interests: Dr. Jun Ma is a paid scientific consultant for Health Mentor, Inc. (San Jose, CA). Dr. Leanne M. Williams is on the Scientific Advisory Board for One Mind Psyberguide and the External Advisory Board for the Laureate Institute for Brain Research. Dr. Olusola A. Ajilore is the co-founder of Keywise AI and serves on the advisory boards of Blueprint Health and Embodied Labs. The other authors report no conflicts of interest. Dr. Thomas Kannampallil is a paid consultant for Pfizer, Inc, outside of this work Ethics Approval Statement: The Institutional Review Boards for the University of Illinois at Chicago and Stanford University approved the study. All participants provided written consent.
- Published
- 2021
- Full Text
- View/download PDF
8. Early changes in neural circuit function engaged by negative emotion and modified by behavioural intervention are associated with depression and problem-solving outcomes: A report from the ENGAGE randomized controlled trial
- Author
-
Olusola Ajilore, Joseph Wielgosz, Patrick Stetz, Philip W. Lavori, Joshua M. Smyth, Leanne M. Williams, Lan Xiao, Jun Ma, Nan Lv, Janine M. Simmons, Andrea N. Goldstein-Piekarski, Trisha Suppes, Megan A. Lewis, Elizabeth M. Venditti, Lisa G. Rosas, Mark B Snowden, Carlos Alexander Grajales Correa, and Sarah E. Chang
- Subjects
0301 basic medicine ,Adult ,Male ,Medicine (General) ,Mediation (statistics) ,medicine.medical_specialty ,Emotions ,Problem-solving ,Collaborative Care ,Insula ,Neuroimaging ,General Biochemistry, Genetics and Molecular Biology ,law.invention ,03 medical and health sciences ,R5-920 ,0302 clinical medicine ,Physical medicine and rehabilitation ,Randomized controlled trial ,Functional neuroimaging ,law ,Behavior Therapy ,Intervention (counseling) ,Connectome ,Medicine ,Humans ,Obesity ,Anterior cingulate cortex ,Depression (differential diagnoses) ,Problem Solving ,Aged ,Cerebral Cortex ,business.industry ,Depression ,General Medicine ,Middle Aged ,Amygdala ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,business ,Research Paper - Abstract
Background Depression exerts a staggering toll that is worsened with co-occurring chronic conditions such as obesity. It is imperative to develop more effective interventions for depression and to identify objective and biological plausible neural mechanisms to understand intervention outcomes. The current study uses functional neuroimaging to determine whether a behavioural intervention changes the negative affect circuit and whether these changes relate to subsequent improvements in both symptom and problem-solving outcomes in depressed patients with co-occurring obesity. Methods This study (‘ENGAGE’) was a pre-planned element of the randomized controlled trial, ‘RAINBOW’ (ClinicalTrials.gov NCT02246413). 108 depressed patients with obesity were randomized to receive an integrated collaborative care intervention (I-CARE) or usual care. Participants underwent functional neuroimaging using an established facial emotion task at baseline and two months (coinciding with the first two months of intervention focused on problem-solving therapy (‘PST’)). Amygdala, insula and anterior cingulate cortex activation was extracted using pre-planned definitions and standardized methods. The primary health and behavioural outcomes were depression symptom severity and problem-solving ability respectively, assessed at baseline, the main 6-month outcome point and at 12-month follow up. Mediation analyses used an intent-to-treat approach. Findings PST, relative to usual care, reduced amygdala activation engaged by threat stimuli at two months. This reduction mediated subsequent improvements in depression severity in an intervention-dependent manner. PST did not change insula activation at two months but did temper the strength of the relationship between insula activation and improvements in problem-solving ability. Interpretation The negative affect circuit may be an important neural target and potential mediator of PST in patients with comorbid obesity. Funding US National Institutes of Health/National Heart Lung and Blood Institute R01 HL119453 and UH2/UH3 HL132368
- Published
- 2020
9. Mapping Neural Circuit Biotypes to Symptoms and Behavioral Dimensions of Depression and Anxiety
- Author
-
Patrick Stetz, Jun Ma, Scott L. Fleming, Leanne M. Williams, Bailey Holt-Gosselin, Tali M. Ball, Katherine A. Grisanzio, Brooke R. Staveland, Zoe Samara, Arielle S. Keller, and Andrea N. Goldstein-Piekarski
- Subjects
Psychiatry ,Salience (language) ,Depression ,Emotional functions ,Cognition ,Anxiety ,Institutional review board ,Anxiety Disorders ,Mood ,Informed consent ,medicine ,Humans ,Generalizability theory ,medicine.symptom ,Psychology ,Biological Psychiatry ,Default mode network ,Depression (differential diagnoses) ,Clinical psychology - Abstract
Background: Despite tremendous advances in characterizing human brain circuits that govern emotional and cognitive functions that are impaired in depression and anxiety, we lack a circuitbased taxonomy that captures transdiagnostic heterogeneity and informs clinical decision making. Methods: We develop and test a novel system for quantifying six brain circuits reproducibly and at the individual patient level. We implement standardized circuit definitions relative to a healthy reference group, and algorithms to generate circuit function and dysfunction scores for the overall circuit and its constituent regions. Outcomes: In primary and generalizability samples of depression and anxiety (n=251) we demonstrate that overall disconnections within task-free salience and default mode circuits map onto symptoms of anxious avoidance, loss of pleasure, threat dysregulation, and negative emotional biases – core characteristics that transcend diagnoses – and poorer daily function. Regional dysfunctions within task-evoked cognitive control and affective circuits implicate more specific cognitive symptoms and valence-congruent behavioral disruptions. Circuit dysfunction scores also predict response to pharmacological and behavioral therapies in an independent sample (n=207). Interpretation: Our findings articulate circuit dimensions that parse the heterogeneity of depression and anxiety and have direct clinical translational significance. Our novel system offers a foundation for deploying standardized circuit assessments across research groups, trials and clinics to advance more precise classifications and treatment targets for psychiatry. Funding: This work was supported by the National Institutes of Health [grant numbers R01MH101496 (LMW), UH2HL132368 (JM, LMW), F32MH108299 (ANG-P), T32MH019938 (TMB), and K23MH113708 (TMB)]. Declaration of Interests: LMW declares US Pants. App. 10/034,645 and 15/820,338: Systems and methods for detecting complex networks in MRI image data. ANG-P, TMB, ZS, KAG, SLF, ASK, BRS, and BHG declare no competing interests. Ethics Approval Statement: All procedures were approved by the Stanford University Institutional Review Board (IRB 27937 and 41837) or Western Sydney Area Health Service Human Research Ethics Committee. All participants provided written informed consent prior to study procedures.
- Published
- 2020
10. Identifying response and predictive biomarkers for Transcranial magnetic stimulation outcomes: protocol and rationale for a mechanistic study of functional neuroimaging and behavioral biomarkers in veterans with Pharmacoresistant depression
- Author
-
Mark S. George, Kelvin O. Lim, Nicole C. Walker, Paul E. Holtzheimer, Noah S. Philip, John T. Coman, Leanne M. Williams, F. Andrew Kozel, Jong H. Yoon, Laura M. Hack, Michelle Madore, and Patrick Stetz
- Subjects
050103 clinical psychology ,medicine.medical_specialty ,lcsh:RC435-571 ,medicine.medical_treatment ,Prefrontal Cortex ,Neuroimaging ,Cognitive control network ,Default mode network (DMN) ,03 medical and health sciences ,Study Protocol ,0302 clinical medicine ,Quality of life (healthcare) ,Physical medicine and rehabilitation ,Functional neuroimaging ,lcsh:Psychiatry ,Medicine ,Humans ,0501 psychology and cognitive sciences ,Default mode network ,Veterans ,Major depressive disorder (MDD) ,Depressive Disorder, Major ,Dorsolateral prefrontal cortex (DLPFC) ,medicine.diagnostic_test ,business.industry ,Depression ,Functional Neuroimaging ,05 social sciences ,Repetitive Transcranial magnetic stimulation (TMS) ,Cognition ,Biomarker ,medicine.disease ,Magnetic Resonance Imaging ,Transcranial Magnetic Stimulation ,Transcranial magnetic stimulation ,Functional magnetic resonance imaging (fMRI) ,Psychiatry and Mental health ,Treatment resistant depression (TRD) ,Quality of Life ,Major depressive disorder ,business ,Functional magnetic resonance imaging ,030217 neurology & neurosurgery ,Biomarkers - Abstract
Background Although repetitive transcranial magnetic stimulation (‘TMS’) is becoming a gold standard treatment for pharmacoresistant depression, we lack neural target biomarkers for identifying who is most likely to respond to TMS and why. To address this gap in knowledge we evaluate neural targets defined by activation and functional connectivity of the dorsolateral prefrontal cortex-anchored cognitive control circuit, regions of the default mode network and attention circuit, and interactions with the subgenual anterior cingulate. We evaluate whether these targets and interactions between them change in a dose-dependent manner, whether changes in these neural targets correspond to changes in cognitive behavioral performance, and whether baseline and early change in neural target and cognitive behavioral performance predict subsequent symptom severity, suicidality, and quality of life outcomes. This study is designed as a pragmatic, mechanistic trial partnering with the National Clinical TMS Program of the Veteran’s Health Administration. Methods Target enrollment consists of 100 veterans with pharmacoresistant Major Depressive Disorder (MDD). All veterans will receive a clinical course of TMS and will be assessed at ‘baseline’ pre-TMS commencement, ‘first week’ after initiation of TMS (targeting five sessions) and ‘post-treatment’ at the completion of TMS (targeting 30 sessions). Veterans will be assessed using functional magnetic resonance imaging (fMRI), a cognitive behavioral performance battery, and established questionnaires. Multivariate linear mixed models will be used to assess whether neural targets change with TMS as a function of dose (Aim 1), whether extent and change of neural target relates to and predicts extent of behavioral performance (Aim 3), and whether extent of neural target change predicts improvement in symptom severity, suicidality, and quality of life (Aim 3). For all three aims, we will also assess the contribution of baseline moderators such as biological sex and age. Discussion To our knowledge, our study will be the first pragmatic, mechanistic observational trial to use fMRI imaging and cognitive-behavioral performance as biomarkers of TMS treatment response in pharmacoresistant MDD. The results of this trial will allow providers to select suitable candidates for TMS treatment and better predict treatment response by assessing circuit connectivity and cognitive-behavioral performance at baseline and during early treatment. Trial registration ClinicalTrials.gov NCT04663481, December 5th, 2020, retrospectively registered. The first veteran was enrolled October 30th, 2020.
- Published
- 2020
11. Problem Solving Therapy-induced Amygdala Engagement Mediates Weight Loss and Lifestyle Behavior Change in Patients With Obesity and Depression: A Randomized Controlled Trial
- Author
-
Andrea N. Goldstein-Piekarski, Leanne M. Williams, Trisha Suppes, Mark Snowden, Wesley K. Lefferts, Lan Xiao, Megan A. Lewis, Joshua M. Smyth, Nan Lv, Joseph Wielgosz, Lisa G. Rosas, Elizabeth M. Venditti, Jun Ma, Patrick Stetz, Olusola Ajilore, Philip W. Lavori, and Janine M. Simmons
- Subjects
medicine.medical_specialty ,business.industry ,medicine.disease ,Obesity ,Amygdala ,law.invention ,Problem solving therapy ,medicine.anatomical_structure ,Randomized controlled trial ,Weight loss ,law ,medicine ,Physical therapy ,In patient ,medicine.symptom ,business ,Depression (differential diagnoses) ,Lifestyle behavior - Abstract
Background: Behavioral interventions for obesity have modest and variable effectiveness. Emotion dysregulation may hinder effective weight loss interventions, especially among those with comorbid depression. Whether neural mechanisms related to emotion dysregulation mediate the effect of behavioral intervention on improving health behaviors in obesity combined with depression is unknown. Hyperactivation of the amygdala and loss of functional connectivity with the anterior cingulate regions are neural characteristics of unhealthy responses to negative emotion and accompanying emotion dysregulation. Methods: Using data from a randomized clinical trial of 108 primary care adult patients with obesity and depression, we investigated whether changes in amygdala activity and connectivity following problem solving therapy for depression over 2 months mediate weight loss, physical activity, and/or dietary outcomes at 6 and 12 months. Results: Compared with controls (n=49), intervention participants (n=59) had a significant blunting of the otherwise unhealthy increase in activity of the bilateral amygdala at 2 months (right: -0.83, 95% CI -1.55 to -0.11; left: -0.86, -1.63 to -0.10). While increases in amygdala activity significantly correlated with decreases in leisure-time physical activity levels and total energy expenditure at 12 months in the control group, this relationship was tempered or reversed among intervention participants (for physical activity, right: usual care -692.9, -1365.3 to -20.6; interaction 652.2, -115.4 to 1419.9; left: usual care -686.0, -1127.9 to -244.1; interaction 664.7, 73.1 to 1256.4; for energy expenditure, right: usual care -1.82, -3.08 to -0.56; interaction 1.94, 0.50 to 3.38; left: usual care -1.72, -2.51 to -0.93; interaction 1.89, 0.84 to 2.94). Compared with controls, intervention participants had a significant increase of the otherwise unhealthy loss of amygdala-subgenual anterior cingulate connectivity at 2 months (0.78, 0.05 to 1.52). This increase in functional connectivity significantly correlated with a decrease in BMI at 6 months among intervention participants (usual care 0.04, -0.42 to 0.50; interaction -0.61, -1.20 to -0.02) and an increase in fruit and vegetable intake at 12 months across all participants (usual care 1.42, 0.27 to 2.57; interaction -0.95, -2.36 to 0.46). Conclusions: These findings highlight potential neural mechanism for optimizing the efficacy of behavioral intervention in comorbid obesity and depression.Trial registration: ClinicalTrials.gov#NCT02246413.URL: https://clinicaltrials.gov/ct2/show/NCT02246413.
- Published
- 2020
- Full Text
- View/download PDF
12. The ENGAGE-2 study: Engaging self-regulation targets to understand the mechanisms of behavior change and improve mood and weight outcomes in a randomized controlled trial (Phase 2)
- Author
-
Amruta Barve, Joseph Wielgosz, Janine M. Simmons, Philip W. Lavori, Patrick Stetz, Nan Lv, Aashutos S. Patel, Elizabeth M. Venditti, Joshua M. Smyth, Jun Ma, Mark Snowden, Leanne M. Williams, Ben S. Gerber, Corina R. Ronneberg, Lisa G. Rosas, Nancy E. Wittels, Tessa L. Eckley, Andrea N. Goldstein-Piekarski, Olusola Ajilore, and Lan Xiao
- Subjects
Protocol (science) ,Psychotherapist ,Conceptualization ,business.industry ,media_common.quotation_subject ,Behavior change ,Translational research ,General Medicine ,Precision medicine ,Article ,Antidepressive Agents ,law.invention ,Self-Control ,Sadness ,Affect ,Mood ,Randomized controlled trial ,law ,Behavior Therapy ,Medicine ,Humans ,Pharmacology (medical) ,Obesity ,business ,media_common - Abstract
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 #NCT 03,841,682.
- Published
- 2020
13. Abstract P223: Reduced Nonconscious Reactivity to Threat in Amygdala Mediates Physical Activity and Energy Expenditure in Integrated Behavior Therapy for Adults With Obesity and Comorbid Depression
- Author
-
Philip W. Lavori, Leanne M. Williams, Nan Lv, Megan A. Lewis, Patrick Stetz, Wesley K. Lefferts, Mark Snowden, Olusola Ajilore, Lisa G. Rosas, Lan Xiao, Elizabeth M. Venditti, Jun Ma, Joshua M. Smyth, Andrea N. Goldstein-Piekarski, Joseph Wielgosz, and Patricia Suppes
- Subjects
business.industry ,Physical activity ,medicine.disease ,Amygdala ,Obesity ,medicine.anatomical_structure ,Energy expenditure ,Physiology (medical) ,medicine ,Biological neural network ,In patient ,Cardiology and Cardiovascular Medicine ,business ,Reactivity (psychology) ,Depression (differential diagnoses) ,Clinical psychology - Abstract
Introduction: Neural mechanisms underlying behavior therapy in obesity are poorly understood, particularly in patients with comorbid depression. Putative targets include neural circuits for conscious and nonconscious emotion regulation. Hypothesis: Changes in a priori neural circuits for emotion regulation from baseline (0) to 2 mo (mediators, M) mediate changes in BMI, physical activity, and eating behaviors from 0 to 6 or 12 mo (outcomes, Y). Methods: In a trial of integrated behavior therapy, adults with obesity and depression were randomized to intervention (n=59) or usual care (n=49). The yearlong intervention included 6 in-person problem solving therapy (PST) sessions for depression by 2 mo, 3 additional PST sessions for depression and 11 home videos on lifestyle changes for weight loss by 6 mo, and 6 maintenance calls by 12 mo. Participants completed validated conscious and nonconscious facial emotion viewing tasks in fMRI at 0 and 2 mo (time point corresponding to initial PST for depression in the intervention) and weight and height (baseline only) measurements, 7-day physical activity recalls, and 24-hour dietary recalls at 0, 6, and 12 mo. Analyses tested mediation as showing both a significant treatment effect (X) of the intervention vs. usual care on the mediator (X->M, path a ) and a significant correlation of the mediator with the outcome either as a main effect or an interaction effect by treatment group (M->Y, path b ). Results: Compared with usual care, the intervention led to significantly reduced nonconscious reactivity to threat-related facial emotions (fear, anger) at 2 mo for the left (-0.89, 95% CI -1.64 to -0.14; P =.02) and right amygdala (-0.84, 95% CI -1.54 to -0.13; P =.02) ( path a ). These reductions correlated significantly with increased leisure-time physical activity (MET minutes/wk) at 12 mo: main effect -686.0 (95% CI -1127.9 to -244.1; P =.003) and interaction effect 664.7 (95% CI 73.1 to 1256.4; P =.03) for the left amygdala and main effect -692.9 (95% CI -1365.3 to -20.6; P= .04) for the right amygdala. Similarly, the reductions correlated significantly with increased energy expenditure (kcal/kg/d) at 12 mo: main effect -1.72 (95% CI -2.49 to -0.95; P P P =.006) and interaction effect 1.94 (95% CI 0.50 to 3.38; P =.01) for the right amygdala ( path b ). Nonconscious reactivity to threat in bilateral amygdala did not correlate significantly with changes in BMI or eating behaviors. Conclusions: Reduced nonconscious reactivity to threat in bilateral amygdala in response to initial PST for depression significantly mediated improvements in leisure-time physical activity and energy expenditure. Results advance the understanding of neural mechanisms underlying behavior therapy in obesity and inform intervention optimization to enhance efficacy.
- Published
- 2020
- Full Text
- View/download PDF
14. Early Change in Neural Circuit Function Engaged by Negative Emotion Mediates Later Depression and Problem-Solving Outcomes Following Behavioural Intervention
- Author
-
Patrick Stetz, Trisha Suppes, Leanne M. Williams, Philip W. Lavori, Andrea Goldstein-Piekarski, Joseph Wielgosz, Janine Simmons, Nan Lv, Sarah Chang, Jun Ma, Mark Snowden, Megan A. Lewis, Elizabeth M. Venditti, Lan Xiao, Lisa G. Rosas, Carlos Alexander Grajales Correa, and Joshua M. Smyth
- Subjects
Mediation (statistics) ,medicine.anatomical_structure ,Neuroimaging ,Functional neuroimaging ,Intervention (counseling) ,medicine ,Collaborative Care ,Psychology ,Insula ,Anterior cingulate cortex ,Depression (differential diagnoses) ,Clinical psychology - Abstract
Background: There is a need to understand the neural mechanisms targeted by behavioural therapy for depression and how these mechanisms relate to clinical outcomes. We used functional neuroimaging to assess the neural mechanisms that are modified by behavioural therapy and mediate subsequent clinical outcomes in depression. Methods: Participants with depression, co-occurring with obesity, from a parent RAINBOW trial, were randomised to an integrated collaborative care intervention (I-CARE) (n=59) or usual care (n=49). Functional neuroimaging was undertaken at baseline and at 2 months, coinciding with initial 2-months of I-CARE that implemented a 7-step problem-solving therapy process and behavioural activation (for brevity, “PST”). Neural targets were the amygdala, insula, and anterior cingulate cortex (ACC) regions of the negative affect circuit engaged by established tasks presenting threat-related and sad stimuli. Regression models evaluated if early change in neural function mediated the effect of PST on depression severity and problem-solving outcomes at 6- and 12-months post-randomization. Findings: Compared with usual care, PST led to a reduction at 2 months in amygdala activation (Right: b=-0.83, 95% CI -1.55 to -0.11; Left: b=-0.86, -1.63 to -0.10) and amygdala-ACC connectivity (b=0.78, 0.05 to 1.52) engaged by threat stimuli. This PST-dependent reduction in amygdala activation mediated improvement of depression at 6 months relative to usual care. PST also tempered the relationship between insula activation and improved problem solving at 6 and 12 months. Interpretation: PST modifies neural targets within the negative affect circuit to improve symptoms and problem-solving relevant to the clinical and functional recovery of depression. Funding Statement: US National Institutes of Health/National Heart Lung and Blood Institute R01 HL119453 and UH2/UH3 HL132368. Declaration of Interests: LMW is on the Scientific Advisory Board for One Mind Psyberguide and the External Advisory Board for the Laureate Institute for Brain Research. JM is a paid scientific consultant for Health Mentor, Inc. (San Jose, CA). OA is the co-founder of Keywise AI and the servers on the advisory boards of Blueprint Health and Embodied Labs. All other authors do not have anything to declare. Ethics Approval Statement: The Institutional Review Boards for the Stanford University and the University of Illinois at Chicago approved the study.
- Published
- 2020
- Full Text
- View/download PDF
15. Altered Anterior Insula Function Precedes Improved Problem Solving in a Mechanistic Treatment Trial for Depression
- Author
-
Nan Lv, Philip W. Lavori, Leanne M. Williams, Tricia Suppes, Andrea N. Goldstein-Piekarski, Patrick Stetz, Joseph Wielgosz, Jun Ma, and Lan Xiao
- Subjects
Anterior insula ,Treatment trial ,business.industry ,Medicine ,business ,Neuroscience ,Biological Psychiatry ,Depression (differential diagnoses) - Published
- 2020
- Full Text
- View/download PDF
16. Activation of Cognitive Control Network During Inhibition Processing Dynamically Predicts Symptom Outcomes for Depression: A 24-month Longitudinal Study
- Author
-
Nan Lv, Philip W. Lavori, Janine M. Simmons, Leanne M. Williams, Xue Zhang, Patrick Stetz, Lan Xiao, Lisa G. Rosas, Elizabeth M. Venditti, Mark Snowden, Jun Ma, Joshua M. Smyth, Olusola Ajilore, Trisha Suppes, Andrea N. Goldstein-Piekarski, and Megan A. Lewis
- Subjects
Longitudinal study ,medicine.medical_specialty ,Physical medicine and rehabilitation ,business.industry ,medicine ,Cognitive control network ,business ,Biological Psychiatry ,Depression (differential diagnoses) - Published
- 2021
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.