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Mediating Effects of Neural Targets on Depression, Weight and Anxiety Outcomes of an Integrated Collaborative Care Intervention: The ENGAGE-2 Mechanistic Pilot RCT

26 Pages Posted: 15 Jul 2021

See all articles by Jun Ma

Jun Ma

University of Illinois at Chicago - Department of Medicine

Nan Lv

University of Illinois at Chicago - Institute for Health Research and Policy

Olusola A. Ajilore

University of Illinois at Chicago - Department of Psychiatry

Lan Xiao

Stanford University - Department of Epidemiology and Population Health

Elizabeth Venditti

University of Pittsburgh - Department of Psychiatry

Philip Lavori

Stanford University - Department of Psychiatry and Behavioral Sciences

Ben S. Gerber

University of Massachusetts - Department of Population and Quantitative Health Sciences

Mark Snowden

University of Washington - Department of Psychiatry and Behavioral Sciences

Nancy E. Wittels

University of Illinois at Chicago - Department of Medicine

Corina R. Ronneberg

University of Illinois at Chicago - Department of Medicine

Patrick Stetz

Stanford University - Department of Psychiatry and Behavioral Sciences

Amruta Barve

University of Illinois at Chicago - Institute for Health Research and Policy

Rohit Shrestha

University of Illinois at Chicago - Institute for Health Research and Policy

Sushanth Dosala

University of Illinois at Chicago - Institute for Health Research and Policy

Vikas Kumar

University of Illinois at Chicago - Department of Medicine

Tessa L. Eckley

University of Illinois at Chicago - Institute for Health Research and Policy

Andrea Goldstein-Piekarski

Stanford University - Department of Psychiatry and Behavioral Sciences; Government of the United States of America - Sierra Pacific MIRECC

Joshua Smyth

Pennsylvania State University - Departments of Biobehavioral Health and Medicine

Lisa G. Rosas

Stanford University - Department of Psychiatry and Behavioral Sciences

Thomas Kannampallil

University of Illinois at Chicago - Institute for Health Research and Policy

John Zulueta

University of Illinois at Chicago - Department of Psychiatry

Trisha Suppes

Stanford University - Department of Psychiatry and Behavioral Sciences

Leanne M. Williams

Stanford University - Department of Psychiatry and Behavioral Sciences; Government of the United States of America - Sierra Pacific MIRECC

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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.

Keywords: negative affect; cognitive control; functional neuroimaging; obesity; depression; anxiety

Suggested Citation

Ma, Jun and Lv, Nan and Ajilore, Olusola A. and Xiao, Lan and Venditti, Elizabeth and Lavori, Philip and Gerber, Ben S. and Snowden, Mark and Wittels, Nancy E. and Ronneberg, Corina R. and Stetz, Patrick and Barve, Amruta and Shrestha, Rohit and Dosala, Sushanth and Kumar, Vikas and Eckley, Tessa L. and Goldstein-Piekarski, Andrea and Smyth, Joshua and Rosas, Lisa G. and Kannampallil, Thomas and Zulueta, John and Suppes, Trisha and Williams, Leanne M., Mediating Effects of Neural Targets on Depression, Weight and Anxiety Outcomes of an Integrated Collaborative Care Intervention: The ENGAGE-2 Mechanistic Pilot RCT. Available at SSRN: https://ssrn.com/abstract=3887444 or http://dx.doi.org/10.2139/ssrn.3887444

Jun Ma (Contact Author)

University of Illinois at Chicago - Department of Medicine ( email )

Chicago, IL
United States

Nan Lv

University of Illinois at Chicago - Institute for Health Research and Policy

1200 W Harrison St
Chicago, IL 60607
United States

Olusola A. Ajilore

University of Illinois at Chicago - Department of Psychiatry

1200 W Harrison St
Chicago, IL 60607
United States

Lan Xiao

Stanford University - Department of Epidemiology and Population Health

Stanford, CA 94305
United States

Elizabeth Venditti

University of Pittsburgh - Department of Psychiatry

135 N Bellefield Ave
Pittsburgh, PA 15260
United States

Philip Lavori

Stanford University - Department of Psychiatry and Behavioral Sciences

401 Quarry Road
Stanford, CA 94304-5718
United States

Ben S. Gerber

University of Massachusetts - Department of Population and Quantitative Health Sciences

MA
United States

Mark Snowden

University of Washington - Department of Psychiatry and Behavioral Sciences

Seattle, WA 98195
United States

Nancy E. Wittels

University of Illinois at Chicago - Department of Medicine

1200 W Harrison St
Chicago, IL 60607
United States

Corina R. Ronneberg

University of Illinois at Chicago - Department of Medicine

1200 W Harrison St
Chicago, IL 60607
United States

Patrick Stetz

Stanford University - Department of Psychiatry and Behavioral Sciences

401 Quarry Road
Stanford, CA 94304-5718
United States

Amruta Barve

University of Illinois at Chicago - Institute for Health Research and Policy

1200 W Harrison St
Chicago, IL 60607
United States

Rohit Shrestha

University of Illinois at Chicago - Institute for Health Research and Policy

1200 W Harrison St
Chicago, IL 60607
United States

Sushanth Dosala

University of Illinois at Chicago - Institute for Health Research and Policy

1200 W Harrison St
Chicago, IL 60607
United States

Vikas Kumar

University of Illinois at Chicago - Department of Medicine

1200 W Harrison St
Chicago, IL 60607
United States

Tessa L. Eckley

University of Illinois at Chicago - Institute for Health Research and Policy

1200 W Harrison St
Chicago, IL 60607
United States

Andrea Goldstein-Piekarski

Stanford University - Department of Psychiatry and Behavioral Sciences ( email )

401 Quarry Road
Stanford, CA 94304-5718
United States

Government of the United States of America - Sierra Pacific MIRECC ( email )

3801 Miranda Ave
Palo Alto, CA 94304
United States

Joshua Smyth

Pennsylvania State University - Departments of Biobehavioral Health and Medicine

University Park
State College, PA 16802
United States

Lisa G. Rosas

Stanford University - Department of Psychiatry and Behavioral Sciences

401 Quarry Road
Stanford, CA 94304-5718
United States

Thomas Kannampallil

University of Illinois at Chicago - Institute for Health Research and Policy

1200 W Harrison St
Chicago, IL 60607
United States

John Zulueta

University of Illinois at Chicago - Department of Psychiatry

1200 W Harrison St
Chicago, IL 60607
United States

Trisha Suppes

Stanford University - Department of Psychiatry and Behavioral Sciences

401 Quarry Road
Stanford, CA 94304-5718
United States

Leanne M. Williams

Stanford University - Department of Psychiatry and Behavioral Sciences ( email )

401 Quarry Road
Stanford, CA 94304-5718
United States

Government of the United States of America - Sierra Pacific MIRECC

3801 Miranda Ave
Palo Alto, CA 94304
United States

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