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Early Change in Neural Circuit Function Engaged by Negative Emotion Mediates Later Depression and Problem-Solving Outcomes Following Behavioural Intervention

19 Pages Posted: 27 Oct 2020

See all articles by Andrea Goldstein-Piekarski

Andrea Goldstein-Piekarski

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

Joseph Wielgosz

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

Lan Xiao

Stanford University - Department of Psychiatry and Behavioral Sciences

Patrick Stetz

Stanford University - Department of Psychiatry and Behavioral Sciences

Carlos Correa

Stanford University - Department of Psychiatry and Behavioral Sciences

Sarah Chang

Stanford University - Department of Psychiatry and Behavioral Sciences

Nan Lv

University of Illinois at Chicago

Lisa G. Rosas

Stanford University - Department of Psychiatry and Behavioral Sciences

Philip Lavori

Stanford University - Department of Psychiatry and Behavioral Sciences

Mark Snowden

University of Washington - Department of Psychiatry and Behavioral Sciences

Elizabeth Venditti

University of Pittsburgh - Department of Psychiatry

Janine Simmons

Government of the United States of America - National Institute of Mental Health

Joshua Smyth

Pennsylvania State University - Departments of Biobehavioral Health and Medicine

Trisha Suppes

Stanford University - Department of Psychiatry and Behavioral Sciences

Megan Lewis

RTI International

Jun Ma

University of Illinois at Chicago - College of Medicine

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: 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.

Keywords: depression, obesity, insula, amygdala, problem-solving, neuroimaging, mediation, behaviour change

Suggested Citation

Goldstein-Piekarski, Andrea and Wielgosz, Joseph and Xiao, Lan and Stetz, Patrick and Correa, Carlos and Chang, Sarah and Lv, Nan and Rosas, Lisa G. and Lavori, Philip and Snowden, Mark and Venditti, Elizabeth and Simmons, Janine and Smyth, Joshua and Suppes, Trisha and Lewis, Megan and Ma, Jun and Williams, Leanne M., Early Change in Neural Circuit Function Engaged by Negative Emotion Mediates Later Depression and Problem-Solving Outcomes Following Behavioural Intervention. Available at SSRN: https://ssrn.com/abstract=3696866 or http://dx.doi.org/10.2139/ssrn.3696866

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

Joseph Wielgosz

Stanford University - Department of Psychiatry and Behavioral Sciences

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

Lan Xiao

Stanford University - Department of Psychiatry and Behavioral Sciences

401 Quarry Road
Stanford, CA 94304-5718
United States

Patrick Stetz

Stanford University - Department of Psychiatry and Behavioral Sciences

401 Quarry Road
Stanford, CA 94304-5718
United States

Carlos Correa

Stanford University - Department of Psychiatry and Behavioral Sciences

401 Quarry Road
Stanford, CA 94304-5718
United States

Sarah Chang

Stanford University - Department of Psychiatry and Behavioral Sciences

401 Quarry Road
Stanford, CA 94304-5718
United States

Nan Lv

University of Illinois at Chicago

1200 W Harrison St
Chicago, IL 60607
United States

Lisa G. Rosas

Stanford University - Department of Psychiatry and Behavioral Sciences

401 Quarry Road
Stanford, CA 94304-5718
United States

Philip Lavori

Stanford University - Department of Psychiatry and Behavioral Sciences

401 Quarry Road
Stanford, CA 94304-5718
United States

Mark Snowden

University of Washington - Department of Psychiatry and Behavioral Sciences

Seattle, WA 98195
United States

Elizabeth Venditti

University of Pittsburgh - Department of Psychiatry

135 N Bellefield Ave
Pittsburgh, PA 15260
United States

Janine Simmons

Government of the United States of America - National Institute of Mental Health

6001 Executive Boulevard, Rm. 7117, MSC 9629
Bethesda, MA 20892
United States

Joshua Smyth

Pennsylvania State University - Departments of Biobehavioral Health and Medicine

University Park
State College, PA 16802
United States

Trisha Suppes

Stanford University - Department of Psychiatry and Behavioral Sciences

401 Quarry Road
Stanford, CA 94304-5718
United States

Megan Lewis

RTI International

PO Box 12194
Washington, DC 20036-3209
United States

Jun Ma

University of Illinois at Chicago - College of Medicine

808 South Wood Street (MC-783) Room 165 CME
Chicago, IL 60612-7302
United States

Leanne M. Williams (Contact Author)

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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