Problem-solving therapy-induced amygdala engagement mediates lifestyle behavior change in obesity with comorbid depression: a randomized proof-of-mechanism trial.

Nan Lv, Wesley K Lefferts, Lan Xiao, Andrea N Goldstein-Piekarski, Joseph Wielgosz, Philip W Lavori, Janine M Simmons, Joshua M Smyth, Patrick Stetz, Elizabeth M Venditti, Megan A Lewis, Lisa G Rosas, Mark B Snowden, Olusola A Ajilore, Trisha Suppes, Leanne M Williams, Jun Ma

Journal: The American journal of clinical nutrition 2022;114(6):2060-2073

PMID: 34476464

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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).

Address: Institute of Health Research and Policy, University of Illinois at Chicago, Chicago, IL, USA.; Department of Epidemiology and Population Health, Stanford University, Palo Alto, CA, USA.; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.; Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.; Department of Biomedical Data Science, Stanford University, Stanford, CA, USA.; National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.; Departments of Biobehavioral Health and Medicine, The Pennsylvania State University, University Park, PA, USA.; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Center for Communication Science, RTI International, Seattle, WA, USA.; Department of Epidemiology and Population Health, Stanford University, Palo Alto, CA, USA.; Department of Medicine, Stanford University, Palo Alto, CA, USA.; Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Harborview Medical Center, Seattle, WA, USA.; Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA.; Institute of Health Research and Policy, University of Illinois at Chicago, Chicago, IL, USA.; Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA.

DOI: 10.1093/ajcn/nqab280

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MeSH Terms: Adult, Amygdala, Depression, Humans, Life Style, Obesity, Psychotherapy