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

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).