Adaptive cognitive control circuit changes associated with problem-solving ability and depression symptom outcomes over 24 months.

Mechanistically targeted behavioral interventions are a much-needed strategy for improving outcomes in depression, especially for vulnerable populations with comorbidities such as obesity. Such interventions may change behavior and outcome by changing underlying neural circuit function. However, it is unknown how these circuit-level modifications unfold over intervention and how individual differences in early circuit-level modifications may explain the heterogeneity of treatment effects. We addressed this need within a clinical trial of problem-solving therapy for participants with depression symptoms and comorbid obesity, focusing on the cognitive control circuit as a putative neural mechanism of action. Functional magnetic resonance imaging was applied to measure the cognitive control circuit activity at five time points over 24 months. Compared with participants who received usual care, those receiving problem-solving therapy showed that attenuations in cognitive control circuit activity were associated with enhanced problem-solving ability, which suggests that this circuit plays a key role in the mechanisms of problem-solving therapy. Attenuations in circuit activity were also associated with improved depression symptoms. Changes in cognitive control circuit activity at 2 months better predicted changes in problem-solving ability and depression symptoms at 6, 12, and 24 months, with predictive improvements ranging from 17.8 to 104.0%, exceeding baseline demographic and symptom characteristics. Our findings suggest that targeting the circuit mechanism of action could enhance the prediction of treatment outcomes, warranting future model refinement and improvement to pave the way for its clinical application. Editor's summary: Behavioral intervention therapies can improve symptoms of depression but do not work for all patients. To identify brain circuit changes that might underlie treatment response, Zhang et al. performed a longitudinal fMRI imaging study on patients with depression and comorbid obesity who received either problem-solving therapy (I-CARE) or usual care (U-CARE). They found that decreased cognitive control circuit activity measured at different time points over 24 months correlated with better treatment outcomes. A predictive model based on control circuit changes at 2 months outperformed a standard model based on demographic and clinical parameters. These results suggest an approach that could support treatment outcome predictions for depression, but further optimization and validation are needed. —Daniela Neuhofer [ABSTRACT FROM AUTHOR]

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