Brain Activation Associated With Response to Psychotherapies for Late-Life Depression: A Task-Based fMRI Study.

Background: The course of late-life depression is associated with functioning of multiple brain networks. Understanding the brain mechanisms associated with response to psychotherapy can inform treatment development and a personalized treatment approach. This study examined how activation of key regions of the salience network, default mode network and reward systems is associated with response to psychotherapies for late-life depression.

Methods: Thirty-three older adults with major depressive disorder were randomized to 9 weeks of Engage or Problem-Solving Therapy for late-life depression. Participants completed a Probabilistic Reversal Learning task in the MRI at baseline and Week 6. We focused on focal activation in regions of interest selected a priori: the subgenual cingulate cortex (sgACC; DMN); the dorsal anterior cingulate cortex (dACC; salience network and reward system); and the nucleus accumbens (NAcc; reward system). We applied mixed-effects regression models to examine whether brain activation was associated with psychotherapy response.

Results: We found that at baseline, low activation of the dACC and the sgACC was associated with lower depression severity over 6 weeks of psychotherapy. In addition, we observed significant time*activation interactions, such that after 6 weeks of psychotherapy, lower dACC activation and higher NAcc and sgACC activation were each associated with lower depression severity. Further, we found that baseline slower response to negative feedback and faster response to positive feedback was associated with lower depression severity over 6 weeks of psychotherapy.

Conclusions: Our findings suggest that activation of reward, salience, and DMN regions may serve as markers of response during psychotherapy for late-life depression. Engagement of these networks may be linked to treatment outcome. Personalized psychotherapies can target individuals' brain profiles to improve outcomes for older adults with major depression.

Article summary: This study examined whether activation of regions of the reward, salience and default mode networks is associated with response to psychotherapies for late-life depression. We found that baseline low activation of the dACC and the sgACC was associated with lower depression severity during psychotherapy. We also found that at week 6, lower dACC activation and higher NAcc and sgACC activation were linked with lower depression severity. These regions may represent promising brain mechanisms for future personalized interventions.