Resting State Functional Connectivity and Outcomes of Psychotherapies for Late-life Depression

Background: Problem solving therapy (PST) and “Engage”, a reward-exposure” based therapy, are important treatment options for late-life depression, given modest efficacy of antidepressants in this disorder. Abnormal function of the reward and default mode networks has been observed during depressive episodes. This study examined whether resting state functional connectivity (rsFC) of reward and DMN circuitries is associated with treatment outcomes. Methods: Thirty-two older adults with major depression (mean age = 72.7) were randomized to 9-weeks of either PST or “Engage”. We assessed rsFC at baseline and Week 6. We placed seeds in three a priori regions of interest: subgenual cingulate (sgACC), dorsal anterior cingulate cortex (dACC), and nucleus accumbens (NAcc). Outcome measures included the Hamilton Depression Rating Scale (HAMD) and the Behavioral Activation for Depression Scale (BADS).Results: In both PST and “Engage”, higher rsFC between the sgACC and middle temporal gyrus at baseline was associated with greater improvement in depression severity (HAMD). Preliminary findings suggested that in “Engage” treated participants, lower rsFC between the dACC and DMPFC at baseline was associated with HAM-D improvement. Finally, in Engage only, increased rsFC from baseline to Week 6 between NAcc and Superior Parietal Cortex was associated with increased BADS scores.Conclusion: The results suggest that patients who present with higher rsFC between the sgACC and a structure within the DMN may benefit from behavioral psychotherapies for late life depression. ‘Engage’ may lead to increased rsFC within the reward system reflecting a reconditioning of the reward systems by reward exposure.