Increased ventromedial prefrontal cortex activity and connectivity predict poor sertraline treatment outcome in late-life depression.

OBJECTIVE: Previous studies of imaging predictors on acute treatment response in late life depression (LLD) demonstrated that poor response to selective serotonin reuptake inhibitors (SSRI) is associated with pre-treatment low functional connectivity (FC) within executive control network and high FC within default-mode network including the ventromedial prefrontal cortex (vmPFC). However, there is less research in regional resting-state functional activity that explains FC changes related to SSRI response.

METHODS: Thirty-six older MDD patients not currently on antidepressant treatment had a baseline, pre-treatment resting state functional magnetic resonance imaging scan, followed by sertraline treatment for 12 weeks. Depression severity was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). Subjects whose MADRS score decreased < 50% from baseline or who discontinued sertraline for any reason were classified as non-responders (n=21). Subjects whose 12-week MADRS score dropped ≥ 50% from baseline were defined as responders (n=15). We conducted the amplitude of low-frequency fluctuation (ALFF) and region of interest (ROI)-to-ROI FC analyses independently. Significance threshold was set at p<0.05 with FDR correction for multiple comparisons.

RESULTS: Relative to the responder group, the non-responder group showed significantly less ALFF in the dorsomedial prefrontal cortex (dmPFC), and greater ALFF in the vmPFC/subgenual cingulate area. For ROI-to-ROI connectivity, there was significantly greater connectivity between the vmPFC and the cerebellar vermis in the non-responder group. ​ CONCLUSION: Our study highlighted the association of vmPFC resting state activity and connectivity with SSRI response. Future studies are warranted for understanding the role of vmPFC-vermis connectivity in late-life depression.