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

Abstract

Previous studies of imaging predictors on acute treatment response in late-life depression (LLD) demonstrated that poor response to selective serotonin reuptake inhibitors (SSRIs) 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. Thirty-six older major depressive disorder (MDD) patients not currently on antidepressant treatment had a baseline, pre-treatment resting-state functional magnetic resonance imaging scan, followed by sertraline treatment for 12weeks. Depression severity was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). Subjects whose MADRS score decreased less than 50% from baseline or who discontinued sertraline for any reason were classified as nonresponders (n=21). Subjects whose 12-week MADRS score dropped greater than or equal to 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 false discovery rate (FDR) correction for multiple comparisons. Relative to the responder group, the nonresponder 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 nonresponder group. 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 LLD.