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 (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. METHODS: 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 12 weeks. 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. RESULTS: 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. 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 LLD.
Emam, H; Steffens, DC; Pearlson, GD; Wang, L
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