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The goals of the current study were to determine the efficacy in major depressive disorder (MDD) of a shortened, computer-augmented cognitive behavioral therapy (CCBT) protocol and to determine brain plasticity effects following CCBT. Seventy-two MDD participants were randomized to CCBT or waitlist control groups and compared to 40 healthy controls (HCs). Functional MRI data were collected for all participants and repeated for patients following CCBT (five therapist-administered manualized CBT sessions plus computer training exercises). Linear mixed-effects models evaluated changes in depression scores throughout treatment and in connectivity from pre- to post-CCBT. Linear regression models compared connectivity differences between groups (MDD vs. HC). Following CCBT, there were decreases in MADRS and BDI (ps < 0.001); there was more negative connectivity of dlPFC with sgACC and DMN with sgACC (ps < 0.002); and there was more positive connectivity of FPN with nucleus accumbens, bilateral amygdalae, bilateral hippocampi, and sgACC and of DMN with ventral and dorsal bilateral anterior insulae (ps < 0.01). There were no associations between change in MADRS and change in connectivity; however, there was an association between change in BDI and change in FPN-sgACC connectivity (p = 0.01). A shortened CBT schedule coupled with home computer exercises was associated with decreased depression symptoms and augmented PFC connectivity with multiple subcortical regions. One possible mechanism of the CCBT intervention is modulating PFC connectivity with subcortical regions, influencing top-down control of affective processes dysregulated in MDD.
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