Rostral Anterior Cingulate Cortex Morphology Predicts Treatment Response to Internet-Based Cognitive Behavioral Therapy for Depression

Background: Rostral and subgenual anterior cingulate cortex (rACC and sgACC) activity and, to a lesser extent, volume have been shown to predict depressive symptom improvement across different antidepressant treatments. This study extends prior work by examining whether rACC and/or sgACC morphology predicts treatment response to Internet-based cognitive behavioral therapy (iCBT) for major depressive disorder. This is the first study to examine neural predictors of response to iCBT. Methods: Hierarchical linear modeling tested whether pretreatment rACC and sgACC volumes predicted depressive symptom improvement during a six-session (10-week) randomized clinical trial of iCBT (n = 35) versus a monitored attention control condition (n = 38). Analyses also tested whether pretreatment rACC and sgACC volumes differed between patients who achieved depression remission versus patients who did not remit. Results: Larger pretreatment right rACC volume was a significant predictor of greater depressive symptom improvement in iCBT even when controlling for demographic (age, gender, race) and clinical (baseline depression, anhedonia, and anxiety) variables previously linked to treatment response. In addition, pretreatment right rACC volume was larger among patients receiving iCBT whose depression eventually remitted relative to patients who did not remit. Corresponding analyses in the monitored attention control group and for the sgACC were not significant. Conclusions: rACC volume before iCBT demonstrated incremental predictive validity beyond clinical and demographic variables previously found to predict symptom improvement. Such findings may help inform our understanding of the mediating anatomy of iCBT and, if replicated, may suggest neural targets to augment treatment response (e.g., via modulation of rACC function).