Altered fronto-amygdalar functional connectivity predicts response to cognitive behavioral therapy in pediatric obsessive-compulsive disorder

Background Based on findings from adults with obsessive-compulsive disorder (OCD), this study examined alterations in resting-state functional connectivity (rs-fc) between the basolateral amygdala (BLA) and the ventromedial prefrontal cortex (vmPFC) in children and adolescents with OCD. We also assessed whether such BLA-vmPFC connectivity changed with or predicted response to exposure and response prevention (E/RP), the first-line treatment for pediatric OCD, given the involvement of these regions in fear processing, regulation, and extinction learning-a probable mechanism of action of E/RP. Methods Resting state functional magnetic resonance imaging scans were acquired from 25 unmedicated, treatment-naive pediatric patients with OCD (12.8 +/- 2.9 years) and 23 age- and sex-matched healthy controls (HCs; 11.0 +/- 3.3 years). Patients completed a 12-16-week E/RP intervention for OCD. Participants were rescanned after the 12-16-week period. ANCOVAs tested group differences in baseline rs-fc. Cross-lagged panel models examined relationships between BLA-vmPFC rs-fc and OCD symptoms pre- and posttreatment. All tests were adjusted for participants' age, sex, and head motion. Results Right BLA-vmPFC rs-fc was significantly reduced (more negative) in patients with OCD relative to HCs at baseline, and increased following treatment. In patients, more positive (less negative) right BLA-vmPFC rs-fc pretreatment predicted greater OCD symptoms reduction posttreatment. Changes in BLA-vmPFC rs-fc was unassociated with change in OCD symptoms pre- to posttreatment. Conclusions These results provide further evidence of the BLA-vmPFC pathway as a potential target for novel treatments or prevention strategies aimed at facilitating adaptive learning and fear extinction in children with OCD or subclinical OCD symptoms.