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-naïve 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 post-treatment. 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 pre-treatment predicted greater OCD symptoms reduction post-treatment. Changes in BLA-vmPFC rs-fc was unassociated with change in OCD symptoms pre- to post-treatment. 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.