Sex-specific alterations of intrinsic brain activity and functional connectivity in adolescent obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) often begins during adolescence, yet its neurobiological basis remains unclear. Sex-related heterogeneity may be especially important during this critical developmental period. This study examined sex-specific intrinsic functional alterations in adolescents with OCD. Resting-state functional magnetic resonance imaging data from 50 adolescents with OCD and 50 healthy controls were analyzed. We first tested sex-specific group differences in local brain function using fractional amplitude of low frequency fluctuations (fALFF). Regions showing abnormalities were then used as seeds for whole-brain static functional connectivity (sFC) and dynamic functional connectivity (dFC) subgroup analyses. Finally, associations between functional alterations and symptom severity were assessed. Although no main group effects were observed, significant sex×group interactions were identified in the left insula and right mid-cingulate cortex (MCC). Males with OCD showed reduced insular fALFF, with decreased insula-frontoparietal sFC and reduced insula-orbitofrontal/precuneus dFC. Females with OCD showed increased MCC fALFF, which was positively associated with symptom severity, as well as increased dFC with the precentral gyrus and precuneus. These findings suggest sex-divergent intrinsic functional alterations in adolescent OCD, characterized by an insular-centered pattern in males and an MCC-centered pattern in females, highlighting sex-specific pathophysiological mechanisms during neurodevelopment.