Altered circuit functional connectivity and associated neural mechanisms of childhood trauma in obsessive-compulsive disorder.

Childhood trauma (CT) has been strongly linked to the course of obsessive-compulsive disorder (OCD), yet the manner in which CT interacts with OCD-related alterations in brain functional connectivity remains unclear. In this study, sixty-six patients with OCD and fifty healthy control participants underwent comprehensive clinical assessments and resting-state functional magnetic resonance imaging. Participants were further categorized according to exposure to childhood trauma, and functional connectivity networks were constructed based on key regions of the cortico-striato-thalamo-cortical (CSTC) circuit to examine the independent and interactive effects of CT and OCD on resting-state connectivity. Both OCD and CT were associated with altered CSTC functional connectivity, although opposite patterns were observed in patients and controls. Specifically, CT exposure in control participants was associated with a reduced density of strong CSTC connections, whereas in patients with OCD, CT was linked to increased connectivity density. Moreover, OCD patients exhibited instability in core network organization, involving the cingulate cortex, orbitofrontal cortex, putamen, and amygdala. Differential analyses revealed that the OCD patients with CT showed increased connectivity compared with both controls with CT (p = 0.005-0.038) and OCD patients without CT (p = 0.002-0.047). Taken together, these findings suggest that CT and OCD jointly modulate CSTC functional connectivity, manifesting as hyperconnectivity and disrupted network organization in OCD patients with a history of childhood trauma, and provide new insights into how early environmental adversity interacts with core neurobiological mechanisms in OCD.