Corticostriatal connectivity in monozygotic twin pairs discordant for obsessive-compulsive disorder

Traditional case-control studies show that obsessive-compulsive disorder (OCD) is associated with disturbances in cortico-striatal-thalamo-cortical (CSTC) brain circuits. Whether these findings represent underlying familial vulnerabilities (i.e. shared genetic and environmental factors) or are the result of acquired non-shared environmental influences, such as chronic stress or lifestyle factors, is unknown. Using a unique sample of monozygotic twin pairs discordant for lifetime OCD diagnoses (14 pairs, 28 twins) and resting-state functional MRI, we examined the contribution of non-shared environmental influences to CSTC functional connectivity while strictly controlling for shared genetic and environmental factors. Further, we examined familial vulnerability effects by comparing the unaffected co-twins of OCD-affected twins to a sample of control twins (14 pairs, 28 twins). Non-shared environmental influences were statistically significantly associated with thalamostriatal hypoconnectivity, whereas familial vulnerability was significantly associated with heightened connectivity between the striatum and the medial orbitofrontal cortex. These findings suggest that non-shared environmental and familial factors may differentially relate to distinct CSTC circuit disturbances in OCD.