166. Affected Anatomical Rich Club Core and Structural–Functional Integration in Young Offspring of Schizophrenia and Bipolar Disorder Patients

Abstract

Background: Converging evidence suggests that schizophrenia and bipolar disorder include disruptions in the wiring organization of the brain's ana-tomical network, the connectome. As these disorders are genetically medi-ated, offspring of patients constitute an at-risk population. Identifying early neurobiological disturbances in these offspring may help unravel the developmental origins of connectome disruptions observed in established illness and contribute to the development or early detection and intervention strategies. Method(s): This study examined connectome organization in a cohort of 127 nonpsychotic offspring, aged 8 to 18 years (13.5 years on average), of a parent diagnosed with schizophrenia (SZ-offspring; N = 28), bipolar disor-der (BD-offspring; N = 60), and community controls (N = 39). Diffusion-weighted MRI and resting-state fMRI scans were obtained from each participant and processed using well-validated procedures. Anatomical and functional brain networks were reconstructed and examined using graph theoretical analysis. A linear mixed model procedure was used to test group differences in brain network metrics for statistical signifcance, correcting for the effects of age, gender, and within-family dependencies (i.e., siblings) within the subjects' groups. Result(s): An overall group effect was found for anatomical connectivity among the brain's central rich club collective of brain hubs (F = 3.90, P =.023), with SZ-offspring showing defcits rich club connectivity relative to both controls (t =-2.39, P =.018) and BD-offspring (t =-2.61, P =.010). Moreover, in the SZ-offspring, lower levels of anatomical rich club connectivity were associated with higher levels of functional modularity (r =-.59, P =.020), suggesting that defcits in anatomical connectivity among central brain hubs reduce the brain's capacity for intermodular functional integration. Conclusion(s): This study shows lower levels of anatomical rich club connectivity, in association with elevated functional modularity, in non-psychotic young offspring of schizophrenia patients. This fnding suggests that the anatomical integrity of rich club collective is affected in youths with a genetic predisposition for schizophrenia, well before the age at which psychosis typically manifests. Moreover, BD-offspring were found to show unaffected rich club connectivity, suggesting that predisposition for schizophrenia versus bipolar disorder may have a differential effect on the developmental formation of the connectome's central rich club system.