Abnormal Rich-Club Organization Associated with Compromised Cognitive Function in Patients with Schizophrenia and Their Unaffected Parents

Schizophrenia is considered to be a disorder of brain connectivity, which might result from a disproportionally impaired rich-club organization. The rich-club is composed of highly interconnected hub regions that play crucial roles in integrating information between different brain regions. Few studies have yet investigated whether the structural rich-club organization is impaired in patients and their first-degree relatives. In this study, we established a weighted network model of white matter connections using diffusion tensor imaging of 19 patients and 39 unaffected parents, 22 young healthy controls for the patients, and 25 old healthy controls for the parents. Feeder edges between rich-club nodes and non-rich-club nodes were significantly decreased in both schizophrenic patients and their unaffected parents compared with controls.Furthermore, the feeder edges showed significant positive correlations with the scores in Category Fluency Test—animal naming in the unaffected parents. Specific feeder edges exhibited discriminative power with accuracy of 84.4% in distinguishing unaffected parents from old healthy controls. Our findings suggest that impaired richclub organization, especially impaired feeder edges, may be related to familial vulnerability to schizophrenia,possibly reflecting a genetic predisposition for schizophrenia.