Rich-club connectivity and structural connectome organization in youth at clinical high-risk for psychosis and individuals with early illness schizophrenia.

Abstract

Brain dysconnectivity has been posited as a biological marker of schizophrenia. Emerging schizophrenia connectome research has focused on rich-club organization, a tendency for brain hubs to be highly-interconnected but disproportionately vulnerable to dysconnectivity. However, less is known about rich-club organization in individuals at clinical high-risk for psychosis (CHR-P) and how it compares with abnormalities early in schizophrenia (ESZ). Combining diffusion tensor imaging (DTI) and magnetic resonance imaging (MRI), we examined rich-club and global network organization in CHR-P (n=41) and ESZ (n=70) relative to healthy controls (HC; n=74) after accounting for normal aging. To characterize rich-club regions, we examined rich-club MRI morphometry (thickness, surface area). We also examined connectome metric associations with symptom severity, antipsychotic dosage, and in CHR-P specifically, transition to a full-blown psychotic disorder. ESZ had fewer connections among rich-club regions (ps<.024) relative to HC and CHR-P, with this reduction specific to the rich-club even after accounting for other connections in ESZ relative to HC (ps<.048). There was also cortical thinning of rich-club regions in ESZ (ps<.013). In contrast, there was no strong evidence of global network organization differences among the three groups. Although connectome abnormalities were not present in CHR-P overall, CHR-P converters to psychosis (n=9) had fewer connections among rich-club regions (ps<.037) and greater modularity (ps<.037) compared to CHR-P non-converters (n=19). Lastly, symptom severity and antipsychotic dosage were not significantly associated with connectome metrics (ps<.012). Findings suggest that rich-club and connectome organization abnormalities are present early in schizophrenia and in CHR-P individuals who subsequently transition to psychosis.