Aberrant Temporal Connectivity in Persons at Clinical High Risk for Psychosis

Abstract Background Schizophrenia, a neurodevelopmental disorder, involves abnormalities in functional connectivity (FC) across distributed neural networks, which are thought to antedate the emergence of psychosis. In a cohort of adolescents and young adults at clinical high risk (CHR) for psychosis, we applied data-driven approaches to resting-state functional magnetic resonance imaging data in order to systematically characterize FC abnormalities during this period and to determine whether these abnormalities are associated with psychosis risk and severity of psychotic symptoms. Methods Our analyses included 51 CHR participants and 47 matched healthy control subjects. Of the CHR participants, 12 developed psychosis within 3.9 years. We estimated one multivariate measure of FC and studied its relationship to CHR status, conversion to psychosis, and positive symptom severity. Results Multivariate analyses revealed between-group differences in whole-brain connectivity patterns of bilateral temporal areas, mostly affecting their functional connections to the thalamus. Further, more severe positive symptoms were associated with greater connectivity abnormalities in the anterior cingulate and frontal cortex. Conclusions Our study demonstrates that the well-established FC abnormalities of the thalamus and temporal areas observed in schizophrenia are also present in the CHR period, with aberrant connectivity of the temporal cortex most associated with psychosis risk.