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Background: Previous magnetic resonance imaging (MRI) studies in patients with schizophrenia have demonstrated reduced cortical thickness predominantly in the fronto-temporal regions, but several MRI studies of regional cortical thickness in individuals at clinical high-risk for psychosis have reported inconsistent results. In addition, it remains elusive whether abnormalities of the cortical thickness in individuals at risk of psychosis, if present, are related to their functional outcome. Methods: T1-weighted structural MR scans were obtained from 107 individuals with at-risk mental state (ARMS), of whom 21 (19.6%) later developed psychosis during clinical follow-up (mean = 4.9  years, SD = 2.6 years), as well as 104 age- and gender- matched healthy control subjects recruited at 4 scanning sites (University of Toyama, Toho University, Tohoku University, and The University of Tokyo). ARMS individuals were subdivided into good (ARMS-G, n = 77) and poor (ARMS-P, n = 13) outcome groups based on the Global Assessment of Functioning (GAF) scores both at baseline and 1-year follow-up. After preprocessing MR images using FreeSurfer software (ver.5.3.), we continuously measured the cortical thickness of entire cortex. A general linear model controlling for age, gender, and sites was used to estimate group differences. To correct for multiple comparisons, a Monte Carlo simulation procedure was used. This study was approved by the Committees on Medical Ethics of each site. After a complete description of the study was provided, written informed consent was obtained from all subjects. Results: Compared with the controls, ARMS individuals exhibited significantly reduced cortical thickness in the superior and inferior frontal gyri, parahippocampal gyri, fusiform gyri, temporal pole cortices, and insula cortices bilaterally, as well as in the left middle frontal gyrus and right precuneus cortex. ARMS individuals also showed significantly increased cortical thickness in the left pre- and postcentral gyrus and right pericalcarine cortex in comparison to the controls. Within ARMS population, ARMS-P individuals had significantly reduced cortical thickness in the right paracentral lobule compared with ARMS-G individuals. Discussion: Cortical thinning in the fronto-temporal regions as well as cortical thickening in the posterior cortices seen in ARMS individuals might be associated with general vulnerability to psychopathology. Furthermore, cortical thickness of the right paracentral lobule could be a predictive marker for functional outcome in ARMS population. [ABSTRACT FROM AUTHOR]