Structural brain volumes of individuals at clinical high risk for psychosis: a meta-analysis

Abstract Background Structural magnetic resonance imaging studies in individuals at clinical high risk for psychosis (CHR) have yielded conflicting results. Methods The aim was to compare intracranial- and structural brain volumes and variability of CHR individuals with those of healthy controls (HCs), and to investigate brain volume differences and variability in CHR subjects with and without transition to psychosis. The PubMed and Embase databases were searched for relevant studies published before June 1st, 2020. Results Thirty-four studies were deemed eligible, which included baseline data of 2111 CHR and 1472 HC participants. Additionally, data was included of 401 CHR subjects who subsequently transitioned to psychosis and 1023 non-transitioned CHR participants. Whole brain and left, right and bilateral hippocampal volume were significantly smaller in CHR subjects compared to HC subjects. Cerebrospinal fluid and lateral ventricle volumes were significantly larger in CHR compared to HC subjects. Variability was not significantly different in CHR compared to HC. CHR individuals with and without subsequent transition to psychosis did not show significant differences in any of the volumetric assessments, nor in variability. Conclusions The current meta-analysis demonstrates reduced whole brain and hippocampal volumes, and increased CSF and lateral ventricle volumes in CHR individuals. However, no significant differences were observed in any of the volumetric assessments between CHR individuals with and without subsequent transition to psychosis. These findings suggest that although structural brain alterations are present before the onset of the disorder, they may not significantly contribute to the identification of CHR individuals at highest risk for the development of psychosis.