Linking Choroid Plexus Enlargement with Plasma Analyte and Structural Phenotypes in Clinical High Risk for Psychosis: A Multisite Neuroimaging Study

Abstract

AbstractBackgroundChoroid plexus (ChP) enlargement has been described in first-episode psychosis and psychosis spectrum disorders, but whether ChP enlargement occurs before disease onset is unknown. This study investigated whether ChP volume is enlarged in individuals with clinical high-risk (CHR) for psychosis and whether these changes are related to clinical, cortical, and plasma analyte measures.MethodsClinical and neuroimaging data from the North American Prodrome Longitudinal Study 2 (NAPLS2) was used for analysis. A total of 509 participants (169 controls, 340 CHR) were recruited across 8 sites. Conversion status was determined until 2-years of follow-up, with 36 patients developing psychosis. The lateral ventricle ChP was manually segmented from all available baseline brain scans. A subsample of 84 participants (31 controls, 53 CHR) had plasma analyte and neuroimaging data.ResultsCompared to controls, CHR overall (d=0.22, p=0.017) and converters(d=0.21, p=0.041)demonstrated higher ChP volumes, but not nonconverters. In CHR, greater ChP volume correlated with lower cortical(r=−0.22, p<0.001)and subcortical gray matter volume(r=− 0.21, p<0.001), total white matter volume(r=−0.28,p<0.001), and larger lateral ventricle volume(r=0.63,p<0.001). In CHR, greater ChP volume, but not lateral ventricle volume, correlated with higher C3(r=0.39, p=0.005)and TSH(r=0.31, p=0.026), and lower MMP7(r=−0.30, p=0.032)and UMOD(r=−0.33, p=0.019).Conclusions and RelevanceCHR and converters to psychosis demonstrated significantly larger ChP volumes compared to controls. ChP enlargement was associated with cortical volume reduction and increased peripheral inflammatory markers. These findings suggest that the ChP may be a key biomarker in psychosis disease onset and conversion.