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

Abstract

BackgroundChoroid plexus (ChP) enlargement exists in first-episode and chronic psychosis, but whether enlargement occurs before psychosis 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, neuroanatomical, and plasma analytes. MethodsClinical and neuroimaging data from the North American Prodrome Longitudinal Study 2 (NAPLS2) was used for analysis. 509 participants (169 controls, 340 CHR) were recruited. Conversion status was determined after 2-years of follow-up, with 36 psychosis converters. The lateral ventricle ChP was manually segmented from baseline scans. A subsample of 31 controls and 53 CHR had plasma analyte and neuroimaging data. ResultsCompared to controls, CHR (d=0.23, p=0.017) and non-converters (d=0.22, p=0.03) demonstrated higher ChP volumes, but not in converters. In CHR, greater ChP volume correlated with lower cortical (r=-0.22, p<0.001), subcortical gray matter (r=-0.21, p<0.001), and total white matter volume (r=-0.28,p<0.001), as well as larger lateral ventricle volume (r=0.63,p<0.001). Greater ChP volume correlated with makers functionally associated with the lateral ventricle ChP in CHR [CCL1 (r=-0.30, p=0.035), ICAM1 (r=0.33, p=0.02)], converters [IL1{beta} (r=0.66, p=0.004)], and non-converters [BMP6 (r=-0.96, p<0.001), CALB1 (r=-0.98, p<0.001), ICAM1 (r=0.80, p=0.003), SELE (r=0.59, p=0.026), SHBG (r=0.99, p<0.001), TNFRSF10C (r=0.78, p=0.001)]. ConclusionsCHR and non-converters demonstrated significantly larger ChP volumes compared to controls. Enlarged ChP was associated with neuroanatomical alterations and analyte markers functionally associated with the ChP. These findings suggest that the ChP may be a key explanatory biomarker in CHR for psychosis.