Epigenetic C-reactive protein and corticolimbic gray matter volume in youth at clinical high risk for psychosis.

AIMS: Inflammation and structural brain alterations are implicated in psychosis risk, yet it remains unknown whether epigenetic C-reactive protein (CRP), a DNA methylation-based estimator of cumulative inflammatory burden, is associated with brain structure in youth at clinical high risk for psychosis (CHR-P).

METHODS

We examined associations between epigenetic and plasma CRP, regional gray matter volume (GMV), and positive symptom severity in 165 participants (108 CHR-P, 57 healthy comparisons (HC)) from the North American Prodrome Longitudinal Study Phase 2. Epigenetic CRP was derived from the Illumina 450 k array; plasma CRP was quantified in a subset of 81 participants via multiplex immunoassay. GMVs of the medial prefrontal cortex, anterior cingulate cortex (ACC), and hippocampus were extracted from 3-Tesla MRI scans; positive symptoms were assessed with the Scale of Prodromal Symptoms.

RESULTS

Epigenetic and plasma CRP were weakly correlated (r = 0.19). Higher epigenetic CRP was associated with lower GMV in several corticolimbic regions, including the left caudal ACC (β =  - 0.08, p = 0.011), and lower cACC volume was associated with greater positive symptom severity (β =  - 0.26, p = 0.001). Plasma CRP showed no significant associations in the primary combined-sample model.

CONCLUSIONS

To our knowledge, this study is the first to show that epigenetic CRP is associated with corticolimbic structural differences in CHR-P and HC youth. Epigenetic CRP may capture inflammation-related neurostructural variation relevant to psychosis risk.