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.