DNA hyper-methylation associated with schizophrenia may lead to breakdown of self-tolerance

Abstract Environmental stressors have effects on the genomic DNA methylation patterns of B lymphocytes in schizophrenia (SCZ), which may therefore perturb the immune homeostasis and trigger autoimmune responses. This study aimed to investigate the global genomic DNA methylation differences in remitters of SCZ (RSCZ) and non-remitters of SCZ (NRSCZ), further their effects on autoimmune responses of target genes. A total of 2722 Chinese Han origin subjects were recruited, including a follow-up cohort and a cross-sectional cohort. We found a DMS of cg14341177 in SCZ which inhibit the mRNA alternative splicing of BICD2, further leading to increased plasma anti-BICD2 IgG autoantibody levels. The levels of cg14341177 methylation and anti-BICD2 IgG decreased significantly in the endpoint samples of RSCZ, but not in NRSCZ. There are strong positive correlations between cg14341177 methylation, anti-BICD2 IgG, and PANSS scores. These data suggest that cg14341177 methylation and anti-BICD2 IgG levels may potentially serve as useful biomarkers.