DNA methylation levels of RELN promoter region in ultra-high risk, first episode and chronic schizophrenia cohorts of schizophrenia

The essential role of the Reelin gene (RELN) during brain development makes it a prominent candidate in human epigenetic studies of Schizophrenia. Previous literature has reported differing levels of DNA methylation (DNAm) in patients with psychosis. Therefore, this study aimed to (1) examine and compare RELN DNAm levels in subjects at different stages of psychosis cross-sectionally, (2) analyse the effect of antipsychotics (AP) on DNAm, and (3) evaluate the effectiveness and applicability of RELN promoter DNAm as a possible biological-based marker for symptom severity in psychosis. The study cohort consisted of 56 healthy controls, 87 ultra-high risk (UHR) individuals, 26 first-episode (FE) psychosis individuals and 30 chronic schizophrenia (CS) individuals. The Positive and Negative Syndrome Scale (PANSS) was used to assess Schizophrenia severity. After pyrosequencing selected CpG sites of peripheral blood, the Average mean DNAm levels were compared amongst the 4 subgroups. Our results showed differing levels of DNAm, with UHR having the lowest (7.72 ± 0.19) while the CS had the highest levels (HC: 8.78 ± 0.35; FE: 7.75 ± 0.37; CS: 8.82 ± 0.48). Significantly higher Average mean DNAm levels were found in CS subjects on AP (9.12 ± 0.61) compared to UHR without medication (UHR(−)) (7.39 ± 0.18). A significant association was also observed between the Average mean DNAm of FE and PANSS Negative symptom factor (R² = 0.237, ß = −0.401, *p = 0.033). In conclusion, our findings suggested different levels of DNAm for subjects at different stages of psychosis. Those subjects that took AP have different DNAm levels. There were significant associations between FE DNAm and Negative PANSS scores. With more future experiments and on larger cohorts, there may be potential use of DNAm of the RELN gene as one of the genes for the biological-based marker for symptom severity in psychosis.