DNA methylation pattern of gene promoters of major neurotransmitter systems in older patients with schizophrenia with severe and mild cognitive impairment

Abstract

Objective: To analyze, in older patients with schizophrenia, the methylation status of a set of genes associated with the pathophysiology of the disorder but including anatomical, clinical, and cognitive criteria in the experimental design that, in conjunction with the epigenetic status of specific genes, allows us to derive an integrative model.

Method: This study included 29 human brain samples from older schizophrenic patients with severe and mild cognitive impairment. We administered a comprehensive battery of neurocognitive tests to determine the size of the impairment across different cognitive domains. We focused our study on the analysis of the methylation pattern of 19 genes of major neurotransmitter systems using methylation-specific PCR and bisulfite genomic sequencing.

Results: Our results highlight an absence of hypermethylation and hypomethylation in older patients with schizophrenia and in healthy controls, irrespective of the degree of the cognitive deficit measured in the neuropsychological assessment (Fisher's exact test; p<0.05).

Conclusion: mRNA or protein expression level differences in genes of major neurotransmitter systems that are known to be altered in schizophrenia must be because of regulatory mechanisms other than the DNA methylation of its promoter regions, although our results highlight the idea that the analysis of the epigenetic mechanisms involved in schizophrenia represents a new approach that has the possibility of uncovering molecular mechanisms of dysregulated gene expression in this complex disorder.

Keywords: DNA methylation; cognition; epigenetics; older schizophrenia.