The relationship of childhood trauma and DNA methylation of NMDA receptor genes in first-episode schizophrenia.

ABSTRACT

Aim: We investigated GRIN1, GRIN2A, GRIN2B and LINE-1 DNA methylation in first-episode schizophrenia patients, their nonaffected siblings and age- and sex-matched controls testing for associations between DNA methylation and exposition to childhood trauma. Materials & methods: The Childhood Trauma Questionnaire evaluated the history of childhood trauma. Genomic DNA was bisulfite converted and pyrosequencing was employed to quantify DNA methylation. Results:GRIN2A, GRIN2B and LINE-1 DNA methylation was not associated with childhood trauma in patients, siblings and controls. Siblings with childhood trauma had hypermethylation at CpG1 of GRIN1 compared with siblings without trauma. Conclusion: Childhood trauma may influence GRIN1 methylation in subjects with liability to psychosis, but not in frank schizophrenia or controls.

Lay abstract Schizophrenia results from a combination of genetic and environmental influences. We investigated how some changes in genes can be silenced by a process named DNA methylation and may be linked to schizophrenia. For this reason, we hypothesized that childhood trauma, an environmental risk factor, would be associated with DNA methylation in schizophrenia patients compared with their unaffected siblings and controls. Our research has shown that altered blood DNA methylation of one candidate gene for psychiatric disorders may be associated with childhood trauma in the unaffected siblings of schizophrenia patients, but not in frank schizophrenia or controls. We believe that this gene plays an important role in helping identify vulnerable as well as resilient individuals to schizophrenia disorder.