DNA hypermethylation of serotonin transporter gene promoter in drug naïve patients with schizophrenia

Abstract

A correlation between reduction in 5-HTT expression and DNA hypermethylation of the 5-HTT promoter in drug naïve SCZ patients suggests that an epigenetically defined hypo-activity of 5-HTT may be linked to SCZ pathogenesis. Furthermore, this epigenetic mark in DNA extracted from saliva can be considered as one of the key determinants in a panel of diagnostic and/or therapeutic biomarkers for SCZ.

An Update on the Epigenetics of Psychotic Diseases and Autism

“…Furthermore, gene-specific methylation analysis using a larger sample size of 468 individuals, uncovered hypermethylation of glucocorticoid receptor gene (NR3C1) in blood from adolescents affected by traumatic stress or stressful life events in childhood [32]. Although blood or saliva cells are not the most appropriate surrogates for the brain cells affected in psychiatric diseases, recent genomewide studies [4,5] support the previous findings of genespecific promoter DNAM analyses [33][34][35] indicating that some of the epigenetic alterations of brain cells are reflected in peripheral tissues. Additionally, an animal study found that, the blood DNAM changes of FKBP5 involved in the development of major depression following the exposure to traumatic events [36] is representative of the dynamics of glucocorticoid-induced DNAM alterations in the brain [37].…”

“…The next breakthrough came from the most recent genespecific DNAM analyses which identified promoter DNA hypermethylation of 5-HTT (SLC6A4) in the saliva and postmortem brains of patients with SCZ and hypermethylation of BDNF promoter in blood and reduced expression of A2AR (ADORA2A) associated with DNA hypermethylation in postmortem brains of SCZ patients [33,[48][49]. Confirmation of the initial observations of promising genes in subsefuture science group An update on the epigenetics of psychotic diseases & autism Review quent studies along with corresponding expression is shown in Table 2.…”

Epigenetic Factors in Schizophrenia: Mechanisms and Experimental Approaches

“…For example, a recent study (41 cases, 46 controls) across 4 brain regions found many genome regions that displayed differentially methylated DNA [28], while a larger study (689 cases, 645 controls) using blood samples similarly identified many differentially methylated loci [29]. Other studies support the importance of DNA cytosine methylation in schizophrenia [30-32]. Differential DNA methylation studies to date have mapped to major neurotransmitter pathways.…”

Genomics and epigenomics in novel schizophrenia drug discovery: translating animal models to clinical research and back

“…Genome-wide DNA methylation profiling Significant differences in DNA methylation at multiple loci [80] 69/63 Brain tissue CHRM1 Hypomethylation [81] 80/71 Peripheral blood BDNF Hypomethylation [82] 35/35 30/30…”

“…So far, few studies have examined the epigenetic effects of antipsychotics directly in humans and results are far from being clear, as detailed in Table 3 [65,78,82,86]. Patients treated with haloperidol showed a level of global methylation almost normal (control-like), as if the drug may partially rescue global hypomethylation reported in schizophrenia [65].…”