DNA Methylation and Schizophrenia: Current Literature and Future Perspective

Abstract

Schizophrenia is a neuropsychiatric disorder characterized by dissociation of thoughts, idea, identity, and emotions. It has no central pathophysiological mechanism and precise diagnostic markers. Despite its high heritability, there are also environmental factors implicated in the development of schizophrenia. Epigenetic factors are thought to mediate the effects of environmental factors in the development of the disorder. Epigenetic modifications like DNA methylation are a risk factor for schizophrenia. Targeted gene approach studies attempted to find candidate gene methylation, but the results are contradictory. Genome-wide methylation studies are insufficient in literature and the available data do not cover different populations like the African populations. The current genome-wide studies have limitations related to the sample and methods used. Studies are required to control for these limitations. Integration of DNA methylation, gene expression, and their effects are important in the understanding of the development of schizophrenia and search for biomarkers. There are currently no precise and functional biomarkers for the disorder. Several epigenetic markers have been reported to be common in functional and peripheral tissue. This makes the peripheral tissue epigenetic changes a surrogate of functional tissue, suggesting common epigenetic alteration can be used as biomarkers of schizophrenia in peripheral tissue.

Using animal models for the studies of schizophrenia and depression: The value of translational models for treatment and prevention

“…In particular, the abnormal behavioral phenotypes of the MAM model are developed through extended trajectories consistent with the natural history of schizophrenia, with alterations related to positive symptoms that tend to manifest later compared to social withdrawal and cognitive deficits ( Gomes et al, 2016 ). In addition, in utero MAM exposure is known to induce widespread, long-lasting DNA ( Perez et al, 2016 ) and histone hypermethylation ( Maćkowiak et al, 2014 ), which are factors supported by recent epigenetics research to be potential molecular links between genetic and environmental risk factors ( Magwai et al, 2021 ). This gives the MAM model additional construct validity and valuable research potential, such as to identify hypermethylated genes that contribute to distinct behavioral or circuit alterations [example studies, see: Gulchina et al (2017) ].…”

Predictive Biomarkers for Antipsychotic Treatment Response in Early Phase of Schizophrenia: Multi-Omic Measures Linking Subcortical Covariant Network, Transcriptomic Signatures, and Peripheral Epigenetics

“…Another unsolved issue is that less is known about whether the variance of subcortical morphological connectivity is driven by gene expression patterns and epigenetic mechanisms, which are the plausible molecular basis of phenotypic heterogeneity across individuals with schizophrenia. Epigenetic modifications are proposed to mediate between environmental insults and gene expression and alter and stably maintain the expression of genes ( Magwai et al, 2021 ). DNA methylation (DNAm) is the most widely explored epigenetic mechanism and has been suggested to be associated with an antipsychotic drug action mechanism ( Ovenden et al, 2018 ).…”

ABCB9 polymorphism rs61955196 is associated with schizophrenia in a Chinese Han population

“…DNA methylation is a heritable epigenetic modification which alters gene expression[ 4 ]. Studies have demonstrated that overall DNA hypomethylation is evident in SCZ patients, while treatment with haloperidol might increase methylation[ 5 , 6 ]. In other words, DNA methylation, which can regulate gene expression, is closely associated with the risk of SCZ [ 7 - 10 ].…”