DNA methylation in peripheral tissue of schizophrenia and bipolar disorder: a systematic review

Abstract

BackgroundIncreasing evidence suggests the involvement of epigenetic processes in the development of schizophrenia and bipolar disorder, and recent reviews have focused on findings in post-mortem brain tissue. A systematic review was conducted to synthesise and evaluate the quality of available evidence for epigenetic modifications (specifically DNA methylation) in peripheral blood and saliva samples of schizophrenia and bipolar disorder patients in comparison to healthy controls.MethodsOriginal research articles using humans were identified using electronic databases. There were 33 included studies for which data were extracted and graded in duplicate on 22 items of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement, to assess methodological precision and quality of reporting.ResultsThere were 15 genome-wide and 18 exclusive candidate gene loci investigations for DNA methylation studies. A number of common genes were identified as differentially methylated in schizophrenia/bipolar disorder, which were related to reelin, brain-derived neurotrophic factor, dopamine (including the catechol-O-methyltransferase gene), serotonin and glutamate, despite inconsistent findings of hyper-, hypo-, or lack of methylation at these and other loci. The mean STROBE score of 59 % suggested moderate quality of available evidence; however, wide methodological variability contributed to a lack of consistency in the way methylation levels were quantified, such that meta-analysis of the results was not possible.ConclusionsModerate quality of available evidence shows some convergence of differential methylation at some common genetic loci in schizophrenia and bipolar disorder, despite wide variation in methodology and reporting across studies. Improvement in the clarity of reporting clinical and other potential confounds would be useful in future studies of epigenetic processes in the context of exposure to environmental and other risk factors.

The role of DNA methylation in the pathophysiology and treatment of bipolar disorder

“…This might be due to the lack of control for genotype, differences in the tissue being analyzed, sample heterogeneity, as well as still insufficient sample sizes. The variability between studies has also been pointed out by a recent systematic review (Teroganova et al, 2016) of findings in peripheral tissues (blood and saliva), especially in regards to the different methods used for the assessment of DNA methylation, DNA extraction, and lack of control for potential effects of clinical variables (such as diet, exercise, smoking, and ethnicity).…”

Effect of Clozapine on DNA Methylation in Peripheral Leukocytes from Patients with Treatment-Resistant Schizophrenia

“…DNA methylation mainly occurs at the 5′ position of the cytosine base followed by a guanine base that is called CpG [9]. A number of studies have demonstrated aberrant DNA methylation in SCZ [10,11,12,13,14,15,16,17,18]. Furthermore, growing evidence suggests that DNA methylation may be involved in the therapeutic efficacy of atypical antipsychotic drugs [19,20,21,22,23,24].…”

Differential SLC1A2 Promoter Methylation in Bipolar Disorder With or Without Addiction

“…Approaches to study epigenetic signatures in humans involve both studies of post-mortem brains but also peripheral tissues (blood and saliva) (Teroganova et al, 2016). In comparison to other major psychiatric disorders (i.e., schizophrenia and major depressive disorder) epigenetic contributions to various BD phenotypes remains largely understudied.…”