Abstract
So far, genetic studies of treatment response in schizophrenia, bipolar disorder, and major depression have returned results with limited clinical utility. A gene × environment interplay has been proposed as a factor influencing not only pathophysiology but also the treatment response. Therefore, epigenetics has emerged as a major field of research to study the treatment of these three disorders. Among the epigenetic marks that can modify gene expression, DNA methylation is the best studied. We performed a systematic search (PubMed) following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA guidelines for preclinical and clinical studies focused on genome-wide and gene-specific DNA methylation in the context of schizophrenia, bipolar disorders, and major depressive disorder. Out of the 112 studies initially identified, we selected 31 studies among them, with an emphasis on responses to the gold standard treatments in each disorder. Modulations of DNA methylation levels at specific CpG sites have been documented for all classes of treatments (antipsychotics, mood stabilizers, and antidepressants). The heterogeneity of the models and methodologies used complicate the interpretation of results. Although few studies in each disorder have assessed the potential of DNA methylation as biomarkers of treatment response, data support this hypothesis for antipsychotics, mood stabilizers and antidepressants.
Highlights
Schizophrenia, bipolar disorder, and major depressive disorder are severe mental illnesses (SMI) defined by classifications such as Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and International Classification of Diseases (ICD10), of sufficient duration to meet diagnostic criteria and resulting in significant functional impairment [1]
We identified 112 articles on the basis of their titles; 67 abstracts focused on DNA methylation as a biomarker of treatment response in cellular or rodent models, or in bipolar disorder (BD), SCZ and/or major depressive disorder (MDD) patients were selected
Recent data in high-risk offspring from BD patients suggest that the observed differences in DNA methylation are directly related to the familial environment [98]
Summary
Schizophrenia, bipolar disorder, and major depressive disorder are severe mental illnesses (SMI) defined by classifications such as Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and International Classification of Diseases (ICD10), of sufficient duration to meet diagnostic criteria and resulting in significant functional impairment [1]. SCZ, BD, and MDD are characterized by acute episodes including psychotic, depressive, and/or manic features that are superimposed, in some patients, with a chronic course that mainly includes negative symptoms in SCZ and potential cognitive decline in these three SMI. Even though these disorders are defined as separated entities, their clinical boundaries remain unclear as they share common symptomatic and functional impairments. Abnormalities in neurocognitive functioning are associated with BD and SCZ [8] Psychotic symptoms, such as delusions or hallucinations predominantly associated with SCZ, are frequently experienced by patients during severe mood episodes belonging to BD or MDD [9]. SMI reduce patients’ life expectancy by 10 to 20 years [11], emphasizing the need for a better stratification of patients and identification of patients that are more likely to respond to a given treatment
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