Epigenetic management of major psychosis

Abstract

Epigenetic mechanisms are thought to play a major role in the pathogenesis of the major psychoses (schizophrenia and bipolar disorder), and they may be the link between the environment and the genome in the pathogenesis of these disorders. This paper discusses the role of epigenetics in the management of major psychosis: (1) the role of epigenetic drugs in treating these disorders. At present, there are three categories of epigenetic drugs that are being actively investigated for their ability to treat psychosis: drugs inhibiting histone deacetylation; drugs decreasing DNA methylation; and drugs targeting microRNAs; and (2) the role of epigenetic mechanisms in electroconvulsive therapy in these disorders.

Intergenerational Health Responses to Adverse and Enriched Environments

“…Schizophrenia, autism, and intellectual disabilities share similar genetic disruptions linked to specific defects in the development and function of interneurons that otherwise establish inhibitory circuits in the cerebral cortex (39). These observations indicate that effective prevention and treatment may be found through influencing these links in the causal chain, possibly through nutrition and medication (45). The transgenerational behavior of schizophrenia, the severity of which worsens over generations, may be based not only on epigenetic mechanisms associated with gametic epigenetic inheritance but also on expansion of marks in the methylation-promoting genomic regions within generations (50).…”

Impact of childhood adversities on the short-term course of illness in psychotic spectrum disorders

“…Schizophrenia Psychiatric GWAS Consortium, 2011;Svrakic et al, 2013;Graux et al, 2014), while the modulating role of childhood adversities seems less clear. Early-life stress is thought to influence neuronal development (Andersen et al, 2008;Murgatroyd et al, 2009) and neuroendocrine response (Heim et al, 2000) as well as epigenetic imprinting (Peedicayil 2011;Shonkoff et al, 2012;Svrakic et al, 2013), thereby interacting in a complex manner with genetic and epigenetic factors.…”

Epigenetic approaches for bipolar disorder drug discovery

“…There is increasing evidence that there are abnormalities in epigenetic mechanisms of gene expression predisposing to the development of non-organic psychiatric disorders such as schizophrenia and BD [5,6,12]. These epigenetic abnormalities are thought to involve DNA methylation, histone modifications and RNA-mediated regulation of gene expression.…”

“…These epigenetic abnormalities are thought to involve DNA methylation, histone modifications and RNA-mediated regulation of gene expression. However, at present, no such epigenetic abnormality has been definitively identified [5,6].…”

“…However, to date, no genetic mutation or polymorphism predisposing to the pathogenesis of BD has been definitively identified [4]. It has also been suggested that epigenetic mechanisms of gene expression could be involved in the inheritance of BD [5,6]. Epigenetics literally means above or in addition to genetics and involves molecular mechanisms such as DNA methylation, modifications of histones, RNAmediated regulation of gene expression, chromatin remodeling and the use of modified histones [7].…”