Epigenetic mechanisms in schizophrenia

Abstract

Epigenetic modifications, including DNA methylation, histone modifications, and non-coding RNAs, have been implicated in a number of complex diseases. Schizophrenia and other major psychiatric and neurodevelopmental disorders are associated with abnormalities in multiple epigenetic mechanisms, resulting in altered gene expression during development and adulthood. Polymorphisms and copy number variants in schizophrenia risk genes contribute to the high heritability of the disease, but environmental factors that lead to epigenetic modifications may either reduce or exacerbate the expression of molecular and behavioral phenotypes associated with schizophrenia and related disorders. In the present paper, we will review the current understanding of molecular dysregulation in schizophrenia, including disruption of the dopamine, NMDA, and GABA signaling pathways, and discuss the role of epigenetic factors underlying disease pathology.

Neurological dysfunctions associated with altered BACE1‐dependent Neuregulin‐1 signaling

“…; Fromer et al . ; Ibi and Gonzalez‐Maeso ; Shorter and Miller ). An association study of SCZ families in Iceland initially revealed Nrg1 to be a SCZ‐susceptible gene (Stefansson et al .…”

DNA methylation regulates gabrb2mRNA expression: developmental variations and disruptions in l‐methionine‐induced zebrafish with schizophrenia‐like symptoms

“…Keywords: Behavioral deficits, developmental variations, GABAergic system, gabrb2, genome-wide DNA methylation, MET, mRNA expression, promoter DNA methylation, schizophrenia, zebrafish Received 6 April 2016, revised 18 July 2016, accepted for publication 4 August 2016 Psychiatric disorders are a diverse group of diseases that affect mental functions, including thinking, feeling, mood and sociability, and they are caused by interactions among multiple genes and environmental and epigenetic factors (Norton 2013). Schizophrenia is a severe psychiatric disorder that is often characterized by positive symptoms, such as hallucinations, psychosis and mania, as well as negative symptoms, including anhedonia and social withdrawal (Shorter & Miller 2015). Several neurotransmitters may contribute to schizophrenia symptoms; for example, dysregulation of the dopaminergic system is associated with the positive symptoms and disrupted interactions between the GABAergic and glutamatergic systems are associated with the negative and cognitive symptoms (Shorter & Miller 2015).…”

“…Schizophrenia is a severe psychiatric disorder that is often characterized by positive symptoms, such as hallucinations, psychosis and mania, as well as negative symptoms, including anhedonia and social withdrawal (Shorter & Miller 2015). Several neurotransmitters may contribute to schizophrenia symptoms; for example, dysregulation of the dopaminergic system is associated with the positive symptoms and disrupted interactions between the GABAergic and glutamatergic systems are associated with the negative and cognitive symptoms (Shorter & Miller 2015).…”

Animal models of gene–environment interaction in schizophrenia: A dimensional perspective

“…Although DNA methylation and histone modifications comprise the major processes of epigenetic modifications, a growing variety of noncoding RNAs are also being increasingly recognized as another important epigenetic mechanism regulating gene transcription (Hannon, 2002; Chitwood et al, 2010; Dethoff et al, 2012). Similar to the early days of psychiatric genetics, most recent epigenetic studies have evaluated epigenetic abnormalities in so-called candidate genes, focusing on genes involved in synaptic neurotransmission, oxidative stress, inflammatory pathways or myelination (Svrakic et al, 2013; Pishva et al, 2014; Shorter et al, 2015). These studies are being followed by methylome-wide association analysis (MWAS) in patients with psychotic disorders.…”