Epigenetic mechanisms in schizophrenia and other psychotic disorders: a systematic review of empirical human findings.

Publication date: Jan 06, 2020

Schizophrenia and other psychotic disorders are highly debilitating psychiatric conditions that lack a clear etiology and exhibit polygenic inheritance underlain by pleiotropic genes. The prevailing explanation points to the interplay between predisposing genes and environmental exposure. Accumulated evidence suggests that epigenetic regulation of the genome may mediate dynamic gene-environment interactions at the molecular level by modulating the expression of psychiatric phenotypes through transcription factors. This systematic review summarizes the current knowledge linking schizophrenia and other psychotic disorders to epigenetics, based on PubMed and Web of Science database searches conducted according to the PRISMA guidelines. Three groups of mechanisms in case-control studies of human tissue (i.e., postmortem brain and bio-fluids) were considered: DNA methylation, histone modifications, and non-coding miRNAs. From the initial pool of 3,204 records, 152 studies met our inclusion criteria (11,815/11,528, 233/219, and 2,091/1,827 cases/controls for each group, respectively). Many of the findings revealed associations with epigenetic modulations of genes regulating neurotransmission, neurodevelopment, and immune function, as well as differential miRNA expression (e.g., upregulated miR-34a, miR-7, and miR-181b). Overall, actual evidence moderately supports an association between epigenetics and schizophrenia and other psychotic disorders. However, heterogeneous results and cross-tissue extrapolations call for future work. Integrating epigenetics into systems biology may critically enhance research on psychosis and thus our understanding of the disorder. This may have implications for psychiatry in risk stratification, early recognition, diagnostics, precision medicine, and other interventional approaches targeting epigenetic fingerprints.

Smigielski, L., , Jagannath, R”ossler, W., Walitza, S., and Gr”unblatt, E. Epigenetic mechanisms in schizophrenia and other psychotic disorders: a systematic review of empirical human findings. 06126. 2020 Mol Psychiatry.

Concepts Keywords
Brain Epigenetics systems
Cross Psychotic disorders
Differential Psychosis understanding disorder
Epigenetic Branches of biology
Epigenetics Psychiatry
Etiology Psychopathology
Gene Gene expression
Genome RNA
Histone DNA
Immune Function Epigenetics
Interplay MicroRNA
Methylation Psychosis
MiRNA Schizophrenia
Modulations
Neurodevelopment
Neurotransmission
Phenotypes
Pleiotropic
Polygenic Inheritance
Postmortem
Precision Medicine
Psychiatry
Psychosis
Psychotic Disorders
PubMed
Schizophrenia
Stratification
Transcription Factors

Semantics

Type Source Name
disease MESH schizophrenia
disease MESH psychotic disorders
pathway REACTOME DNA methylation
drug DRUGBANK Methionine

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