Epigenetics and first-episode psychosis: A systematic review

Background: Schizophrenia has a large disease burden globally. Early intervention in psychosis, and therefore a decreased duration of untreated psychosis, has a positive clinical impact. There are several recognized risk factors for psychosis, including trauma history and substance use. This systematic review examined the literature for studies related to epigenetic changes in first-episode psychosis, with the goal of identifying future research directions. Methods: A literature review was conducted from inception to October 3, 2021 using MedLine/PubMed, Web of Science, and PsycInfo searches with the keywords ("first-episode schizophrenia" OR "first-episode psychosis" OR "drug-naive schizophrenia" OR "drug-naive psychosis") AND (epigenetic OR methylation OR hydroxymethylation OR "histone modification" OR "miRNA") as well as a search of the bibliography of the identified papers. Results: Seventeen studies that examined various portions of the genome were included in this systematic review. There were two studies that showed hypomethylation at the LINE-1 portion of the genome and two that showed hypermethylation at LINE-1. Additionally, two studies showed hypomethylation specifically at the GRIN2B promoter (part of LINE-1). Conclusions: Although sample sizes were small, these studies provide evidence for epigenetic alterations in early psychosis. Further research in this area is warranted for more definitive epigenetic correlations.