title: DNA methylation in schizophrenia: progress and challenges of epigenetic studies.
abstract: Schizophrenia is a severe psychiatric disease affecting about 1% of the world's population, with significant effects on patients and society. Genetic studies have identified several candidate risk genes or genomic regions for schizophrenia, and epidemiological studies have revealed several environmental risk factors. However, the etiology of schizophrenia still remains largely unknown. Epigenetic mechanisms such as DNA methylation and histone modifications can explain the interaction between genetic and environmental factors at the molecular level, and accumulating evidence suggests that such epigenetic alterations are involved in the pathophysiology of schizophrenia. However, replication studies to validate previous findings and investigations of the causality of epigenetic alterations in schizophrenia are needed. Here, we review epigenetic studies of schizophrenia patients using postmortem brains or peripheral tissues, focusing mainly on DNA methylation. We also highlight the recent progress and challenges in characterizing the potentially complex and dynamic patterns of epigenomic variations. Such studies are expected to contribute to our understanding of schizophrenia etiology and should provide novel opportunities for the development of therapeutic drugs.
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 1138655, Japan ; Department of Molecular Psychiatry, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 1138655, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Nishioka
authors.affiliation: Department of Molecular Psychiatry, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 1138655, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Bundo
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 1138655, Japan.
authors.forename: Kiyoto
authors.initials: K
authors.lastname: Kasai
authors.affiliation: Department of Molecular Psychiatry, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 1138655, Japan ; PRESTO, Japan Science and Technology Agency, 4-1-8, Honcho, Kawaguchi-shi, Saitama 332-0012, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Iwamoto