title: The potential use of histone deacetylase inhibitors in the treatment of depression.
abstract: Numerous preclinical studies demonstrate that changes in gene expression in the brain occur in animal models of depression using exposure to stress, such as social defeat and leaned helplessness, and that repeated administration of antidepressants ameliorates these stress-induced changes in gene expression. These findings suggest that alteration in gene transcription in the central nervous system in response to stress plays an important role in the pathophysiology of depression. Recent advances in epigenetics have led to the realization that chromatin remodeling mediated by histone deacetylase (HDAC) is closely involved in the regulation of gene transcription. In this context, we first review several preclinical studies demonstrating the antidepressant-like efficacy of HDAC inhibitors. We then suggest the efficacy of HDAC inhibitors in treatment-resistant depression based on the mechanism of action of HDAC. Finally, we discuss the possibility of using HDAC inhibitors in patients with treatment-resistant depression.
authors.affiliation: Department of Psychiatry and Neurosciences, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Fuchikami
authors.affiliation: Department of Psychiatry and Neurosciences, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, Japan.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Department of Neuropsychiatry, Kochi Medical School, Kochi University, Kohasu Oko-cho, Nankoku, Kochi 783-8505, Japan. Electronic address: smorinob@kochi-u.ac.jp.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Morinobu
authors.affiliation: Department of Psychiatry and Neurosciences, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okada
authors.affiliation: Department of Cellular and Molecular Pharmacology, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Yamawaki
authors.affiliation: Department of Psychiatry and Neurosciences, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, Japan.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Yamawaki
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans
chemical_list: D000928:Antidepressive Agents; D056572:Histone Deacetylase Inhibitors
keywords: Antidepressant; Brain-derived neurotrophic factor (BDNF); Depression; Histone deacetylase; Histone deacetylase (HDAC) inhibitor