The potential use of histone deacetylase inhibitors in the treatment of depression

• Published in: Progress in neuro-psychopharmacology & biological psychiatry Vol. 64; pp. 320 - 324
• Main Authors: Fuchikami, Manabu, Yamamoto, Shigeto, Morinobu, Shigeru, Okada, Satoshi, Yamawaki, Yosuke, Yamawaki, Shigeto
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 04.01.2016
• Subjects: Animals; Antidepressant; Antidepressive Agents - pharmacology; Antidepressive Agents - therapeutic use; Brain-derived neurotrophic factor (BDNF); Depression; Depressive Disorder - drug therapy; Depressive Disorder - genetics; Depressive Disorder - metabolism; Gene Expression Regulation - drug effects; Histone deacetylase; Histone deacetylase (HDAC) inhibitor; Histone Deacetylase Inhibitors - pharmacology; Histone Deacetylase Inhibitors - therapeutic use; Humans; Antidepressant; SAHA; Histone deacetylase; Histone deacetylase (HDAC) inhibitor; BDNF; Brain-derived neurotrophic factor (BDNF); VPA; FST; Depression; SB; NAD; PTSD; SSRI; NAc; CREB; SNRI; GDNF; TST; VLO; HAT; FEGF; SIRT; HDAC
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2015.03.010

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.