Department of Pharmacology and Toxicology, Medical Faculty, Medical University, Sofia, Bulgaria.
J Pharm Pharmacol. 2012 Oct;64(10):1349-58. doi: 10.1111/j.2042-7158.2012.01475.x. Epub 2012 Apr 8.
Epigenetics refers to the heritable, but reversible regulation of various biological functions. Changes in DNA methylation and chromatin structure derived from histone modifications are involved in the brain development, pathogenesis and pharmacotherapy of brain disorders.
Evidence suggests that epigenetic modulations play key roles in psychiatric diseases such as schizophrenia and bipolar disorder. The analysis of epigenetic aberrations in the mechanisms of psychoactive drugs helps to determine dysfunctional genes and pathways in the brain, to predict side effects of drugs on human genome and identify new pharmaceutical targets for treatment of psychiatric diseases.
Although numerous studies have concentrated on epigenetics of psychosis, the epigenetic studies of antipsychotics are limited. Here we present epigenetic mechanisms of various psychoactive drugs and review the current literature on psychiatric epigenomics. Furthermore, we discuss various epigenetic modulations in the pharmacology and toxicology of typical and atypical antipsychotics, methionine, lithium and valproic acid.
表观遗传学是指各种生物功能的可遗传但可逆转的调控。源自组蛋白修饰的 DNA 甲基化和染色质结构的变化涉及脑发育、脑疾病的发病机制和药物治疗。
有证据表明，表观遗传调控在精神疾病（如精神分裂症和双相情感障碍）中起着关键作用。对精神活性药物作用机制中表观遗传异常的分析有助于确定大脑中功能失调的基因和途径，预测药物对人类基因组的副作用，并确定治疗精神疾病的新药物靶点。
尽管许多研究集中在精神分裂症的表观遗传学上，但抗精神病药物的表观遗传学研究有限。在这里，我们介绍了各种精神活性药物的表观遗传机制，并回顾了精神神经表观基因组学的现有文献。此外，我们还讨论了典型和非典型抗精神病药物、蛋氨酸、锂和丙戊酸在药理学和毒理学中的各种表观遗传调控。
