Ptak Carolyn, Petronis Arturas
The Krembil Family Epigenetics Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Dialogues Clin Neurosci. 2010;12(1):25-35. doi: 10.31887/DCNS.2010.12.1/cptak.
Psychiatric diseases place a tremendous burden on affected individuals, their caregivers, and the health care system. Although evidence exists for a strong inherited component to many of these conditions, dedicated efforts to identify DNA sequence-based causes have not been exceptionally productive, and very few pharmacologic treatment options are clinically available. Many features of psychiatric diseases are consistent with an epigenetic dysregulation, such as discordance of monozygotic twins, late age of onset, parent-of-origin and sex effects, and fluctuating disease course. In recent years, experimental technologies have significantly advanced, permitting in-depth studies of the epigenome and its role in maintenance of normal genomic functions, as well as disease etiopathogenesis. Here, we present an epigenetic explanation for many characteristics of psychiatric disease, review the current literature on the epigenetic mechanisms involved in major psychosis, Alzheimer's disease, and autism spectrum disorders, and describe some future directions in the field of psychiatric epigenomics.
精神疾病给患者本人、其照料者以及医疗保健系统带来了巨大负担。尽管有证据表明许多此类疾病存在很强的遗传因素,但致力于确定基于DNA序列的病因的专门研究成果并不显著,临床上可用的药物治疗选择也非常少。精神疾病的许多特征与表观遗传失调相一致,例如同卵双胞胎的不一致性、发病年龄较晚、亲本来源和性别效应以及病情波动。近年来,实验技术有了显著进步,使得对表观基因组及其在维持正常基因组功能以及疾病病因发病机制中的作用进行深入研究成为可能。在此,我们对精神疾病的许多特征提出一种表观遗传学解释,回顾有关主要精神病、阿尔茨海默病和自闭症谱系障碍所涉及的表观遗传机制的现有文献,并描述精神疾病表观基因组学领域的一些未来方向。