Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Maastricht University Medical Centre, European Graduate School of Neuroscience, South Limburg Mental Health Research and Teaching Network, Vijverdalseweg 1, Maastricht 6226 NB, The Netherlands.
Schizophr Bull. 2009 Nov;35(6):1045-56. doi: 10.1093/schbul/sbp104. Epub 2009 Sep 25.
The major psychotic disorders schizophrenia and bipolar disorder are etiologically complex involving both heritable and nonheritable factors. The absence of consistently replicated major genetic effects, together with evidence for lasting changes in gene expression after environmental exposures, is consistent with the concept that the biologic underpinnings of these disorders are epigenetic in form rather than DNA sequence based. Psychosis-associated environmental exposures, particularly at key developmental stages, may result in long-lasting epigenetic alterations that impact on the neurobiological processes involved in pathology. Although direct evidence for epigenetic dysfunction in both schizophrenia and bipolar disorder is still limited, methodological technologies in epigenomic profiling have advanced. This means that we are at the exciting stage where it is feasible to start investigating molecular modifications to DNA and histones and examine the mechanisms by which environmental factors can act upon the genome to bring about epigenetic changes in gene expression involved in the etiology of these disorders. Given the dynamic nature of the epigenetic machinery and potential reversibility of epigenetic modifications, the understanding of such mechanisms is of key relevance for clinical psychiatry and for identifying new targets for prevention and/or intervention.
主要的精神病障碍，如精神分裂症和双相情感障碍，其病因复杂，涉及遗传和非遗传因素。一致复制的主要遗传效应的缺失，以及环境暴露后基因表达持续变化的证据，与这些障碍的生物学基础是表观遗传形式而不是基于 DNA 序列的概念是一致的。与精神病相关的环境暴露，特别是在关键的发育阶段，可能导致持久的表观遗传改变，从而影响涉及病理学的神经生物学过程。尽管在精神分裂症和双相情感障碍中直接证据仍然有限，但在表观基因组图谱的方法学技术上已经取得了进展。这意味着我们正处在一个令人兴奋的阶段，即可以开始研究 DNA 和组蛋白的分子修饰，并研究环境因素如何作用于基因组，从而导致这些疾病病因中涉及的基因表达的表观遗传变化。鉴于表观遗传机制的动态性质和表观遗传修饰的潜在可逆性，对这些机制的理解对临床精神病学和识别预防和/或干预的新靶点具有关键意义。
