Bakulski Kelly M, Halladay Alycia, Hu Valerie W, Mill Jonathan, Fallin M Daniele
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.
Autism Science Foundation, New York City, New York, USA; Department of Pharmacology and Toxicology, Rutgers University, New Brunswick, New Jersey, USA.
Curr Behav Neurosci Rep. 2016 Sep;3(3):264-274. doi: 10.1007/s40473-016-0083-4. Epub 2016 Aug 2.
Evidence has linked neuropsychiatric disorders with epigenetic marks as either a biomarker of disease, biomarker of exposure, or mechanism of disease processes. Neuropsychiatric epidemiologic studies using either target brain tissue or surrogate blood tissue each have methodological challenges and distinct advantages.
Brain tissue studies are challenged by small sample sizes of cases and controls, incomplete phenotyping, post-mortem timing, and cellular heterogeneity, but the use of a primary disease relevant tissue is critical. Blood-based studies have access to much larger sample sizes and more replication opportunities, as well as the potential for longitudinal measurements, both prior to onset and during the course of treatments. Yet, blood studies also are challenged by cell-type heterogeneity, and many question the validity of using peripheral tissues as a brain biomarker. Emerging evidence suggests that these limitations to blood-based epigenetic studies are surmountable, but confirmation in target tissue remains important.
Epigenetic mechanisms have the potential to help elucidate biology connecting experiential risk factors with neuropsychiatric disease manifestation. Cross-tissue studies as well as advanced epidemiologic methods should be employed to more effectively conduct neuropsychiatric epigenetic research.
有证据表明神经精神疾病与表观遗传标记有关，表观遗传标记可作为疾病的生物标志物、暴露的生物标志物或疾病过程的机制。使用目标脑组织或替代血液组织的神经精神流行病学研究各有其方法学挑战和独特优势。
脑组织研究面临病例和对照样本量小、表型分型不完整、死后时间以及细胞异质性等挑战，但使用与疾病相关的原发性组织至关重要。基于血液的研究能够获取更大的样本量和更多的重复机会，以及在发病前和治疗过程中进行纵向测量的潜力。然而，血液研究也受到细胞类型异质性的挑战，许多人质疑使用外周组织作为脑生物标志物的有效性。新出现的证据表明，基于血液的表观遗传学研究的这些局限性是可以克服的，但在目标组织中进行验证仍然很重要。
表观遗传机制有可能帮助阐明将经验性风险因素与神经精神疾病表现联系起来的生物学机制。应采用跨组织研究以及先进的流行病学方法，以更有效地开展神经精神表观遗传学研究。
