Epigenetic Research in Neuropsychiatric Disorders: the "Tissue Issue".
Epigenetic Research in Neuropsychiatric Disorders: the "Tissue Issue".
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DOI：
10.1007/s40473-016-0083-4
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发表时间：
2016-09
影响因子：
1.7
通讯作者：
Fallin MD
中科院分区：
文献类型：
--
作者：
Bakulski KM;Halladay A;Hu VW;Mill J;Fallin MD
有证据表明，神经精神障碍与表观遗传标记有关，表观遗传标记是疾病的生物标记物、暴露的生物标记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病学流行病学研究都有方法上的挑战和明显的优势。脑组织研究受到病例和对照样本量小、表型不完全、死后时间选择和细胞异质性的挑战，但使用与原发疾病相关的组织是关键。基于血液的研究可以获得更大的样本量和更多的复制机会，以及在发病前和治疗过程中进行纵向测量的可能性。然而，血液研究也受到细胞类型异质性的挑战，许多人质疑将外周组织用作脑生物标记物的有效性。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，但目标组织的确认仍然很重要。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。应该采用跨组织研究以及先进的流行病学方法来更有效地进行神经精神病学表观遗传学研究。
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.