Xu Yi, Chen Xiang-Tao, Luo Man, Tang Yuqing, Zhang Guangxiang, Wu De, Yang Bin, Ruan Di-Yun, Wang Hui-Li
School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, Anhui Province, 230009, PR China.
School of Pharmacy, Anhui Medical University, Hefei, Anhui Province, 230031, PR China.
J Psychiatr Res. 2015 May;64:40-50. doi: 10.1016/j.jpsychires.2015.03.006. Epub 2015 Mar 22.
Attention deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders of childhood. Despite its prevalence, the critical factors involved in its development remain to be identified. It was recently suggested that epigenetic mechanisms probably contribute to the etiology of ADHD. The present study was designed to examine the associations of epigenetic markers with ADHD among Chinese Han children, aiming to establish the prediction model for this syndrome from the epigenetic perspective. We conducted a pair-matching case-control study, and the ADHD children were systematically evaluated via structured diagnostic interviews, including caregiver interviews, based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, revised criteria (DSM-IV-R). The expression levels of risk genes DAT1, DRD4, DRD5, as well as their promoter methylation, were determined respectively, followed by the expression profiles of histone-modifying genes p300, MYST4, HDAC1, MeCP2. The multivariate logistic regressions were performed to establish ADHD prediction models. All of the seven genes tested were identified as risk factors for ADHD. The methylation of one critical CpG site located upstream of DRD4 was shown to affect its transcription, suggesting a role in ADHD's development. Aberrant DNA methylation and histone acetylation were indicated in ADHD patients. In addition, a prediction model was established using the combination of p300, MYST4 and HDAC1, with the accuracy of 0.9338. This is, to our knowledge, the first study to clearly demonstrate the associations between epigenetic markers and ADHD, shedding light on the preliminary diagnosis and etiological studies of this widespread disorder.
注意缺陷多动障碍（ADHD）是儿童期最常见的精神障碍之一。尽管其发病率很高，但其发展过程中涉及的关键因素仍有待确定。最近有人提出，表观遗传机制可能在ADHD的病因中起作用。本研究旨在探讨中国汉族儿童表观遗传标记与ADHD之间的关联，旨在从表观遗传学角度建立该综合征的预测模型。我们进行了一项配对病例对照研究，并根据《精神疾病诊断与统计手册》第4版修订标准（DSM-IV-R），通过结构化诊断访谈（包括照顾者访谈）对ADHD儿童进行了系统评估。分别测定了风险基因DAT1、DRD4、DRD5的表达水平及其启动子甲基化水平，随后测定了组蛋白修饰基因p300、MYST4、HDAC1、MeCP2的表达谱。进行多因素逻辑回归以建立ADHD预测模型。所检测的7个基因均被确定为ADHD的危险因素。位于DRD4上游的一个关键CpG位点的甲基化被证明会影响其转录，提示其在ADHD发展中的作用。ADHD患者存在异常的DNA甲基化和组蛋白乙酰化。此外，利用p300、MYST4和HDAC1建立了预测模型，准确率为0.9338。据我们所知，这是第一项明确证明表观遗传标记与ADHD之间关联的研究，为这种广泛疾病的初步诊断和病因学研究提供了线索。
