Douglas Mental Health University Institute, Verdun, Quebec, Canada; Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia, USA.
Psychiatry Res. 2017 Oct;256:298-304. doi: 10.1016/j.psychres.2017.06.048. Epub 2017 Jun 20.
Maternal smoking during pregnancy is the most commonly cited risk factor for ADHD. While the causal relation between this factor and ADHD is debated, several lines of evidence suggest that it modulates the severity of ADHD, particularly through higher association with conduct disorder (CD). We hypothesized that maternal smoking during pregnancy may be associated with differential methylation in selected genes in children with ADHD. DNA extracted from peripheral blood was used to examine methylation between 25 children exposed, and 22 children not exposed to maternal smoking during pregnancy. Three genes (AHRR, CYP1A1, GFI1) were selected based on previous results observed in the general population. Regression analysis was conducted between methylation levels in these candidate genes and: (a) total number of ADHD and CD symptoms; (b) birth weight. Significant differences in methylation were observed in each of the candidate genes between children exposed and not exposed to maternal smoking during pregnancy. Methylation at the selected sites showed significant association with specific phenotypes. Significant correlations were observed between methylation within AHRR and number of CD symptoms; GFI1 and number of ADHD symptoms and GFI1 and birth weight. These initial results may have important clinical implications if confirmed in a larger independent sample.
母亲怀孕期间吸烟是 ADHD 最常被引用的风险因素。虽然这个因素与 ADHD 之间的因果关系存在争议，但有几条证据表明它会调节 ADHD 的严重程度，特别是通过与品行障碍（CD）的更高关联。我们假设母亲怀孕期间吸烟可能与 ADHD 儿童选定基因中的差异甲基化有关。从外周血中提取的 DNA 用于检查暴露于母亲怀孕期间吸烟的 25 名儿童和未暴露于母亲怀孕期间吸烟的 22 名儿童之间的甲基化。根据在普通人群中观察到的先前结果，选择了三个基因（AHRR、CYP1A1、GFI1）。在这些候选基因中，进行了回归分析，以研究甲基化水平与以下方面之间的关系：（a）ADHD 和 CD 症状的总数；（b）出生体重。在暴露于和未暴露于母亲怀孕期间吸烟的儿童中，每个候选基因中的甲基化水平都存在显著差异。选定部位的甲基化与特定表型有显著关联。在 AHRR 内的甲基化与 CD 症状的数量之间，GFI1 与 ADHD 症状的数量和 GFI1 与出生体重之间存在显著相关性。如果在更大的独立样本中得到证实，这些初步结果可能具有重要的临床意义。
