Thaler Lea, Gauvin Lise, Joober Ridha, Groleau Patricia, de Guzman Rosherrie, Ambalavanan Amirthagowri, Israel Mimi, Wilson Samantha, Steiger Howard
Eating Disorders Program, Douglas University Institute, Montreal, Quebec, Canada; Psychiatry Department, McGill University, Montreal, Quebec, Canada; Research Centre, Douglas University Institute, Montreal, Quebec, Canada.
Research Centre, Centre Hospitalier de l'Université de Montréal, Monteal, Quebec, Canada; Department of Social & Preventive Medicine, School of Public Health, Université de Montréal, Montréal, Québec, Canada.
Prog Neuropsychopharmacol Biol Psychiatry. 2014 Oct 3;54:43-9. doi: 10.1016/j.pnpbp.2014.04.010. Epub 2014 May 5.
DNA methylation allows for the environmental regulation of gene expression and is believed to link environmental stressors to such mental-illness phenotypes as eating disorders. Numerous studies have shown an association between bulimia nervosa (BN) and variations in brain-derived neurotrophic factor (BDNF). BDNF has also been linked to borderline personality disorder (BPD) and to such traits as reward dependence. We examined the extent to which BDNF methylation corresponded to bulimic or normal-eater status, and also to the presence of comorbid borderline personality disorder (BPD) and childhood abuse. Our sample consisted of 64 women with BN and 32 normal-eater (NE) control women. Participants were assessed for eating-disorder symptoms, comorbid psychopathology, and childhood trauma, and then they were required to provide blood samples for methylation analyses. We observed a significant site×group (BN vs. NE) interaction indicating that women with BN showed increases in methylation at specific regions of the BDNF promoter. Furthermore, examining effects of childhood abuse and BPD, we observed significant site×group interactions such that groups composed of individuals with childhood abuse or BPD had particularly high levels of methylation at selected CpG sites. Our findings suggest that BN, especially when co-occurring with childhood abuse or BPD, is associated with a propensity towards elevated methylation at specific BDNF promoter region sites. These findings imply that hypermethylation of the BDNF gene may be related to eating disorder status, developmental stress exposure, and comorbid psychopathology.
DNA甲基化允许对基因表达进行环境调控，并被认为将环境应激源与诸如饮食失调等精神疾病表型联系起来。大量研究表明神经性贪食症（BN）与脑源性神经营养因子（BDNF）的变异之间存在关联。BDNF还与边缘型人格障碍（BPD）以及诸如奖励依赖等特质有关。我们研究了BDNF甲基化在多大程度上与贪食或正常饮食状态相对应，以及与共病边缘型人格障碍（BPD）和童年期虐待的存在情况相对应。我们的样本包括64名患有BN的女性和32名正常饮食（NE）的对照女性。对参与者进行饮食失调症状、共病精神病理学和童年创伤的评估，然后要求她们提供血液样本进行甲基化分析。我们观察到一个显著的位点×组（BN与NE）交互作用，表明患有BN的女性在BDNF启动子的特定区域甲基化增加。此外，在研究童年期虐待和BPD的影响时，我们观察到显著的位点×组交互作用，使得由童年期虐待或BPD个体组成的组在选定的CpG位点具有特别高的甲基化水平。我们的研究结果表明，BN，尤其是与童年期虐待或BPD同时出现时，与特定BDNF启动子区域位点甲基化升高的倾向有关。这些发现意味着BDNF基因的高甲基化可能与饮食失调状态、发育性应激暴露和共病精神病理学有关。
