Genotype Link With Extreme Antisocial Behavior The Contribution of Cognitive Pathways
Genotype Link With Extreme Antisocial Behavior The Contribution of Cognitive Pathways
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DOI：
10.1001/archgenpsychiatry.2010.163
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发表时间：
2010-12-01
影响因子：
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通讯作者：
Thapar, Anita
中科院分区：
文献类型：
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作者：
Langley, Kate;Heron, Jon;Thapar, Anita
内容：随着与常见疾病相关的基因越来越多地被发现，我们需要从观察关联到识别风险途径。高活性COMT基因型，在注意力缺陷/多动障碍（ADHD）的存在下，先前已被证明与极端的反社会行为有关。同样的基因型也影响了健康个体的认知功能。目的：复制COMT基因型与ADHD患者反社会行为之间的相关性，然后检测（1）执行控制受损或（2）社会理解受损是否作为该相关性的中间表型，并在COMT基因型与反社会行为之间的风险通路上。设计：前瞻性流行病学队列样本。设置：雅芳父母和儿童纵向研究。参与者：4365名儿童，其COMT瓦尔（158）Met基因型、ADHD症状和诊断以及社会认知/理解和执行控制的测量数据。主要结果测量：结果：我们重复了高活性COMT基因型与ADHD患者极端反社会行为的相关性（比值比，2.82; 95%可信区间，2.02-3.94; P
Context: As genes associated with common disorders are increasingly identified, we need to progress from observing associations to identifying risk pathways. The high-activity COMT genotype, in the presence of attention-deficit/hyperactivity disorder (ADHD), has previously been shown to be associated with extreme antisocial behavior. The same genotype has also been implicated in affecting cognitive function in healthy individuals. Impaired cognitive function might therefore lie on the risk pathway from genotype to clinical outcome.Objectives: To replicate the association between COMT genotype and antisocial behavior in ADHD and to then test whether (1) impaired executive control or (2) impaired social understanding act as intermediate phenotypes for this association and lie on the risk pathway between COMT genotype and antisocial behavior.Design: Prospective epidemiological cohort sample.Setting: The Avon Longitudinal Study of Parents and Children.Participants: Four thousand three hundred sixty-five children with data on COMT Val(158)Met genotype, ADHD symptoms and diagnoses, and measures of social cognition/understanding and executive control.Main Outcome Measures: Antisocial behavior at age 7.5 years assessed using DSM-IV conduct disorder symptoms.Results: We replicated the association of the high-activity COMT genotype, in the presence of ADHD, with extreme antisocial behavior (odds ratio, 2.82; 95% confidence interval, 2.02-3.94; P