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OPRM1(A118G)多态性对健康男性攻击行为的行为和神经相关性的影响。

The influence of the OPRM1 (A118G) polymorphism on behavioral and neural correlates of aggression in healthy males.

机构信息

Department of Psychiatry, Psychotherapy and Psychosomatics, Faculty of Medicine, RWTH Aachen University, 52074, Aachen, Germany.

Department of Psychiatry, Psychotherapy and Psychosomatics, Faculty of Medicine, RWTH Aachen University, 52074, Aachen, Germany; JARA Institute Brain Structure Function Relationship Institute for Neuroscience and Medicine (INM 10), Forschungszentrum Jülich, 52425 Jülich, Germany.

出版信息

Neuropharmacology. 2019 Sep 15;156:107467. doi: 10.1016/j.neuropharm.2018.12.014. Epub 2018 Dec 12.

Abstract

Current models of aggression suggest that in addition to personality traits and environmental factors, biological vulnerability associated with genetics substantially impacts aggressive behavior. In a functional imaging study, we investigated the influence of the single nucleotide polymorphism of the mu 1 subtype opioid receptor gene (OPRM1), implicated in sociability, on correlates of trait and state aggression to delineate the function of these influences in aggression. A key aim was further to differentiate different aspects of aggressive reactions - namely, the reaction to provocation and the decision to punish an opponent. 59 healthy males performed a modified Taylor Aggression Paradigm during functional magnetic resonance imaging. The implementation of the paradigm allowed for individual assessments of the decision to behave aggressively, the experience of provocation and the ramification of punishment for the participant or the opponent. The influence of variation in the OPRM1 gene was measured by the functional A118G polymorphism. G allele carriers showed lower levels of general aggression and self-reported physical aggression. Additionally, these participants exhibited increased activation in dorsolateral prefrontal, orbitofrontal, anterior cingulate and insular cortices when choosing higher punishments for the opponent. The OPRM1 polymorphism did not influence aggression in reaction to social provocation. Thus, we suggest that this genetic variant affects one's trait aggressiveness rather than actual behavioral reactivity to provocation. Investigating brain regions that are specifically linked to provocation yielded activation in cortico-limbic circuits which might mediate the evaluation of provocation and the experience of anger and thus shed light on neural processes underlying the risk for aggressive behavior. This article is part of the Special Issue entitled 'Current status of the neurobiology of aggression and impulsivity'.

摘要

目前的攻击模型表明,除了个性特征和环境因素外,与遗传相关的生物脆弱性也会极大地影响攻击行为。在一项功能成像研究中,我们研究了与社交能力相关的μ1 型阿片受体基因(OPRM1)单核苷酸多态性对特质和状态攻击性相关因素的影响,以阐明这些影响在攻击行为中的作用。一个关键目标是进一步区分攻击反应的不同方面——即对挑衅的反应和惩罚对手的决定。59 名健康男性在功能磁共振成像期间执行了改良的泰勒攻击范式。该范式的实施允许对行为攻击的决定、挑衅的体验以及对参与者或对手的惩罚的后果进行个体评估。OPRM1 基因的变异通过功能 A118G 多态性来衡量。G 等位基因携带者表现出较低的一般攻击性和自我报告的身体攻击性。此外,这些参与者在选择对对手进行更高的惩罚时,背外侧前额叶、眶额皮质、前扣带和岛叶皮质的激活增加。OPRM1 多态性不会影响对社会挑衅的攻击。因此,我们认为这种遗传变异会影响一个人的特质攻击性,而不是对挑衅的实际行为反应。对与挑衅特异性相关的大脑区域的研究表明,在皮质边缘回路中存在激活,这可能介导对挑衅的评估和愤怒的体验,从而为攻击行为的潜在神经过程提供了线索。本文是特刊“攻击性和冲动性的神经生物学现状”的一部分。

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