Laboratory of Clinical and Translational Studies, National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism, Poolesville, Maryland, USA.
Biol Psychiatry. 2010 Feb 15;67(4):323-30. doi: 10.1016/j.biopsych.2009.10.016. Epub 2009 Dec 16.
Genetic factors interact with environmental stressors to moderate risk for human psychopathology, but sex may also be an important mediating factor. Different strategies for coping with environmental stressors have evolved in males and females, and these differences may underlie the differential prevalence of certain types of psychopathology in the two sexes. In this study, we investigated the possibility of sex-specific gene-environment interactions in a nonhuman primate model of response to social threat.
Rhesus macaques (77 males and 106 females) were exposed to an unfamiliar conspecific. Using factor analysis, we identified three behavioral factors characterizing the response to social threat. Monkeys were genotyped for the serotonin transporter-linked polymorphism (5-HTTLPR), and the effects of genotype, early life stress, and sex on behavioral responses were evaluated.
Factor analysis produced five factors: High-Risk Aggression, Impulsivity/Novelty-Seeking, Gregariousness/Boldness, Harm Avoidance, and Redirected Aggression. Overall, males displayed higher levels of High-Risk Aggression and Gregariousness/Boldness than females. Levels of High-Risk Aggression in males carrying the s allele were significantly higher if they were also exposed to early adversity in the form of peer rearing.
Our findings support those from studies in humans suggesting that males are more vulnerable to externalizing or aggression-related disorders. The results highlight the importance of interactions that exist among behavior, genes, and the environment and suggest that sex differences in vulnerability to psychopathology may be grounded in our evolutionary history.
遗传因素与环境压力相互作用,调节人类精神病理学的风险,但性别也可能是一个重要的中介因素。男性和女性已经进化出了不同的应对环境压力的策略,这些差异可能是两种性别中某些类型精神病理学发病率不同的基础。在这项研究中,我们在一种非人类灵长类动物对社会威胁反应的模型中研究了性别特异性基因-环境相互作用的可能性。
恒河猴(77 只雄性和 106 只雌性)被暴露于一只陌生的同种动物。我们通过因子分析,确定了三个行为因素,这些因素可以描述对社会威胁的反应。猴子被进行了 5-羟色胺转运体基因(5-HTTLPR)的基因分型,评估了基因型、早期生活压力和性别的作用对行为反应的影响。
因子分析产生了五个因素:高风险攻击、冲动/寻求新奇、合群/大胆、回避伤害和转移攻击。总体而言,雄性比雌性表现出更高水平的高风险攻击和合群/大胆。如果携带 s 等位基因的雄性也经历了同伴养育形式的早期逆境,那么它们的高风险攻击水平会显著升高。
我们的发现支持了人类研究的结果,表明男性更容易受到外化或与攻击相关的疾病的影响。这些结果强调了行为、基因和环境之间存在相互作用的重要性,并表明对精神病理学易感性的性别差异可能根植于我们的进化历史。