Holz Nathalie, Boecker Regina, Buchmann Arlette F, Blomeyer Dorothea, Baumeister Sarah, Hohmann Sarah, Jennen-Steinmetz Christine, Wolf Isabella, Rietschel Marcella, Witt Stephanie H, Plichta Michael M, Meyer-Lindenberg Andreas, Schmidt Martin H, Esser Günter, Banaschewski Tobias, Brandeis Daniel, Laucht Manfred
Department of Child and Adolescent Psychiatry and Psychotherapy.
Department of Biostatistics.
Cereb Cortex. 2016 Mar;26(3):904-14. doi: 10.1093/cercor/bhu249. Epub 2014 Oct 19.
Converging evidence emphasizes the role of an interaction between monoamine oxidase A (MAOA) genotype, environmental adversity, and sex in the pathophysiology of aggression. The present study aimed to clarify the impact of this interaction on neural activity in aggression-related brain systems. Functional magnetic resonance imaging was performed in 125 healthy adults from a high-risk community sample followed since birth. DNA was genotyped for the MAOA-VNTR (variable number of tandem repeats). Exposure to childhood life stress (CLS) between the ages of 4 and 11 years was assessed using a standardized parent interview, aggression by the Youth/Young Adult Self-Report between the ages of 15 and 25 years, and the VIRA-R (Vragenlijst Instrumentele En Reactieve Agressie) at the age of 15 years. Significant interactions were obtained between MAOA genotype, CLS, and sex relating to amygdala, hippocampus, and anterior cingulate cortex (ACC) response, respectively. Activity in the amygdala and hippocampus during emotional face-matching increased with the level of CLS in male MAOA-L, while decreasing in male MAOA-H, with the reverse pattern present in females. Findings in the opposite direction in the ACC during a flanker NoGo task suggested that increased emotional activity coincided with decreased inhibitory control. Moreover, increasing amygdala activity was associated with higher Y(A)SR aggression in male MAOA-L and female MAOA-H carriers. Likewise, a significant association between amygdala activity and reactive aggression was detected in female MAOA-H carriers. The results point to a moderating role of sex in the MAOA× CLS interaction for intermediate phenotypes of emotional and inhibitory processing, suggesting a possible mechanism in conferring susceptibility to violence-related disorders.
越来越多的证据强调了单胺氧化酶A（MAOA）基因型、环境逆境和性别之间的相互作用在攻击行为病理生理学中的作用。本研究旨在阐明这种相互作用对与攻击行为相关的脑系统神经活动的影响。对125名自出生起就被跟踪的来自高危社区样本的健康成年人进行了功能磁共振成像。对MAOA可变数目串联重复序列（VNTR）进行基因分型。使用标准化的家长访谈评估4至11岁期间的童年生活压力（CLS），使用青少年/青年成人自我报告评估15至25岁之间的攻击行为，并在15岁时使用VIRA-R（工具性和反应性攻击问卷）进行评估。分别在杏仁核、海马体和前扣带回皮质（ACC）反应方面，MAOA基因型、CLS和性别之间获得了显著的相互作用。在情绪面孔匹配过程中，男性MAOA-L型个体杏仁核和海马体的活动随CLS水平的升高而增加，而男性MAOA-H型个体则降低，女性呈现相反的模式。在侧翼不执行任务期间，ACC出现了相反方向的结果，表明情绪活动增加与抑制控制能力下降同时出现。此外，男性MAOA-L型和女性MAOA-H型携带者杏仁核活动增加与更高的青年/青年成人自我报告攻击得分相关。同样，在女性MAOA-H型携带者中检测到杏仁核活动与反应性攻击之间存在显著关联。结果表明，性别在MAOA×CLS相互作用中对情绪和抑制加工的中间表型具有调节作用，提示了一种可能导致暴力相关障碍易感性的机制。
