Gorodetsky E, Bevilacqua L, Carli V, Sarchiapone M, Roy A, Goldman D, Enoch M-A
Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, NIH, Rockville, MD, USA.
Genes Brain Behav. 2014 Jul;13(6):543-9. doi: 10.1111/gbb.12140. Epub 2014 May 31.
Aggressive disorders are moderately heritable; therefore, identification of genetic influences is important. The X-linked MAOA gene, encoding the MAOA enzyme, has a functional 30 bp repeat polymorphism in the promoter region (MAOA-LPR) that has been shown to influence aggression. Childhood trauma is a known risk factor for numerous psychopathologies in adulthood including aggressive behaviors. We investigated the interactive effect of MAOA-LPR genotype and a history of childhood trauma in predicting aggressive behaviors in a prisoner population. A total of 692 male prisoners were genotyped for MAOA-LPR with genotypes grouped into high and low transcriptional activity. Participant evaluations included measures of aggression (Brown-Goodwin Lifetime History of Aggression, BGHA), hostility (Buss-Durkee Hostility Inventory), impulsivity (Barratt Impulsiveness Scale), violence directed toward self and others, and childhood trauma [Childhood Trauma Questionnaire (CTQ)]. MAOA-LPR interacted with CTQ physical neglect (PN), the most common (47%) form of childhood trauma in this sample, to predict BGHA aggression (P = 0.002). Within the group not exposed to PN, carriers of the MAOA-LPR high-activity variant were more aggressive: (tR = 2.47, P < 0.014). We observed a crossover effect in that the increase in aggression scores with PN was greater in low-activity individuals (tR = 5.55, P < 0.0001) than in high-activity individuals (tR = 4.18, P < 0.0001). These findings suggest that childhood trauma and the functional MAOA-LPR polymorphism may interact to specifically increase risk for over aggressive behavior but not impulsivity or hostility. The MAOA-LPR low-activity variant may be protective against the development of aggressive behavior under low stress conditions, at least in this prisoner population.
攻击性行为障碍具有中度遗传性;因此,识别基因影响很重要。编码单胺氧化酶A(MAOA)的X连锁MAOA基因在启动子区域存在一个功能性的30bp重复多态性(MAOA-LPR),已被证明会影响攻击性。童年创伤是成年后多种精神病理学(包括攻击性行为)的已知风险因素。我们研究了MAOA-LPR基因型与童年创伤史在预测囚犯群体攻击性行为方面的交互作用。对总共692名男性囚犯进行了MAOA-LPR基因分型,基因型分为高转录活性和低转录活性两组。参与者评估包括攻击性行为测量(布朗-古德温攻击性行为终生史量表,BGHA)、敌意(巴斯-杜克敌意量表)、冲动性(巴拉特冲动性量表)、针对自我和他人的暴力行为以及童年创伤[童年创伤问卷(CTQ)]。MAOA-LPR与CTQ身体忽视(PN)相互作用,PN是该样本中最常见(47%)的童年创伤形式,可预测BGHA攻击性行为(P = 0.002)。在未遭受PN的组中,MAOA-LPR高活性变体携带者更具攻击性:(tR = 2.47,P < 0.014)。我们观察到一种交叉效应,即低活性个体中PN导致的攻击性行为得分增加幅度(tR = 5.55,P < 0.0001)大于高活性个体(tR = 4.18,P < 0.0001)。这些发现表明,童年创伤和功能性MAOA-LPR多态性可能相互作用,特别增加过度攻击性行为的风险,但不增加冲动性或敌意。MAOA-LPR低活性变体可能在低压力条件下对攻击性行为的发展具有保护作用,至少在这个囚犯群体中是这样。