Prefrontal cortex lesions and MAO-A modulate aggression in penetrating traumatic brain injury
Prefrontal cortex lesions and MAO-A modulate aggression in penetrating traumatic brain injury
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DOI：
10.1212/wnl.0b013e318211c33e
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发表时间：
2011-03-01
期刊：
影响因子：
9.9
通讯作者：
Grafman, J.
中科院分区：
文献类型：
--
作者：
Pardini, M.;Krueger, F.;Grafman, J.
目的：探讨脑损伤部位与单胺氧化酶A(MAO-A)在穿透性脑损伤(PTBI)患者攻击行为发生中的相互作用。PTBI患者根据病变部位(前额叶皮质[PFC]与非PFC)进行分组，并进行MAO-A基因多态与低转录活性和高转录活性相关的基因分型。攻击行为采用神经精神病学问卷(NPI-a)中的攻击/激动子量表(NPI-a)进行评估。结果：攻击性程度最高的患者优先表现在PFC区域。MAO-A转录活性与攻击性损伤定位之间存在显著的交互作用。在对照组中，低活性等位基因携带者比高活性等位基因携带者表现出更高的攻击性。在PFC病变组中，2个MAO-A等位基因携带者之间攻击性无显著差异，而在非PFC病变组中，高活性等位基因携带者的攻击性高于低活性等位基因携带者。在对照组和非PFC损伤组中，NPI-a得分较高与更严重的儿童心理创伤经历和创伤后应激障碍症状有关，而在PFC损毁组中则不相关。结论：病变部位和MAO-A基因在PTBI的攻击行为中存在交互作用。重要的是，PFC的完整性对于通过遗传易感性和创伤经历调节攻击行为是必要的。潜在地，病变定位和MAO-A基因数据可以结合起来，开发风险分层算法和针对PTBI攻击的个体化治疗。神经病学(R)2011；76：1038-1045
Objective: This study investigates the interaction between brain lesion location and monoamine oxidase A (MAO-A) in the genesis of aggression in patients with penetrating traumatic brain injury (PTBI).Methods: We enrolled 155 patients with PTBI and 42 controls drawn from the Vietnam Head Injury Study registry. Patients with PTBI were divided according to lesion localization (prefrontal cortex [PFC] vs non-PFC) and were genotyped for the MAO-A polymorphism linked to low and high transcriptional activity. Aggression was assessed with the aggression/agitation subscale of the Neuropsychiatric Inventory (NPI-a).Results: Patients with the highest levels of aggression preferentially presented lesions in PFC territories. A significant interaction between MAO-A transcriptional activity and lesion localization on aggression was revealed. In the control group, carriers of the low-activity allele demonstrated higher aggression than high-activity allele carriers. In the PFC lesion group, no significant differences in aggression were observed between carriers of the 2 MAO-A alleles, whereas in the non-PFC lesion group higher aggression was observed in the high-activity allele than in the low-activity allele carriers. Higher NPI-a scores were linked to more severe childhood psychological traumatic experiences and posttraumatic stress disorder symptomatology in the control and non-PFC lesion groups but not in the PFC lesion group.Conclusions: Lesion location and MAO-A genotype interact in mediating aggression in PTBI. Importantly, PFC integrity is necessary for modulation of aggressive behaviors by genetic susceptibilities and traumatic experiences. Potentially, lesion localization and MAO-A genotype data could be combined to develop risk-stratification algorithms and individualized treatments for aggression in PTBI. Neurology (R) 2011;76:1038-1045