Tanenbaum Centre for Pharmacogenetics, Molecular Brain Science, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Laboratory for Molecular Pathology of Psychiatric Disorders, RIKEN Center for Brain Science, Wako, Japan.
Transl Psychiatry. 2024 Jun 11;14(1):252. doi: 10.1038/s41398-024-02870-7.
Excessive and persistent aggressiveness is the most common behavioral problem that leads to psychiatric referrals among children. While half of the variance in childhood aggression is attributed to genetic factors, the biological mechanism and the interplay between genes and environment that results in aggression remains elusive. The purpose of this systematic review is to provide an overview of studies examining the genetics of childhood aggression irrespective of psychiatric diagnosis. PubMed, PsycINFO, and MEDLINE databases were searched using predefined search terms for aggression, genes and the specific age group. From the 652 initially yielded studies, eighty-seven studies were systematically extracted for full-text review and for further quality assessment analyses. Findings show that (i) investigation of candidate genes, especially of MAOA (17 studies), DRD4 (13 studies), and COMT (12 studies) continue to dominate the field, although studies using other research designs and methods including genome-wide association and epigenetic studies are increasing, (ii) the published articles tend to be moderate in sizes, with variable methods of assessing aggressive behavior and inconsistent categorizations of tandem repeat variants, resulting in inconclusive findings of genetic main effects, gene-gene, and gene-environment interactions, (iii) the majority of studies are conducted on European, male-only or male-female mixed, participants. To our knowledge, this is the first study to systematically review the effects of genes on youth aggression. To understand the genetic underpinnings of childhood aggression, more research is required with larger, more diverse sample sets, consistent and reliable assessments and standardized definition of the aggression phenotypes. The search for the biological mechanisms underlying child aggression will also benefit from more varied research methods, including epigenetic studies, transcriptomic studies, gene system and genome-wide studies, longitudinal studies that track changes in risk/ameliorating factors and aggression-related outcomes, and studies examining causal mechanisms.
过度和持续的攻击性是导致儿童精神科转诊的最常见行为问题。虽然儿童攻击性的一半差异归因于遗传因素,但导致攻击性的生物学机制和基因与环境之间的相互作用仍然难以捉摸。本系统评价的目的是提供一个综述,研究儿童攻击性的遗传学,而不论其精神科诊断如何。使用预定义的搜索词在 PubMed、PsycINFO 和 MEDLINE 数据库中搜索攻击性、基因和特定年龄组的研究。从最初产生的 652 项研究中,有 87 项研究被系统地提取出来进行全文审查和进一步的质量评估分析。研究结果表明:(i) 对候选基因的研究,特别是 MAOA(17 项研究)、DRD4(13 项研究)和 COMT(12 项研究)的研究继续占据主导地位,尽管使用其他研究设计和方法的研究,包括全基因组关联和表观遗传学研究,正在增加,(ii) 已发表的文章倾向于中等规模,具有不同的攻击性行为评估方法和串联重复变异的不一致分类,导致遗传主效应、基因-基因和基因-环境相互作用的结论不一致,(iii) 大多数研究是在欧洲进行的,仅涉及男性或男女混合参与者。据我们所知,这是第一项系统地综述基因对青少年攻击性影响的研究。为了了解儿童攻击性的遗传基础,需要更多的研究,使用更大、更多样化的样本集,一致和可靠的评估以及攻击性表型的标准化定义。寻找儿童攻击性的生物学机制也将受益于更多不同的研究方法,包括表观遗传学研究、转录组学研究、基因系统和全基因组研究、追踪风险/缓解因素和与攻击性相关结果变化的纵向研究,以及研究因果机制。