反社会行为的遗传基础:基因多态性和DNA甲基化

反社会行为是受遗传与环境共同影响的不良行为。分子遗传学和神经生物学的研究发现,基因以基因多态性和DNA甲基化的方式影响脑结构、功能及脑内神经递质的产生和释放,进而影响反社会行为的发生发展。本文从基因多态性和DNA甲基化两方面整理了5-HTT、MAOA、OXTR等8个候选基因与反社会行为的关联。并提出未来研究需进一步探讨基因、脑和神经递质对反社会行为的联合作用。同时,扩展多基因位点、基因多态性与DNA甲基化、积极环境与基因交互作用对反社会行为影响的研究,以全面探索反社会行为发生的遗传基础,进而更加有效的预防反社会行为。     

反社会行为的遗传基础:基因多态性和DNA甲基化

反社会行为是受遗传与环境共同影响的不良行为。分子遗传学和神经生物学的研究发现,基因以基因多态性和DNA甲基化的方式影响脑结构、功能及脑内神经递质的产生和释放,进而影响反社会行为的发生发展。本文从基因多态性和DNA甲基化两方面整理了5-HTT、MAOA、OXTR等8个候选基因与反社会行为的关联。并提出未来研究需进一步探讨基因、脑和神经递质对反社会行为的联合作用。同时,扩展多基因位点、基因多态性与DNA甲基化、积极环境与基因交互作用对反社会行为影响的研究,以全面探索反社会行为发生的遗传基础,进而更加有效的预防反社会行为。     

多巴胺、5-羟色胺通路相关基因及家庭环境对创造力的影响及其作用机制

创造力的遗传基础是近年来创造力研究领域的前沿和热点问题, 但仍尚处于起步阶段, 也未有研究系统探讨遗传与环境因素的交互作用对创造力的影响及其作用机制。本课题拟在中国汉族人群中考察多巴胺(DA)、5-羟色胺(5-HT)神经递质通路上的32个基因约700个多态性位点与创造力的关系, 并首次探讨家庭环境在遗传多态性与创造力关系中的调节作用。研究内容包括：(1)通过单基因、基于通路以及基因—基因交互作用的关联分析, 考察遗传多态性对创造力的影响, 揭示创造力的遗传基础; (2)通过基因—环境交互作用的关联分析, 考察家庭环境在遗传与创造力关系中的调节作用; (3)通过结构方程模型的比较分析, 揭示遗传与家庭环境在创造力两个方面(创造思维与创造人格)共享的与特异的作用机制。该项目成果能够从遗传与环境交互作用的角度阐明创造力个体差异的原因, 有助于构建基于创造力个体差异分析的理论模型, 对创造人才的鉴别和培养具有重要现实意义。     

多巴胺相关基因甲基化、家庭环境与创造力的关系

“遗传与环境”的争论一直是创造力研究的核心问题, 但目前对于环境以及遗传与环境交互作用对创造力影响的分子生物机制还未有研究涉及。近年来, 随着表观遗传学的兴起, 揭示影响心理行为的表观遗传机制现已成为心理学研究的热点。作为环境与基因组之间的纽带, 表观遗传学研究为揭示环境以及遗传与环境交互作用对创造力影响的分子生物机制提供了机遇。本研究以多巴胺相关基因、家庭环境以及两者对于创造力的交互作用为切入点, 对影响创造力的表观遗传机制进行考察, 并在此基础之上, 对环境以及遗传与环境交互作用对创造力影响的分子生物机制进行探索。具体研究内容包括：(1)通过对多巴胺相关基因甲基化模式与创造力关系的系统考察, 筛选出甲基化模式与创造力有关的基因; (2)对筛选出的基因, 进一步考察其甲基化模式在家庭环境及其遗传多态性与家庭环境交互作用对创造力影响中的中介作用。本研究有助于揭示创造力的表观遗传机制, 深化关于遗传与环境对创造力影响的作用机制的理解。     

发展性阅读障碍的遗传关联分析

发展性阅读障碍是一种遗传性很高的认知功能缺陷, 运用关联分析对其遗传机制进行研究是近年来的新趋势。从研究方法的视角可以将现有的关联分析研究归为以下三类：家系法研究、病例-控制法研究和数量性状关联分析研究。阅读障碍关联分析研究的新趋势主要体现在与全基因组扫描技术、神经成像技术以及基因功能研究的结合上, 促进了从“基因-大脑-行为”层面对发展性阅读障碍的遗传机制进行理解。     

多动症的遗传学研究概述

多动症多始于儿童期,并能持续至成年期。传统的家庭、双生子和养子女研究表明,多动症是受遗传影响的。双生子研究现在被用来定义多动症表型,分析性别差异,测试基因对持续性和共病的影响,以及研究遗传与环境的互动。多动症的分子遗传学研究集中在功能候选基因的关联分析上。多动症与DRD4和DRD5的关系比较一致。最新的研究也显示COMT的影响。关联分析（linkage analysis）显示这些单个基因的影响都不大。这个领域还有待于大规模的“全基因关联”分析。至今为止的证据显示,研究基因-表型关联以及基因与环境互动对多动症的影响将日趋重要     

MAOA基因与环境对反社会行为的交互作用及其可能的脑机制

反社会行为具有重要的遗传学基础。MAOA基因是反社会行为的重要候选基因,该基因与环境对反社会行为具有交互作用,然而其内在作用机制尚不清楚。与情绪管理相关的脑区和神经回路,以及与工作记忆能力相关的脑区和神经回路在其中起重要作用。未来研究可从多基因-环境交互作用、理论模型验证、脑结构与功能的中介作用等方面进一步深化MAOA基因与反社会行为的关系研究。     

COMT基因rs6267多态性与母亲教养行为对青少年身体攻击和关系攻击的交互作用

遗传与环境如何交互作用影响儿童青少年的攻击行为是当前攻击研究中的重要前沿课题之一。近年来, 分子遗传学关于人类攻击的研究已拓展到对不同攻击亚类(身体攻击和关系攻击)的遗传基础的探讨。本研究运用问卷法与DNA分型技术, 对1258名儿童进行为时4年(四年级—七年级)的追踪调查, 考察COMT基因rs6267多态性与母亲教养行为对青少年身体攻击和关系攻击的交互作用以及性别在其中的调节作用。结果发现, COMT基因rs6267多态性与母亲教养行为仅交互作用于男青少年的身体攻击, 母亲教养行为显著预测GG 基因型男青少年的身体攻击, 但对T等位基因男青少年身体攻击的预测作用并不显著。COMT基因rs6267多态性与母亲教养行为对青少年关系攻击的交互作用不显著。本研究结果表明, 身体攻击和关系攻击具有不同遗传基础和发生机制。     

发展行为遗传学简介

发展行为遗传学是发展心理学与行为遗传学的交叉学科, 旨在探明遗传与环境对人类心理与行为发展是否存在影响, 如何产生影响, 以及该影响及其作用机制是否随年龄增长而发展变化的问题。该学科与行为遗传学在研究对象、设计和内容等方面存在不同; 开展发展行为遗传学研究需要综合运用心理测量法和行为遗传学研究方法; 未来研究应拓宽和深化候选基因与行为关联性的考察, 并着力探析基因与环境的相互作用机制。     

儿童对立违抗性障碍研究的进展及启示

随着基因技术及生物工程技术的迅速发展,人们逐渐发现与冲动行为相关基因的存在,研究认为DA、5-HT、MAO等基因多态性与冲动行为有关,从而进一步认识到ODD与遗传因素有关且属于多基因遗传.对儿童对立违抗性障碍(ODD)的生物学机制及社会心理应激因素进行了系统的分析,对进一步探讨ODD的发病机制有所启示.     

COMT基因多态性与攻击行为的关系

攻击行为的发生具有重要的遗传学基础。近年来, 随着分子遗传学的发展, 对攻击行为发生机制的研究已经深入到分子水平, COMT基因成为攻击行为遗传学研究的候选基因之一, 然而以人类为被试的研究结论尚存在分歧, 甚至相互矛盾。通过回顾、梳理既有关于COMT基因多态性与个体攻击行为关系的研究, 剖析了研究结论尚存在分歧和矛盾的原因, 并在此基础上从SNP标记、被试群体、研究设计、神经生物机制等几个方面展望了未来研究的方向。     

Sex differences in the genetic and environmental influences on childhood conduct disorder and adult antisocial behavior

Sex differences in the genetic and environmental influences on childhood conduct disorder and adult antisocial behavior were examined in a large community sample of 6,383 adult male, female, and opposite-sex twins. Retrospective reports of childhood conduct disorder (prior to 18 years of age) were obtained when participants were approximately 30 years old, and lifetime reports of adult antisocial behavior (antisocial behavior after 17 years of age) were obtained 8 years later. Results revealed that either the genetic or the shared environmental factors influencing childhood conduct disorder differed for males and females (i.e., a qualitative sex difference), but by adulthood, these sex-specific influences on antisocial behavior were no longer apparent. Further, genetic and environmental influences accounted for proportionally the same amount of variance in antisocial behavior for males and females in childhood and adulthood (i.e., there were no quantitative sex differences). Additionally, the stability of antisocial behavior from childhood to adulthood was slightly greater for males than females. Though familial factors accounted for more of the stability of antisocial behavior for males than females, genetic factors accounted for the majority of the covariation between childhood conduct disorder and adult antisocial behavior for both sexes. The genetic influences on adult antisocial behavior overlapped completely with the genetic influences on childhood conduct disorder for both males and females. Implications for future twin and molecular genetic studies are discussed.     

Impulsivity, aggression, and serotonin: a molecular psychobiological perspective

The expression of aggressiveness, which constitutes many facets of behavior, is influenced by a complex interaction of biologic, psychologic, and social variables. Even though individual differences in impulsivity and the behavioral consequences, such as aggression, addiction, and suicidality, are substantially heritable, they ultimately result from an interplay between genetic variations and environmental factors. While formation and integration of multiple neural networks is dependent on the actions of neurotransmitters, such as serotonin (5HT), converging lines of evidence indicate that genetically determined variability in serotonergic gene expression influences complex traits including that of inappropriately aggressive behavior. This contribution reviews studies of major gene effects in inbred and knockout strains of mice with increased aggression-related behavior and discusses the relevance of several serotonergic gene variations in humans which include high aggressiveness as part of the phenotype. Although special emphasis is given to the molecular psychobiology of 5HT in aggression-related behavior in rodents, nonhuman primates, and humans, relevant conceptual and methodological issues in the search for candidate genes for impulsivity and aggressiveness and for the development of mouse models of aggressive and antisocial behavior in humans are also considered.     

Deviant Peer Affiliation and Antisocial Behavior: Interaction with Monoamine Oxidase A (MAOA) Genotype

Although genetic and environmental factors are separately implicated in the development of antisocial behavior (ASB), interactive models have emerged relatively recently, particularly those incorporating molecular genetic data. Using a large sample of male Caucasian adolescents and young adults from the National Longitudinal Study of Adolescent Health (Add Health), the association of deviant peer affiliation, the 30-base pair variable number tandem repeat polymorphism in promoter region of the monoamine oxidase-A (MAOA) gene, and their interaction, with antisocial behavior (ASB) was investigated. Weighted analyses accounting for over-sampling and clustering within schools as well as controlling for age and wave suggested that deviant peer affiliation and MAOA genotype were each significantly associated with levels of overt ASB across a 6-year period. Only deviant peer affiliation was significantly related to covert ASB, however. Additionally, there was evidence suggestive of a gene-environment interaction (G × E) where the influence of deviant peer affiliation on overt ASB was significantly stronger among individuals with the high-activity MAOA genotype than the low-activity genotype. MAOA was not significantly associated with deviant peer affiliation, thus strengthening the inference of G × E rather than gene-environment correlation (rGE). Different forms of gene-environment interplay and implications for future research on ASB are discussed.     

A twin study of the association between pathological gambling and antisocial personality disorder

Many individuals with a history of pathological gambling (PG) also have a history of engaging in antisocial behaviors, and this has often been interpreted as a result of the former causing the latter. In a sample of 7,869 men in 4,497 twin pairs from the Vietnam Era Twin Registry, the authors examined (a) the association between PG and antisocial personality disorder (ASPD), (b) the extent to which PG might be differentially associated with childhood conduct disorder (CD) and adult antisocial behavior (AAB), and (c) the contribution of genetic and environmental factors to the association of PG with ASPD, CD, and AAB. PG was significantly associated with all 3 antisocial behavior disorders, and the association of PG with ASPD, CD, and AAB was predominantly explained by genetic factors. The results of this study suggest that the greater-than-chance co-occurrence of PG and antisocial behavior disorders is partially due to their sharing a common genetic vulnerability. The antisocial behavior observed among many individuals with PG probably cannot be interpreted as being simply a consequence of the PG.     

The Genetic and Psychophysiological Basis of Antisocial Behavior: Implications for Counseling and Therapy

The notion that crime may have a genetic and biological basis has been resisted due to the assumption that this view necessitates a deterministic attitude to crime. This article argues that this assumption is unwarranted, and that an understanding of the genetic and psychophysiological basis of crime and antisocial behavior has important implications for counselors dealing with antisocial individuals. The interaction between genetic and environmental factors suggests that environmental changes may reduce the expression of any genetic predisposition. Psychophysiological factors interact with social factors in producing antisocial behavior, and recent psychophysiological studies have identified enhanced attentional ability in antisocial individuals that can be capitalized on by counselors in diverting clients from an antisocial way of life.     

Cognition to genes via the brain in the study of conduct disorder

Although a single diagnostic label, conduct disorder, is currently applied to children exhibiting antisocial behaviour, multiple routes to the same behavioural phenomena exist. Morton and Frith's (1995) causal modelling has been fundamentally important in influencing models of cognitive/affective and associated neural differences between callous-unemotional (CU) and reactive/threat-based antisocial behaviour. Current behavioural genetic research is still catching up with the developmental cognitive neuroscience, and very few genetically informative studies differentiate between these two subtypes of antisocial behaviour. Our own work with preadolescent twins suggests that while the CU subtype is genetically vulnerable to antisocial behaviour, the non-CU subtype manifests a primarily environmental aetiology to their antisocial behaviour. Molecular genetic work to date has not differentiated between these two subtypes, and we highlight why it might be of interest to do so. Finally, we discuss how the novel approach of imaging genetics could be harnessed to study genes to cognition pathways for different subtypes of conduct disorder. Uta Frith's contributions to articulating research strategies for developmental disorders are important in conducting and interpreting this work.