NR3C1基因Bcl1多态性与青少年抑郁：压力性生活事件的调节作用

迄今,有关抑郁的基因×环境交互研究多数基于“单胺缺陷假说”,相对较少有研究以“HPA轴假说”为框架考察抑郁的遗传机制,且忽视了基因-环境相关的影响。本研究对1081名青少年进行追踪研究,考察NR3C1基因Bcl1多态性与压力性生活事件对抑郁的影响。结果发现,经历较多压力性事件时,C等位基因携带者的抑郁水平显著高于GG纯合子携带者;经历较少压力性事件时,不同基因型携带者的抑郁水平无差异。此外,通过区分独立性压力性事件和预测早期抑郁进一步排除了基因-环境相关的影响,在一定程度上验证了结果的可靠性。     

MAOA基因rs6323多态性与母亲支持性教养对青少年抑郁的交互作用：素质-压力假说与不同易感性假说的检验

抑郁的遗传与环境交互作用(G×E)机制已成为富有挑战性的前沿课题之一。然而,既有G×E研究大多关注遗传基因与不利环境的交互作用,相对忽视了积极环境的影响。本研究以1025名青少年为被试,运用问卷法与 DNA分型技术,采用间隔3年的追踪设计(T1小学六年级—T2初中三年级),考察 MAOA基因rs6323多态性与母亲支持性教养对青少年抑郁的交互作用以及性别在其中的调节作用,并同时采用新兴的探索性与验证性方法检验G×E交互作用的素质–压力假说与不同易感性假说。结果显示, MAOA基因rs6323多态性与母亲支持性教养行为交互作用于女青少年的抑郁,母亲支持性教养显著负向预测 GG 基因型女青少年的抑郁,但对 TT基因型女青少年抑郁的预测作用并不显著,该交互作用符合不同易感性假说。MAOA基因 rs6323多态性与母亲支持性教养对男青少年的抑郁无显著交互作用。本研究发现推进了抑郁遗传机制的研究,并为不同易感性假说提供新的研究证据。     

TPH2基因rs4570625多态性和母亲权威教养对创造力的交互作用

采用基因分型技术、自我报告及表现性评价对409名健康的中国汉族大学生的基因型、母亲教养方式、一般智力和创造力进行测量,综合运用分层回归分析和显著性区域分析（regions of significance, RoS）方法探讨了TPH2基因rs4570625多态性与母亲权威教养对创造力的交互作用及其交互作用模式。结果发现：（1）在创造力的流畅性和独创性维度上,rs4570625多态性和母亲权威存在显著的交互作用。（2）RoS分析结果均支持差别易感模型,T等位基因是母亲权威的“可塑性”基因。这些发现将有助于从遗传和环境相互作用的角度解释个体创造力差异的起源。     

Serotonin transporter 5-HTTLPR genotype is associated with intrusion and avoidance symptoms of DSM-5 posttraumatic stress disorder (PTSD) in Chinese earthquake survivors

Background and Objectives: Prior studies have found that the serotonin transporter gene-linked polymorphic region (5-HTTLPR) interacts with trauma exposure to increase general risk for Posttraumatic Stress Disorder (PTSD). However, there is little knowledge about the effects of the interaction on distinct symptom clusters of PTSD. This study aimed to investigate the relation between the interaction of 5-HTTLPR and earthquake-related exposures and a contemporary phenotypic model of DSM-5 PTSD symptoms in a traumatised adult sample from China.

Design: A cross-sectional design with gene-environment interaction (G?×?E) approach was adopted. Methods: Participants were 1131 survivors who experienced 2008 Wenchuan earthquake. PTSD symptoms were assessed with the PTSD Checklist for DSM-5 (PCL-5). The 5-HTTLPR polymorphism was genotyped with capillary electrophoresis (CE) in ABI 3730xl genetic Analyzer.

Results: Although there was no significant interaction between 5-HTTLPR and traumatic exposure on total PTSD symptoms, respondents with the LL genotype of 5-HTTLPR who were highly exposed to the earthquake experienced lower intrusion and avoidance symptoms than those with the S-allele carriers.

Conclusions: The findings suggest that the 5-HTTLPR may have an important impact on the development of PTSD and add to the extant knowledge on understanding and treating of posttraumatic psychopathology.     

Children's 5-HTTLPR genotype moderates the link between maternal criticism and attentional biases specifically for facial displays of anger

Theorists have proposed that negative experiences in childhood may contribute to the development of experience-specific information-processing biases, including attentional biases. There are also clear genetic influences on cognitive processes, with evidence that polymorphisms in specific candidate genes may moderate the impact of environmental stress on attentional biases (e.g., a functional polymorphism in the serotonin transporter gene; 5-HTTLPR). In the current study, we tested a gene×environment (G×E) model of risk for attentional biases. We hypothesised that children whose mothers exhibit high levels of expressed emotion criticism (EE-Crit) would display attentional biases specifically for angry, but not happy or sad, faces, and that this link would be stronger among children carrying one or two copies of the 5-HTTLPR short allele than among those homozygous for the long allele. Results generally supported these hypotheses, though we found that carriers of the 5-HTTLPR short allele who also had a critical mother exhibited attentional avoidance of angry faces rather than preferential attention.     

5-HTTLPR与抑郁相关性的研究动态

摘 要 5-HTTLPR是5-羟色胺转运蛋白基因启动子区域上的多态性位点,对其转录效率具有调节作用。5-HTTLPR基因型与抑郁存在相关,但必须把二者的关系置于一个多基因与环境交互作用的框架下考察。一方面,环境因素的作用不容忽视：S等位基因携带者暴露于负性生活事件时,表现出更多情绪问题,更易发生抑郁。另一方面,CYP2C9、BDNF等基因与5-HTTLPR有交互作用,共同影响抑郁的发生。此外,年龄、性别等因素会对研究结果造成混淆。未来研究应侧重于对机制的探讨。     

Factors Influencing Men's Interest in Gene Testing for Prostate Cancer Susceptibility

Interest in genetic testing for inherited cancer susceptibility is high in the general population. Women at risk for BRCA1 and BRCA2 mutations represent the best-studied population undergoing genetic testing for cancer susceptibility. However, it is unclear whether factors influencing interest in genetic testing in women are directly applicable to men. We designed a study to examine factors associated with men's interest in genetic testing to identify prostate cancer susceptibility. Our sample consisted of 267 men present in waiting rooms of a urology clinic in an urban area. We examined whether the concept of monitoring could be used to predict the interest of men in a genetic test for prostate cancer susceptibility. Our results indicated that monitoring trait was positively associated with interest in genetic testing in these men, but principally for patients rather than nonpatients. Moreover we found that monitoring was associated with over estimation of risk in those men with prostate cancer. Other factors found to influence interest in genetic testing included recommendation by a doctor, family history of prostate cancer, and cost. This study indicated that interest in genetic testing and estimation of risk is influenced by a complex interaction between both psychological factors (monitoring) and nonbehavioral factors (such as patient status, cost, and doctor recommendation).     

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.     

5-HTTLPR基因多态性和早期养育压力对学前儿童问题行为的影响

本研究拟探讨5-HTTLPR基因多态性与母亲早期养育压力对中国汉族学前儿童问题行为的交互作用机制和性别差异。355名6个月婴儿及其父母参加了本研究。在婴儿6个月时，收集婴儿的口腔脱落细胞和母亲养育压力数据；在48个月时，再次邀请父母分别报告儿童的问题行为。结果发现：（1）当母亲养育压力较高时，s/s和s/l型男孩的外显问题行为显著高于l/l型男孩；但当母亲养育压力较低时，两组男孩没有显著差异；（2）当母亲养育压力较高时，l/l型女孩的内隐问题行为显著高于s/s和s/l型女孩；但当母亲养育压力较低时，两组女孩没有显著差异。研究结果表明，5-HTTLPR基因多态性与母亲养育压力在预测男孩外显问题行为和女孩内隐问题行为时的交互作用机制均支持素质-压力模型。     

Examining the association between MAOA genotype and incarceration, anger and hostility: The moderating influences of risk and protective factors

Findings from molecular genetic research have indicated that a polymorphism in the promoter region of the MAOA gene interacts with environmental liabilities to predict antisocial phenotypes. We use these findings as a springboard to examine whether a global protective-risk factor index moderates the effect of MAOA genotype on the probability of being incarcerated and on a measure of anger and hostility. Analysis of data from the National Longitudinal Study of Adolescent Health (Add Health) indicates that exposure to risk and protective factors in adolescence are able to moderate the effect of MAOA genotype on anger and hostility in adulthood for males. The results in relation to the probability of being incarcerated were consistently null.     

Interactions between early parenting and a polymorphism of the child's dopamine transporter gene in predicting future child conduct disorder symptoms

Mounting evidence suggests that genetic risks for mental disorders often interact with the social environment, but most studies still ignore environmental moderation of genetic influences. The authors tested interactions between maternal parenting and the variable number tandem repeat (VNTR) polymorphism in the 3' untranslated region of the dopamine transporter gene in the child to increase understanding of gene-environment interactions involving early parenting. Participants were part of a 9-year longitudinal study of 4- to 6-year-old children who met criteria for attention-deficit/hyperactivity disorder (ADHD) and demographically matched controls. Maternal parenting was observed during standard mother-child interactions in Wave 1. The child's conduct disorder (CD) symptoms 5-8 years later were measured using separate structured diagnostic interviews of the mother and youth. Controlling for ADHD symptoms and child disruptive behavior during the mother-child interaction, there was a significant inverse relation between levels of both positive and negative parenting at 4-6 years and the number of later CD symptoms, but primarily among children with 2 copies of the 9-repeat allele of the VNTR. The significant interaction with negative parenting was replicated in parent and youth reports of CD symptoms separately.     

Association of Positive and Negative Parenting Behavior with Childhood ADHD: Interactions with Offspring Monoamine Oxidase A (MAO-A) Genotype

Relatively little is known about the potential interplay between genetic and environmental influences on attention-deficit/hyperactivity disorder (ADHD), including gene-environment interaction (G×E). There is evidence that parenting behavior interacts with offspring genotype in the development of externalizing problems, but studies have largely focused on explicit maltreatment rather than differentiated measures of parenting behavior, including positive and negative parenting. We tested the interactive effects of the 30-base pair variable number tandem repeat (VNTR) polymorphism of the monoamine oxidase A gene (MAO-A) with positive and negative parenting behavior on parent- and teacher ratings of inattention and hyperactivity symptoms among 150 6–9 year-old boys with and without ADHD. Negative parenting predicted parent and teacher ratings of inattention symptoms, but only among boys with high-activity MAO-A genotype. MAO-A genotype did not moderate the association of positive parenting and parent- and teacher ratings of ADHD. We discuss the potential role of interactive exchanges between parenting behavior and child genotype in the development and persistence of ADHD and related behavior problems.     

DRD4基因与亲社会行为的关联及其潜在脑机制

DRD4基因是亲社会行为的重要候选基因,且与环境交互影响亲社会行为的发生发展。通过梳理既有研究,本文从性别差异、亲社会行为的不同类型及发展动态性等角度探讨了亲社会行为遗传研究存在分歧的原因,并在此基础上探索了DRD4基因作用于亲社会行为的潜在脑机制。未来研究应采用纵向设计探究DRD4基因影响亲社会行为的发展动态性问题,并深入探索其性别差异;采用多质多法分析考察不同类型亲社会行为遗传机制的差异性;采用影像遗传学设计揭示“DRD4基因—脑—亲社会行为”作用机制。     

Socioenvironmental experiences,self-esteem,and emotional/behavioral problems in early adolescence

Tested the role of self-esteem as a mediator of relationships between socioenvironmental experiences and emotional/behavioral problems using a sample of 215 young adolescents (Grades 7–9). Socioenvironmental experiences were assessed using self-report questionnaire measures of social support and major and minor stressful events. Self-esteem was assessed using a self-report questionnaire, an interview, and a parent-report questionnaire. Emotional/behavioral problems were assessed using self-report, parent-report and teacherreport questionnaires. Utilizing structural equation modeling, the data were used to test a model in which self-esteem mediated the relationship between socioenvironmental experiences and emotional/behavioral problems. The hypothesized model provided a reasonably good fit to the data (normed fit index=.90). However, an alternative model which also allowed for direct effects of socioenvironmental experiences on emotional/behavioral problems produced a significant improvement in model fit. In this model, socio-environmental experiences had significant effects on emotional problems via both direct effects and indirect effects that indicated a mediating role for self-esteem. Only direct effects of socioenvironmental experiences were evident for behavioral problems. This research was supported by a grant to the first author from the University of Missouri Research Board. Thanks are due to the students, staff, and parents of the Columbia Public Schools, Columbia, Missouri, for their participation in and support of this research project.     

Association between polymorphisms in the dopamine transporter gene and depression: evidence for a gene-environment interaction in a sample of juvenile detainees

Previous research has generated examples of how genetic and environmental factors can interact to create risk for psychopathology. Using a gene-by-environment (G x E) interaction design, we tested whether three polymorphisms in the dopamine transporter gene (DAT1, also referred to as SLC6A3, located at 5p15.33) interacted with maternal parenting style to predict first-onset episodes of depression. Participants were male adolescents (N= 176) recruited from a juvenile detention center in northern Russia. As hypothesized, one of the polymorphisms (rs40184) moderated the effect of perceived maternal rejection on the onset of major depressive disorder, as well as on suicidal ideation. Further, this G x E interaction was specific to depression; it did not predict clinically significant anxiety. These results highlight the need for further research investigating the moderating effects of dopaminergic genes on depression.     

MAOA基因T941G多态性与同伴侵害对男青少年早期抑郁的交互作用:COMT基因Val158Met多态性的调节效应

抑郁具有复杂的多基因遗传基础,然而既有研究大多采用单基因以及单基因-环境交互设计(G×E)考察抑郁的遗传机制。以757名男青少年为被试(初次测评时Mage=11.32岁,SD=0.49岁),采用多基因-环境交互(G×G×E)设计,本研究考察了MAOA(monoamine oxidase A,单胺氧化酶A)基因T941G多态性、COMT(catechol-O-methyltransferase,儿茶酚胺氧位甲基转移酶)基因Val158Met多态性与同伴侵害对青少年早期抑郁的影响。结果显示,MAOA基因T941G多态性与同伴侵害交互作用于青少年抑郁,同伴侵害仅显著正向预测G等位基因(而非T等位基因)青少年抑郁。而且,MAOA基因T941G多态性与同伴侵害的交互作用受到COMT基因Val158Met多态性的调节,上述交互作用仅存在于COMT Met等位基因而非Val/Val基因型携带者中。研究结果显示,抑郁的产生与个体差异存在多基因与环境间的复杂交互机制。     

Type D personality and the development of PTSD symptoms: a prospective study

Psychological trauma and prolonged stress may cause mental disorders such as posttraumatic stress disorder (PTSD). Pretrauma personality is an important determinant of posttraumatic adjustment. Specifically, trait neuroticism has been identified as a risk factor for PTSD. Additionally, the combination of high negative affectivity or neuroticism with marked social inhibition or introversion, also called Type D personality (Denollet, 2000), may compose a risk factor for PTSD. There is no research available that examined pretrauma Type D personality in relation to PTSD. The present study examined the predictive validity of the Type D personality construct in a sample of Dutch soldiers. Data were collected prior to and 6 months after military deployment to Afghanistan. Separate multiple regression analyses were performed to examine the predictive validity of Type D personality. First, Type D personality was defined as the interaction between negative affect and social inhibition (Na × Si). In a second analysis, Type D was defined following cutoff criteria recommended by Denollet (2000). Results showed that negative affectivity was a significant predictor of PTSD symptoms. Social inhibition and the interaction Na × Si did not add to the amount of explained variance in postdeployment PTSD scores over the effects of childhood abuse, negative affectivity, and prior psychological symptoms. A second analysis showed that Type D personality (dichotomous) did not add to the amount of explained variance in postdeployment PTSD scores over the effects of childhood abuse, and prior psychological symptoms. Therefore, Type D personality appears to be of limited value to explain development of combat-related PTSD symptoms.     

Understanding risk for psychopathology through imaging gene-environment interactions

Examining the interplay of genes, experience and the brain is crucial to understanding psychopathology. We review the recent gene-environment interaction (G×E) and imaging genetics literature with the goal of developing models to bridge these approaches within single imaging gene-environment interaction (IG×E) studies. We explore challenges inherent in both G×E and imaging genetics and highlight studies that address these limitations. In specifying IG×E models, we examine statistical methods for combining these approaches, and explore plausible biological mechanisms (e.g. epigenetics) through which these conditional mechanisms can be understood. Finally, we discuss the potential contribution that IG×E studies can make to understanding psychopathology and developing more personalized and effective prevention and treatment.     

The link between maternal interaction style and infant action understanding

The present study investigates whether the maternal interaction style is related to 6-month-old infants' action interpretation. We tested 6-month-olds ability to interpret an unfamiliar human action as goal-directed using a modified version of the paradigm used by Woodward, A. L. (1999). Infant's ability to distinguish between purposeful and non-purposeful behaviours. Infant Behavior & Development, 22, 145-160 and Király, I., Jovanovic, B., Prinz, W., Aschersleben, G., & Gergely, G. (2003). The early origins of goal attribution in infancy. Consciousness & Cognition, 12, 732-751. Additionally, all infants and their mothers participated in a free play situation to assess maternal interaction styles as measured by the CARE-Index. According to mothers' distinct interaction styles, infants were divided into three groups. Results suggest that at 6 months of age infants of mothers with a modestly controlling interaction style are better at interpreting a human action as goal-directed than infants of sensitive and relative unresponsive mothers. The ability to understand human action as goal-directed might be a corollary of an adaptive strategy in infancy.