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。     

父母教养行为与青少年早期抑郁的关系：多基因与负性生活事件的调节作用

以745名青少年为被试,采用多基因×多环境设计,考察COMT Val158Met、5-HTR1A C-1019G和BDNF Val66Met基因多态性的多基因累加得分与负性生活事件在父母教养行为与青少年早期抑郁之间的调节作用及其性别差异。结果发现,多基因累加得分与负性生活事件仅能显著调节父亲积极教养行为对青少年抑郁的预测作用,且该调节作用只存在于男青少年群体中。研究结果丰富了抑郁的多基因遗传机制研究,为制定青少年早期抑郁的干预措施提供了理论依据。     

负性生活事件与青少年早期抑郁的关系：COMT基因Val158Met多态性与父母教养行为的调节作用

采用环境×基因×环境(E×G×E)研究设计, 以637名青少年为被试, 考察了负性生活事件、COMT基因Val158Met多态性和父母教养行为对青少年早期抑郁的影响。结果发现：负性生活事件对青少年早期抑郁具有显著正向预测作用, 且COMT基因Val158Met多态性和父亲积极教养行为在其中起调节作用, 但该调节作用仅存在于男青少年群体中：在携带Val/Val基因型的男青少年中, 当父亲积极教养行为水平较低时, 青少年的抑郁水平随负性生活事件的增多而显著上升, 当父亲积极教养行为水平较高时, 负性生活事件对抑郁无显著预测作用; 在携带Met等位基因的男青少年中, 上述交互作用不显著。     

COMT基因Val158Met多态性与同伴关系对青少年抑郁的影响

以1048名汉族青少年为被试,采用问卷法和基因分型技术,综合运用传统回归分析和新兴的再参数化回归分析,考察COMT基因Val158Met多态性与同伴关系对青少年抑郁的交互作用模式及其性别差异。结果发现,COMT基因与同伴接纳和同伴拒绝交互预测青少年抑郁,具体表现为,在低同伴接纳或高同伴拒绝环境中,携带ValVal基因型的青少年抑郁水平高于Met等位基因携带者;在高同伴接纳或低同伴拒绝环境中,携带ValVal基因型的青少年抑郁水平低于Met等位基因携带者。此外,COMT基因与同伴接纳和同伴拒绝的交互作用与男生抑郁的关联更加密切。结果显示,COMT基因与同伴关系的交互效应为不同易感性模型提供了证据,而且该基因×环境交互效应存在性别差异。     

人类情绪记忆的行为遗传学与神经遗传学研究进展述评

情绪记忆及其增强效应存在广泛的个体差异,这种个体差异可能有其神经与遗传基础。近来的行为遗传学与神经遗传学证实人类ADRA2B基因缺失突变以及BDNF Val66Met基因的多态性与情绪记忆增强及其神经机制的个体差异相联系。本文重点介绍与人类情绪记忆相关的这两种基因,梳理了行为与神经遗传学研究的最新进展,指出未来应关注更多候选基因,并重视多个脑区之间的交互作用;还应使用情绪面孔刺激探索BDNF Val66Met基因多态性对情绪记忆编码和提取的影响等。     

COMT多态性与连续3-back任务相关ERP的关联研究

不同COMT基因型被试者,进行连续3-back任务测试,以探讨被试者工作记忆能力的变化情况。抽取21名不同COMT基因型被试者,观测被试者在连续工作记忆任务中记忆能力和脑电生理的差异。结果表明,Val/Met基因型被试者P300波幅显著低于Val/Val型,Met/Met型被试者的P300波幅居中。Val/Met型被试者显示了最差记忆任务成绩,被试者的P300波幅和记忆能力相关。COMT基因多态性和3-back任务事件相关电位相关联,工作记忆任务的灵活性和稳定性及其交互作用受到遗传因素的调控。     

COMT基因对注意控制神经基础的调控效应：影像遗传学研究的元分析

为探索注意控制能力个体差异的遗传来源, 当前研究主要关注儿茶酚胺氧位甲基转移酶(catechol-O-Methyltransferase, COMT)基因对参与注意控制加工的前额叶脑区的调控作用。为进一步回答COMT基因是否也对全脑范围的注意脑区具有调控作用, 本文对17篇遗传影像学研究进行元分析。结果发现, COMT基因Val/Val (vv)基因型的被试在注意控制任务下, 不仅前额叶脑区的激活水平高于Met/Met(mm)基因型的被试, 在前扣带回和后扣带回等前额叶之外的脑区激活水平也高于mm基因型的被试, 而且在这些脑区的效应值(vv>mm)都较大(Cohen’s d > 0.8)。由此, 元分析结果表明：COMT基因不仅调控前额叶脑区, 而且对形成注意控制网络的多个脑区都有调控效应。此结果提示注意控制能力的个体差异可能部分的来自于COMT基因对注意控制网络的调控作用。     

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。     

手机成瘾与抑郁：社交焦虑和负性情绪信息注意偏向的多重中介作用

为考察手机成瘾与抑郁的关系, 研究同时整合情绪和认知两方面因素, 探讨了社交焦虑和负性情绪信息注意偏向在手机成瘾和抑郁之间的多重中介作用。研究1共有545名大学生完成了大学生手机成瘾倾向量表、贝克抑郁量表和社会交往焦虑量表。研究2选取51名大学生采用问卷法和2(配对面孔表情的情绪类型: 负性、中性) × 2(探测点位置: 与负性情绪面孔表情同侧、与负性情绪面孔表情异侧)的被试内实验设计。结果表明: (1)手机成瘾、社交焦虑和抑郁两两间存在显著正相关, 且社交焦虑在手机成瘾和抑郁之间起完全中介作用; (2)社交焦虑和负性情绪信息注意偏向在手机成瘾与抑郁的关系中起链式中介作用, 而负性情绪信息注意偏向在手机成瘾与抑郁间的单独中介效应不显著。具体而言, 手机成瘾通过两条路径影响抑郁: 一是社交焦虑的单独中介作用; 二是社交焦虑→负性情绪信息注意偏向的链式中介作用。     

8~12岁儿童抑郁与认知重评的关系：悲伤面孔注意偏向的中介作用

探讨8~12岁学龄儿童抑郁与认知重评情绪调节策略的关系及其作用机制。研究1采用问卷法和行为实验法分别考察儿童抑郁对认知重评策略使用倾向和使用能力的作用; 研究2结合眼动技术考察对情绪信息注意偏向在儿童抑郁和认知重评关系间的中介作用。结果发现：(1) 抑郁与儿童认知重评使用倾向间存在显著负相关; (2) 抑郁对儿童负性情绪向下调节的重评效果有显著影响; (3) 悲伤面孔注意解除困难在抑郁与认知重评使用倾向之间起中介作用。     

How to consistently link extraversion and intelligence to the catechol-O-methyltransferase (COMT) gene: on defining and measuring psychological phenotypes in neurogenetic research

The evidence for associations between genetic polymorphisms and complex behavioral/psychological phenotypes (traits) has thus far been weak and inconsistent. Using the well-studied Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene as an example, we demonstrate that using theoretical models to guide phenotype definition and measuring the phenotypes of interest with a high degree of specificity reveals strong gene-behavior associations that are consistent with prior work and that would have otherwise gone unnoticed. Only after statistically controlling for irrelevant portions of phenotype variance did we observe strong (Cohen's d = 0.33-0.70) and significant associations between COMT Val158Met and both cognitive and affective traits in a healthy male sample (N = 201) in Study 1: Carriers of the Met allele scored higher in fluid intelligence (reasoning) but lower in both crystallized intelligence (general knowledge) and the agency facet of extraversion. In Study 2, we conceptually replicated the association of COMT Val158Met with the agency facet of extraversion after partialing irrelevant phenotype variance in a female sample (N = 565). Finally, through reanalysis of a large published data set we showed that Met allele carriers also scored higher in indicators of fluid intelligence after partialing verbal fluency. Because the Met allele codes for a less efficient variant of the enzyme COMT, resulting in higher levels of extrasynaptic prefrontal dopamine, these observations provide further support for a role for dopamine in both intelligence and extraversion. More importantly, the present findings have important implications for the definition of psychological phenotypes in neurogenetic research.     

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。     

Warriors versus worriers: the role of COMT gene variants

Behavioral phenotypes are generally complex, reflecting the action of multiple different genes. Nevertheless, there is growing evidence that key gene variants can alter activity within specific neuronal circuits and, therefore, influence particular cognitive-affective phenomena. One example is the catechol-O-methyltransferase (COMT) gene, which has a common variant at codon 158. Those with valine (Val158) alleles have increased greater COMT activity and lower prefrontal extracellular dopamine compared with those with the methionine (Met158) substitution. Val158 alleles may be associated with an advantage in the processing of aversive stimuli (warrior strategy), while Met158 alleles may be associated with an advantage in memory and attention tasks (worrier strategy). Under conditions of increased dopamine release (eg, stress), individuals with Val158 alleles may have improved dopaminergic transmission and better performance, while individuals with Met158 alleles may have less efficient neurotransmission and worse performance. Some evidence suggests that Val158 alleles are associated with schizophrenia, while Met158 alleles are associated with anxiety.     

Influence of brain-derived neurotrophic factor and catechol O-methyl transferase polymorphisms on effects of meditation on plasma catecholamines and stress

Meditation may show differential effects on stress and plasma catecholamines based on genetic polymorphisms in brain-derived neurotrophic factor (BDNF) and catechol O-methyl transferase (COMT). Eighty adults (40 men, 40 women; mean age 26 years) who practiced meditation regularly and 57 healthy control adults (35 men, 22 women; mean age 26 years) participated. Plasma catecholamines (norepinephrine (NE), epinephrine (E), and dopamine (DA)) concentrations were measured, and a modified form of the Stress Response Inventory was administered. The results were analyzed using two-way analysis of covariance (ANCOVA) with control and meditation subjects, gene polymorphism as factors, and meditation duration as the covariate. Two-way ANCOVA showed a significant interaction between control and meditation subjects, and BDNF Val66Met polymorphism on DA/NE+DA/E (p = 0.042) and NE/E+NE/DA (p = 0.046) ratios. A significant interaction was found for control and meditation subjects with COMT Val158Met polymorphism and plasma NE concentrations (p = 0.009). Post hoc ANCOVA in the meditation group, adjusted for meditation duration, showed significantly higher plasma NE concentrations for COMT Met carriers than COMT Val/Val subjects (p = 0.025). Significant differences of stress levels were found between the control and meditation subjects in BDNF Val/Met (p < 0.001) and BDNF Met/Met (p = 0.003), whereas stress levels in the BDNF Val/Val genotype did not differ between the control and meditation groups. This is the first evidence that meditation produces different effects on plasma catecholamines according to BDNF or COMT polymorphisms.     

Association of catechol-O-methyltransferase (COMT) polymorphism and academic achievement in a Chinese cohort

Catechol-O-methyltransferase (COMT) is a methylation enzyme that catalyzes the degradation pathway and inactivation of dopamine. It is accepted widely as being involved in the modulation of dopaminergic physiology and prefrontal cortex (PFC) function. The COMT Val158Met polymorphism is associated with variation in COMT activity. COMT 158Met allele may be advantageous for PFC-related cognitive abilities; however, it is also associated with increased anxiety, depression, and emotional vulnerability in response to stress or educational adversity. We hypothesized that the COMT polymorphism might be associated with academic performance. In this study, 779 Taiwanese tenth-grade volunteers were recruited. Scores from the Basic Competency Test (BCT), an annual national competitive entrance examination, were used to evaluate academic performance. The results indicated that students bearing homozygous for the Met allele tended to perform more poorly in all BCT subtests as compared to the other groups. In particular, the former performed significantly more poorly in the science and social science subtests. These findings provide evidence that affective factors might overwhelm cognitive abilities in high-stake tests like the BCT.     

Association of catechol-O-methyltransferase (COMT) polymorphism and academic achievement in a Chinese cohort

Catechol-O-methyltransferase (COMT) is a methylation enzyme that catalyzes the degradation pathway and inactivation of dopamine. It is accepted widely as being involved in the modulation of dopaminergic physiology and prefrontal cortex (PFC) function. The COMT Val158Met polymorphism is associated with variation in COMT activity. COMT 158Met allele may be advantageous for PFC-related cognitive abilities; however, it is also associated with increased anxiety, depression, and emotional vulnerability in response to stress or educational adversity. We hypothesized that the COMT polymorphism might be associated with academic performance. In this study, 779 Taiwanese tenth-grade volunteers were recruited. Scores from the Basic Competency Test (BCT), an annual national competitive entrance examination, were used to evaluate academic performance. The results indicated that students bearing homozygous for the Met allele tended to perform more poorly in all BCT subtests as compared to the other groups. In particular, the former performed significantly more poorly in the science and social science subtests. These findings provide evidence that affective factors might overwhelm cognitive abilities in high-stake tests like the BCT.