COMT基因Val158Met多态性与抑郁的关系

抑郁的发生具有重要的遗传学基础。COMT基因Val158Met多态性是抑郁的重要候选基因位点。目前有关COMT基因Val158Met多态性与抑郁关系的研究主要采用单基因设计、单基因-环境设计以及多基因-环境设计。有资料显示负性情绪偏向及其相关脑区可能在COMT基因Val158Met多态性与抑郁间起中介作用, 但具体机制仍有待探究。未来研究可以进一步考察被试的种族、年龄和性别等因素对COMT基因Val158Met多态性与抑郁关系的调节作用, 并通过采用多基因-环境设计, 综合运用积极与消极环境指标等措施深入考察负性情绪偏向和相关脑区在COMT基因Val158Met多态性与抑郁间的作用及其机制。     

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。     

急性应激对工作记忆的影响受工作记忆负荷调节:来自电生理的证据

急性应激如何影响工作记忆还不清楚。采用电影片断诱发被试的急性应激或中性状态后,让其完成数字N-back任务并同时记录脑电。结果发现,低负荷工作记忆诱发的P3显著大于高负荷工作记忆;在0-back任务中,急性应激组诱发的P3显著大于控制组;而在2-back任务中,这种差异不显著。这些结果表明急性应激对工作记忆的影响受工作记忆负荷调节,支持了双竞争理论模型。     

音乐对工作记忆影响及机制的ERP研究

以肖邦音乐为刺激材料,采用数字n-back实验范式来研究肖邦音乐对工作记忆的影响方式,并通过运用事件相关电位技术(ERP技术),研究不同音乐条件下,正常人大脑皮层的脑电活动情况,进而探讨音乐对工作记忆影响的神经机制。30名被试参加了3种音乐条件(无音乐、先导音乐、背景音乐)下的n-back(n=1、2)工作记忆任务的行为实验,收集行为数据;14名被试参加了同样实验过程的ERP实验,记录脑电数据。行为结果发现音乐条件对工作记忆效果有显著影响,且先导音乐条件下记忆效果最好;脑电结果显示P3波幅随记忆负荷的增加呈下降趋势,高记忆负荷水平下,P3波幅随先导音乐、背景音乐、无音乐的顺序逐渐呈现下降趋势;源定位分析发现音乐对工作记忆的促进作用可能跟大脑顶叶被激活有关。     

药物相关线索干扰海洛因戒断者的刷新能力

研究采用n-back任务,检验药物相关线索对海洛因戒断者工作记忆刷新的影响,旨在探究海洛因戒断者由于长期药物使用造成的认知损伤和药物相关线索之间的关系。结果显示:（1）无论在1-back任务中还是在2-back任务中,相对于正常人,海洛因戒断者反应时长更长。（2）相对于中性线索条件,海洛因戒断者在药物相关线索条件下的反应时更长;（3）相对于2-back任务,正常人与海洛因戒断者在1-back任务中的正确率更高。这可能表明长期的药物使用会使海洛因成瘾戒断者的工作记忆刷新能力受损,而药物相关线索会进一步干扰这种认知损伤。     

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。     

任务无关情绪刺激对工作记忆信息更新的影响:来自ERP的证据

任务无关的情绪刺激如何对工作记忆的信息更新过程产生影响还不清楚。本研究采用情绪N-back任务,结合事件相关电位技术调查情绪对工作记忆信息更新的影响。ERP结果显示,在0-back任务中,负性分心物诱发的P3显著小于中性分心物,表明其干扰了工作记忆信息更新过程;而在2-back任务中,负性分心物诱发的P3与中性分心物没有显著差异,表明其未对信息更新表现出干扰效应。该结果支持了情绪与认知加工的双竞争模型。     

工作记忆刷新功能上的自我加工优势:来自虚拟物品识别的证据

通过采用所有权范式和n-back范式,将70名大学生随机分为2组,2组被试分别完成1-back和2-back任务,探讨了工作记忆中自我相关信息的刷新特点。结果发现:(1)低记忆负荷下的正确率显著高于高记忆负荷,且反应时显著快于高记忆负荷。(2)自我物品与他人物品在正确率上无显著差异。(3)自我物品的反应时显著快于他人物品。这说明无论记忆负荷高低,在工作记忆刷新功能上始终存在自我加工优势,主要表现在对自我相关信息的刷新速度上。     

短时存贮与复述动态分离的ERP证据

工作记忆参与信息的短时贮存和操作加工。为了分离参与词语短时存贮与复述的脑区及其时间过程,测量并比较了14名正常青年被试进行汉字2-back、0-back和复述任务时的事件相关电位(ERPs)。结果发现,2-back任务减复述任务在头皮后部出现差异波N430,可能反映了信息的短时存贮及其时间进程。2-back任务减0-back任务在头皮前部得到的持续负成分SNC可能是复述加工的动态指标。SNC和N430持续时间的重叠提示,大脑额叶和后部区域分别参与信息的复述和短时存贮,两者的动态分离加工可能是工作记忆中暂时保持的神经基础。     

视觉工作记忆内容对自上而下注意控制的影响：一项ERP研究

采用视觉搜索范式, 以二维抽象对称图形为材料, 通过记录\16名被试在长短两种时间间隔(ISI)条件和有效、中性、无效三种视觉工作记忆内容条件下的行为反应和事件相关电位(ERPs), 探讨视觉工作记忆内容对自上而下注意控制影响的认知过程和脑机制。结果发现：(1)无论ISI长或短, 有效信息条件(记忆图形与目标所在的背景图形相同)的反应时均显著短于无效信息条件(记忆图形与目标所在的背景图形不同)。(2)有效信息条件下的额区P2波幅显著大于中性信息条件(记忆图形不出现在搜索序列中); 枕区P1、N1波幅和潜伏期在视觉工作记忆内容条件下差异不显著; 短ISI条件下, 有效信息条件下的枕区P300波幅显著大于无效信息条件; 长ISI条件下, 有效信息条件的枕区P300波幅显著小于无效信息条件。表明当目标出现在与记忆内容相匹配的客体中时, 激活了工作记忆中的客体表征, 以自上而下的方式优先捕获注意; 同时ISI变化对此过程起着调节作用。     

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.     

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.     

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.     

Schoolchildren’s autobiographical memory: COMT gene Val158Met polymorphism effects on emotional content and quality of first memories

Cognitive Processing - Autobiographical memory is a cognitive function strongly related to emotional processing as autobiographical memory often includes emotional content. The COMT gene Val158Met...     

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.     

Effects of COMT genotype on behavioral symptomatology in the 22q11.2 Deletion Syndrome.

The 22q11.2 Deletion Syndrome (DiGeorge/velocardiofacial syndrome) is associated with elevated rates of psychosis, and is also characterized by severe attentional difficulties and executive dysfunction. Behavioral manifestations of this syndrome could result from haploinsufficiency of the catechol-O-methyltransferase (COMT) gene, located within the 22q11 region. The goal of the present study was to examine COMT genotype in relation to behavioral symptomatology in this syndrome. Val158/108Met was genotyped in 38 patients (16 Met/-, 22 Val/-) with confirmed 22q11.2 deletions who had received the Child Behavior Checklist (CBCL) as part of a comprehensive evaluation. Results indicated that the Val genotype was associated with significantly greater internalizing and externalizing behavioral symptomatology in children with 22q11.2 deletions. Val allele status was associated with a greater-than-four-fold increase in risk for clinically significant behavior problems in children with this syndrome. These data are consistent with previous findings of increased psychopathology associated with the Val genotype in normal individuals and suggest that a functional genetic polymorphism in the 22q11 region may influence behavior in individuals with COMT haploinsufficiency.     

Effects of Comt Genotype on Behavioral Symptomatology in the 22q11.2 Deletion Syndrome

The 22q11.2 Deletion Syndrome (DiGeorge/velocardiofacial syndrome) is associated with elevated rates of psychosis, and is also characterized by severe attentional difficulties and executive dysfunction. Behavioral manifestations of this syndrome could result from haploinsufficiency of the catechol-O-methyltransferase (COMT) gene, located within the 22q11 region. The goal of the present study was to examine COMT genotype in relation to behavioral symptomatology in this syndrome. Val^158/108Met was genotyped in 38 patients (16 Met/-, 22 Val/-) with confirmed 22q11.2 deletions who had received the Child Behavior Checklist (CBCL) as part of a comprehensive evaluation. Results indicated that the Val genotype was associated with significantly greater internalizing and externalizing behavioral symptomatology in children with 22q11.2 deletions. Val allele status was associated with a greater-than-four-fold increase in risk for clinically significant behavior problems in children with this syndrome. These data are consistent with previous findings of increased psychopathology associated with the Val genotype in normal individuals and suggest that a functional genetic polymorphism in the 22q11 region may influence behavior in individuals with COMT haploinsufficiency.