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。     

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。     

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。     

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。     

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。     

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。     

基因-大脑-行为框架下的抑制控制与老化

抑制控制能力是认知功能的重要成分。神经影像研究表明, 老年人抑制控制能力改变与前额叶皮层萎缩、神经元丧失有着密切关系, 抑制过程中前额叶需要以更高水平的激活达到代偿目的。遗传学研究表明, 抑制控制相关认知老化具有个体差异性, 大脑结构功能对个体差异的作用会出现衰退, 而遗传变异作用逐渐增加, 并使之成为认知老化个体差异性的主要原因之一。未来研究应利用遗传影像学, 结合影像学和遗传学优势, 在基因、大脑和行为框架下探索抑制控制与老化。     

科学发明情境中问题提出的fMRI研究

本研究中, 以76个科学发明问题(36个带有相关的原型, 40个不带有相关的原型)为实验材料,使用功能性磁共振成像(fMRI)技术探讨了科学发明情境中的问题提出以及新近获得的语义对有价值的科学问题提出的启发效应的大脑机制。对有原型提出有价值的科学问题与无原型提出一般问题这两种情况下被试反应的数据进行记录和分析。结果表明两种情况下共同激活的脑区(科学发明情境中问题提出的脑区)为左侧梭状回、左侧内侧额叶、左侧豆状核、右小脑和左侧中央前回。这些共同激活的脑区表明：左侧梭状回也许与各个语句的语义表征有关; 左侧内侧额叶也许与所有语句的整体语义表征以及提出各个语义之间的“问题”有关(左侧豆状核和右小脑配合内侧额叶分别负责控制注意、眼动的指向和注意资源的分配); 左侧中央前回可能负责用语句表述出所提出的语义之间的“问题”。对有原型提出有价值的科学问题和无原型提出有价值的科学问题这两种情况下被试反应的数据进行记录和分析。结果表明有原型提出有价值的科学问题比无原型提出有价值的科学问题显著激活的脑区(科学发明情境中新近获得的语义对有价值的科学问题提出的启发效应的脑区)为左侧楔前叶、左侧额下回、左侧颞中回。这些显著激活的脑区表明：楔前叶与情境记忆的贮存和提取有关; 额中回与认知控制和注意资源的分配有关; 颞中回与新异性原型的成功激活有关。     

科学发明情境中问题提出的fMRI研究*

本研究中,以76个科学发明问题(36个带有相关的原型,40个不带有相关的原型)为实验材料,使用功能性磁共振成像(fMRI)技术探讨了科学发明情境中的问题提出以及新近获得的语义对有价值的科学问题提出的启发效应的大脑机制。对有原型提出有价值的科学问题与无原型提出一般问题这两种情况下被试反应的数据进行记录和分析。结果表明两种情况下共同激活的脑区(科学发明情境中问题提出的脑区)为左侧梭状回、左侧内侧额叶、左侧豆状核、右小脑和左侧中央前回。这些共同激活的脑区表明：左侧梭状回也许与各个语句的语义表征有关;左侧内侧额叶也许与所有语句的整体语义表征以及提出各个语义之间的―问题‖有关(左侧豆状核和右小脑配合内侧额叶分别负责控制注意、眼动的指向和注意资源的分配);左侧中央前回可能负责用语句表述出所提出的语义之间的―问题‖。对有原型提出有价值的科学问题和无原型提出有价值的科学问题这两种情况下被试反应的数据进行记录和分析。结果表明有原型提出有价值的科学问题比无原型提出有价值的科学问题显著激活的脑区(科学发明情境中新近获得的语义对有价值的科学问题提出的启发效应的脑区)为左侧楔前叶、左侧额下回、左侧颞中回。这些显著激活的脑区表明：楔前叶与情境记忆的贮存和提取有关;额中回与认知控制和注意资源的分配有关;颞中回与新异性原型的成功激活有关。     

语言熟练度对Stroop效应的影响——不平衡双语者的任务态fMRI研究

目的:探讨语言熟练度对Stroop效应的影响及其背后的脑机制。材料与方法:17位被试参与本研究。被试母语为汉语,第二语言为英语。在被试完成中英文的stroop色字的任务过程中对被试进行fMRI扫描。结果:在色字相一致的条件下,中文任务与英文任务相比,双侧背侧枕叶及右侧背外侧前额叶有更强的激活; 反向比较,双侧腹侧枕叶有更强的激活。在色字不一致的条件下,中文任务与英文任务相比,双侧背外侧前额叶、右侧枕下回有更强的激活; 反向比较,并无显著激活的脑区。此外,中文Stroop效应引起左侧额下回显著的激活。英文Stroop效应中,左侧额下回无显著激活。结论:结合前人研究,我们得出,语言熟练度影响了对注意控制有重要作用的背外侧前额叶以及与反应抑制有关的左侧额下回在Stroop任务中的参与程度,进而影响了Stroop任务的表现     

多巴胺系统基因对注意网络的调控作用

多巴胺是脑内重要的神经递质之一,与注意活动紧密相关。本文选取作用于突触前膜、间隙和后膜的多巴胺系统基因——多巴胺转运蛋白基因、儿茶酚氧化甲基转移酶基因和多巴胺受体基因,整合影像遗传学研究,探讨多巴胺基因对注意网络的调控。元分析发现背侧和腹侧注意网络的主要脑区均有较大的基因调控效应,且腹侧网络的效应值显著大于背侧网络,表明多巴胺系统基因在全脑范围内调控注意网络,且对腹侧网络的调控作用更强于背侧网络。     

Effect of the COMT Val158Met genotype on lateral prefrontal activations in young children

Low executive function (EF) during early childhood is a major risk factor for developmental delay, academic failure, and social withdrawal. Susceptible genes may affect the molecular and biological mechanisms underpinning EF. More specifically, genes associated with the regulation of prefrontal dopamine may modulate the response of prefrontal neurons during executive control. Several studies with adults and older children have shown that variants of the catechol‐O‐methyltransferase (COMT) gene are associated with behavioral performance and prefrontal activations in EF tasks. However, the effect of the COMT genotype on prefrontal activations during EF tasks on young children is still unknown. The present study examined whether a common functional polymorphism (Val158Met) in the COMT gene was associated with prefrontal activations and cognitive shifting in 3‐ to 6‐year‐old children. The study revealed that, compared with children with at least one Met allele (Met/Met and Met/Val), children who were Val homozygous (i) were more able to flexibly switch rules in cognitive shifting tasks and (ii) exhibited increased activations in lateral prefrontal regions during these tasks. This is the first evidence that demonstrates the relationship between a gene polymorphism and prefrontal activations in young children. It also indicates that COMT Val homozygosity may be advantageous for cognitive shifting and prefrontal functions, at least during early childhood, and children who possess this variant may have a lower risk of developing future cognitive and social development issues.     

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.     

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.     

The negative consequences of threat: a functional magnetic resonance imaging investigation of the neural mechanisms underlying women's underperformance in math

This study used functional magnetic resonance imaging to identify the neural structures associated with women's underperformance on math tasks. Although women in a control condition recruited neural networks that are associated with mathematical learning (i.e., angular gyrus, left parietal and prefrontal cortex), women who were reminded of gender stereotypes about math ability did not recruit these regions, and instead revealed heightened activation in a neural region associated with social and emotional processing (ventral anterior cingulate cortex).     

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.