COMT Val158Met genotype is associated with reward learning: a replication study and meta‐analysis

Identifying mechanisms through which individual differences in reward learning emerge offers an opportunity to understand both a fundamental form of adaptive responding as well as etiological pathways through which aberrant reward learning may contribute to maladaptive behaviors and psychopathology. One candidate mechanism through which individual differences in reward learning may emerge is variability in dopaminergic reinforcement signaling. A common functional polymorphism within the catechol‐O‐methyl transferase gene (COMT; rs4680, Val¹⁵⁸Met) has been linked to reward learning, where homozygosity for the Met allele (linked to heightened prefrontal dopamine function and decreased dopamine synthesis in the midbrain) has been associated with relatively increased reward learning. Here, we used a probabilistic reward learning task to asses response bias, a behavioral form of reward learning, across three separate samples that were combined for analyses (age: 21.80 ± 3.95; n = 392; 268 female; European‐American: n = 208). We replicate prior reports that COMT rs4680 Met allele homozygosity is associated with increased reward learning in European‐American participants (β = 0.20, t = 2.75, P < 0.01; ΔR² = 0.04). Moreover, a meta‐analysis of 4 studies, including the current one, confirmed the association between COMT rs4680 genotype and reward learning (95% CI ?0.11 to ?0.03; z = 3.2; P < 0.01). These results suggest that variability in dopamine signaling associated with COMT rs4680 influences individual differences in reward which may potentially contribute to psychopathology characterized by reward dysfunction.     

The Effect of CYP19 and COMT Polymorphisms on Exercise‐Induced Fat Loss in Postmenopausal Women

Objective:To examine whether genetic polymorphisms in CYP19 [intron 4 (TTTA)_n; n = 7 to 13 and a 3‐base pair deletion, which is in strong linkage disequilibrium with the seven repeat] and COMT (Val^108/158Met) modified the change in BMI, total and percentage body fat, or subcutaneous and intra‐abdominal fat during a year‐long exercise intervention trial. These genes metabolize estrogens and androgens, which are important in body fat regulation. Research Methods and Procedures: A randomized intervention trial was used, with an intervention goal of 225 min/wk of moderate‐intensity exercise for one year. Participants (n = 173) were postmenopausal, 50 to 75 years old, sedentary, overweight or obese, and not taking hormone therapy at baseline. Results: Exercisers with two vs. no CYP19 11‐repeat alleles had a larger decrease in total fat (?3.1 kg vs. ?0.5 kg, respectively, p = 0.01) and percentage body fat (?2.4% vs. ?0.6%, respectively, p = 0.001). Exercisers with the COMT Met/Met vs. Val/Val genotype had a smaller decrease in percentage fat (?0.7% vs. ?1.9%, respectively, p = 0.05). Among exercisers, women with the COMT Val/Val genotype and at least one copy of the CYP19 11‐repeat allele vs. those with neither genotype/allele had a significantly larger decrease in BMI (?1.0 vs. +0.1 kg/m², respectively, p = 0.009), total fat (?2.9 vs. ?0.5 kg, respectively, p = 0.004), and percentage body fat (?2.6% vs. ?0.4%, respectively, p < 0.001). Discussion: Genetic polymorphisms in CYP19 and COMT may be important for body fat regulation and possibly modify the effect of exercise on fat loss in postmenopausal women.     

COMT val158met predicts reward responsiveness in humans

A functional variant of the catechol‐O‐methyltransferase (COMT) gene [val158met (rs4680)] is frequently implicated in decision‐making and higher cognitive functions. It may achieve its effects by modulating dopamine‐related decision‐making and reward‐guided behaviour. Here we demonstrate that individuals with the met/met polymorphism have greater responsiveness to reward than carriers of the val allele and that this correlates with risk‐seeking behaviour. We assessed performance on a reward responsiveness task and the Balloon analogue risk task, which measure how participants (N = 70, western European, university and postgraduate students) respond to reward and take risks in the presence of available reward. Individuals with the met/met genotype (n = 19) showed significantly higher reward responsiveness, F_2,64 = 4.02, P = 0.02, and reward‐seeking behaviour, F(2,68) = 4.52, P = 0.01, than did either val/met (n = 25) or val/val (n = 26) carriers. These results highlight a scenario in which genotype‐dependent reward responsiveness shapes reward‐seeking, therefore suggesting a novel framework by which COMT may modulate behaviour.     

COMT but not serotonin‐related genes modulates the influence of childhood abuse on anger traits

Anger‐related traits are regulated by genes as well as early environmental factors. Both childhood maltreatment and genes underlie vulnerability to suicidal behaviors, possibly by affecting the constitution of intermediate phenotypes such as anger traits. The aim of this study was to test the interaction between nine candidate genes and childhood maltreatment in modulating anger‐related traits in 875 adult suicide attempters. The State‐Trait Anger Expression Inventory and the Childhood Trauma Questionnaire were used to examine anger traits and traumatic childhood experiences, respectively. The functional polymorphism of the catecholamine‐O‐methyl‐transferase (COMT) gene Val158Met significantly modulated the association between sexual abuse and anger‐trait level (P = 0.001). In the presence of sexual abuse, individuals carrying the Val high‐activity allele displayed greater disposition toward anger than individuals homozygous for the Met allele (P = 0.0003). Notably, none of the serotonin‐related genes influenced the effect of childhood abuse on anger traits. The results of the present study suggest that anger‐trait level is influenced by the interaction between childhood abuse and functional polymorphism in the COMT gene. This study was carried out in a population with a high frequency of childhood abuse and a high disposition toward anger, and replication in healthy subjects is needed.     

COMT Val158Met moderates the link between rank and aggression in a non‐human primate

The COMT Val¹⁵⁸Met polymorphism is one of the most widely studied genetic polymorphisms in humans implicated in aggression and the moderation of stressful life event effects. We screened a wild primate population for polymorphisms at the COMT Val¹⁵⁸Met site and phenotyped them for aggression to test whether the human polymorphism exists and is associated with variation in aggressive behavior. Subjects were all adults from 4 study groups (37 males, 40 females) of Assamese macaques (Macaca assamensis) in their natural habitat (Phu Khieo Wildlife Sanctuary, Thailand). We collected focal animal behavioral data (27 males, 36 females, 5964 focal hours) and fecal samples for non‐invasive DNA analysis. We identified the human COMT Val¹⁵⁸Met polymorphism (14 Met/Met, 41 Val/Met and 22 Val/Val). Preliminary results suggest that COMT genotype and dominance rank interact to influence aggression rates. Aggression rates increased with rank in Val/Val, but decreased in Met/Met and Val/Met individuals, with no significant main effect of COMT genotype on aggression. Further support for the interaction effect comes from time series analyses revealing that when changing from lower to higher rank position Val/Val individuals decreased, whereas Met/Met individuals increased their aggression rate. Contradicting the interpretation of earlier studies, we show that the widely studied Val¹⁵⁸Met polymorphism in COMT is not unique to humans and yields similar behavioral phenotypes in a non‐human primate. This study represents an important step towards understanding individual variation in aggression in a wild primate population and may inform human behavioral geneticists about the evolutionary roots of inter‐individual variation in aggression.     

The divergent impact of COMT Val158Met on executive function in children with and without attention‐deficit/hyperactivity disorder

Children with attention‐deficit/hyperactivity disorder (ADHD) usually display deficits in executive function (EF), which are primarily mediated by prefrontal cortex (PFC). The functional polymorphism of catechol‐O‐methyltransferase (COMT), Val158Met (rs4680), leads to observed polymorphic differences in the degradation of dopamine within PFC. This study aimed to explore the effect of rs4680 on EF using case–control design. In addition, considering the dynamic development of EF, we also attempted to investigate whether this genetic influence changes during development or not. A total of 597 ADHD children and 154 unaffected controls were recruited. The EF was evaluated using Rey–Osterrieth complex figure test (RCFT), trail making test (TMT) and Stroop color and word test for working memory, shifting and inhibition. Association between genotype and EF was analyzed using analysis of covariance (ancova ). The results showed significant interaction effect of genotype and ADHD diagnosis on RCFT performance (P < 0.001). However, the associated genotypes between ADHD and controls were divergent. In ADHD, the Met carriers performed better than the Val homozygotes on detail immediate [(10.38 ± 6.90) vs. (9.33 ± 6.92), P = 0.007] and detail delay [(9.96 ± 6.86) vs. (8.86 ± 6.89), P = 0.004], while Val homozygotes showed better performance compared with Met carrier controls [for detail immediate (14.55 ± 6.18) vs. (11.10 ± 6.45), P<0.001; for detail delay (14.31 ± 5.96) vs. (11.31 ± 6.96), P = 0.001]. We did not find significant interaction between genetic variant and development. COMT Val158Met (rs4680) may have divergent effect on working memory in ADHD children compared with healthy controls.     

Association between maternal COMT gene polymorphisms and fetal neural tube defects risk in a Chinese population

Maternal tea consumption was reported to increase the risk of fetal neural tube defects (NTDs). Catechol‐O‐methyltransferase (COMT) may be involved in the metabolism of polyphenolic methylation of tea, thus influence the risk of fetal NTDs. Methods: A total of 576 fetuses or newborns with NTDs and 594 healthy newborns were included in the case–control study. Information on maternal tea consumption, sociodemographic characteristics, reproductive history, and related behavior was collected through face‐to‐face interviews. Maternal blood samples were collected to examine polymorphisms in COMT, and the possible interaction of COMT and tea consumption was analyzed. RESULTS: After controlling for potential confounders, homozygotes of rs737865 showed an elevated risk for total NTDs (odds ratio [OR] = 2.04, 95% confidence interval [CI], 1.24–3.35) and for the anencephaly subtype (OR = 1.99, 95% CI, 1.17–3.39). The CC genotype of rs4633 was positively associated with the overall risk of NTDs (OR = 3.66, 95% CI, 1.05–12.83). Heterozygotes for rs4680 were associated with a decreased risk of spina bifida (OR = 0.71, 95% CI, 0.51–0.98). The COMT rs4680 A allele was negatively related with the risk of spina bifida, with adjusted OR = 0.64 (95% CI, 0.45–0.89). An interaction between tea consumption (1 to 2 cups/day) and the rs4680AA/AG genotype was found in the spina bifida subtype (P_interaction = .08). Conclusion: Several COMT variants were associated with elevated risk of NTDs in a Chinese population. Maternal tea consumption may be associated with an increased risk for fetal NTDs in genetically susceptible subgroups. Birth Defects Research (Part A) 100:22–29, 2014. © 2013 Wiley Periodicals, Inc.     

Association of BDNF and COMT genotypes with cognitive processing of anti-smoking PSAs

Anti-smoking public service announcements (PSAs) often use persuasive arguments to attempt to influence attitudes about smoking. The persuasiveness of a PSA has previously been associated with factors that influence the cognitive processing of its message. Genetic factors that influence cognitive processing might thus affect individuals' responses to the persuasive arguments presented in PSAs. In the present study, we examined polymorphisms in the genes encoding brain-derived neurotrophic factor (BDNF Val66Met) and catechol-O-methyltransferase (COMT Val158Met), which affect cognitive processing in the prefrontal cortex, to identify genetic factors associated with self-reported outcomes of message processing, perceived effectiveness and quitting intentions among smokers viewing PSAs. A total of 120 smokers viewed sets of four PSAs that varied with respect to features of argument strength (AS) and message sensation value. We observed significant associations of BDNF genotype with central processing, narrative processing, perceived effectiveness of the anti-smoking PSAs and participant quitting intentions; the BDNF Met allele was associated with lower scores on all these measures. Central processing acted as a mediator of the association of genotype with quitting intentions and perceived effectiveness. There was a significant interaction of COMT genotype by AS in the model of narrative processing, such that individuals homozygous for the COMT Val allele reported higher narrative processing in the high-AS condition but not in the low-AS condition. To our knowledge, this is the first study to identify genetic factors associated with cognitive processing of anti-smoking PSAs.     

The molecular genetics of cognition: dopamine, COMT and BDNF

The important contribution of genetic factors to the development of cognition and intelligence is widely acknowledged, but identification of these genes has proven to be difficult. Given a variety of evidence implicating the prefrontal cortex and its dopaminergic circuits in cognition, most of the research conducted to date has focused on genes regulating dopaminergic function. Here we review the genetic association studies carried out on catechol-O-methyltransferase (COMT) and the dopamine receptor genes, D1, D2 and D4. In addition, the evidence implicating another promising candidate gene, brain-derived neurotrophic factor (BDNF) in neuropsychological function, is assessed. Both the COMT val158met polymorphism and the BDNF val66met variant appear to influence cognitive function, but the specific neurocognitive processes involved continue to be a matter of debate. Part of the difficulty is distinguishing between false positives, pleiotropy and the influence of a general intelligence factor, g. Also at issue is the complexity of the relevant neuromolecular pathways, which make the inference of simple causal relationships difficult. The implications of molecular genetic cognitive research for psychiatry are discussed in light of these data.     

The interaction of early life experiences with COMT val158met affects anxiety sensitivity

The pathogenesis of anxiety disorders is considered to be multifactorial with a complex interaction of genetic factors and individual environmental factors. Therefore, the aim of this study was to examine gene‐by‐environment interactions of the genes coding for catechol‐O‐methyltransferase (COMT) and monoamine oxidase A (MAOA) with life events on measures related to anxiety. A sample of healthy subjects (N = 782; thereof 531 women; mean age M = 24.79, SD = 6.02) was genotyped for COMT rs4680 and MAOA‐uVNTR (upstream variable number of tandem repeats), and was assessed for childhood adversities [Childhood Trauma Questionnaire (CTQ)], anxiety sensitivity [Anxiety Sensitivity Index (ASI)] and anxious apprehension [Penn State Worry Questionnaire (PSWQ)]. Main and interaction effects of genotype, environment and gender on measures related to anxiety were assessed by means of regression analyses. Association analysis showed no main gene effect on either questionnaire score. A significant interactive effect of childhood adversities and COMT genotype was observed: Homozygosity for the low‐active met allele and high CTQ scores was associated with a significant increment of explained ASI variance [R² = 0.040, false discovery rate (FDR) corrected P = 0.04]. A borderline interactive effect with respect to MAOA‐uVNTR was restricted to the male subgroup. Carriers of the low‐active MAOA allele who reported more aversive experiences in childhood exhibited a trend for enhanced anxious apprehension (R² = 0.077, FDR corrected P = 0.10). Early aversive life experiences therefore might increase the vulnerability to anxiety disorders in the presence of homozygosity for the COMT 158met allele or low‐active MAOA‐uVNTR alleles .     

Differential expression and activity of catechol-O-methyl transferase (COMT) in a generalist (Neotoma albigula) and juniper specialist (Neotoma stephensi) woodrat

Mammalian herbivores, particularly dietary specialists must have an efficient means to metabolize the high doses of plant secondary compounds they consume. We found previously that Neotoma stephensi, a juniper specialist, upregulated catechol-O-methyl transferase (COMT) mRNA almost seven fold in response to an ecologically relevant diet (70% juniper). To further investigate the relevance of this enzyme with respect to juniper metabolism, we compared the protein expression, activity and kinetics of the two forms of COMT, soluble (S-COMT) and membrane bound (MB-COMT), in the blood, kidneys and liver of N. stephensi on its natural juniper diet to that of N. stephensi fed an experimental diet of 70% juniper as well as a non-toxic control diet under laboratory conditions. In addition, we compared these results to that of Neotoma albigula, a generalist species, which consumes a diet of 25% juniper in the wild. The specialist consuming juniper under both field and laboratory conditions had increased S-COMT expression and activity in their livers and kidneys, and increased S-COMT activity in their blood compared to the specialist and generalist fed the control diet. The specialist showed expression and activity of S-COMT in their kidneys that was as high as or higher than that in their livers. The generalist had an elevated V_max for MB-COMT compared to the specialist that resulted in higher activity for MB-COMT than the specialist despite lower expression of MB-COMT in the generalist's livers and kidneys. This high activity MB-COMT may be in part responsible for differences in the behaviors of the generalist compared to the specialist. We conclude that S-COMT is important in the specialist's ability to consume high levels of juniper.     

RNAi‐suppression of barley caffeic acid O‐methyltransferase modifies lignin despite redundancy in the gene family

Caffeic acid O‐methyltransferase (COMT), the lignin biosynthesis gene modified in many brown‐midrib high‐digestibility mutants of maize and sorghum, was targeted for downregulation in the small grain temperate cereal, barley (Hordeum vulgare), to improve straw properties. Phylogenetic and expression analyses identified the barley COMT orthologue(s) expressed in stems, defining a larger gene family than in brachypodium or rice with three COMT genes expressed in lignifying tissues. RNAi significantly reduced stem COMT protein and enzyme activity, and modestly reduced stem lignin content while dramatically changing lignin structure. Lignin syringyl‐to‐guaiacyl ratio was reduced by ~50%, the 5‐hydroxyguaiacyl (5‐OH‐G) unit incorporated into lignin at 10‐–15‐fold higher levels than normal, and the amount of p‐coumaric acid ester‐linked to cell walls was reduced by ~50%. No brown‐midrib phenotype was observed in any RNAi line despite significant COMT suppression and altered lignin. The novel COMT gene family structure in barley highlights the dynamic nature of grass genomes. Redundancy in barley COMTs may explain the absence of brown‐midrib mutants in barley and wheat. The barley COMT RNAi lines nevertheless have the potential to be exploited for bioenergy applications and as animal feed.     

COMT polymorphism modulates the resting‐state EEG alpha oscillatory response to acute nicotine in male non‐smokers

Performance improvements in cognitive tasks requiring executive functions are evident with nicotinic acetylcholine receptor (nAChR) agonists, and activation of the underlying neural circuitry supporting these cognitive effects is thought to involve dopamine neurotransmission. As individual difference in response to nicotine may be related to a functional polymorphism in the gene encoding catechol‐O‐methyltransferase (COMT), an enzyme that strongly influences cortical dopamine metabolism, this study examined the modulatory effects of the COMT Val158Met polymorphism on the neural response to acute nicotine as measured with resting‐state electroencephalographic (EEG) oscillations. In a sample of 62 healthy non‐smoking adult males, a single dose (6 mg) of nicotine gum administered in a randomized, double‐blind, placebo‐controlled design was shown to affect α oscillatory activity, increasing power of upper α oscillations in frontocentral regions of Met/Met homozygotes and in parietal/occipital regions of Val/Met heterozygotes. Peak α frequency was also found to be faster with nicotine (vs. placebo) treatment in Val/Met heterozygotes, who exhibited a slower α frequency compared to Val/Val homozygotes. The data tentatively suggest that interindividual differences in brain α oscillations and their response to nicotinic agonist treatment are influenced by genetic mechanisms involving COMT.     

COMT基因多态性与儿童精神发育迟滞及儿童认知能力的相关性研究

儿茶酚-O-甲基转移酶（catechol-O-methyl transferase,COMT）是儿茶酚胺类神经递质的主要代谢酶.COMT是儿茶酚-O-甲基转移酶的编码基因,其第4外显子的一个G/A转换可产生不同活性的等位基因.许多遗传学研究报道,这种功能多态性与人类精神类疾病相关.文章利用PCR扩增技术和限制性片段长度多态（Restriction fragmentlength polymorphism,RFLP）方法,研究中国秦巴山区精神发育迟滞（Mental Retardation,MR）儿童与正常对照儿童的COMT基因功能多态情况,探讨COMT基因功能多态性与儿童认知能力水平的相关性.病例-对照分析结果显示,COMT基因的不同活性等位基因型与秦巴山区儿童MR无相关性（x2=0.776,P＞0.05）,其等位基因频率与儿童MR也未呈现出相关性（x2=0.335,P＞0.05）.但是,在研究中还发现,该地区智商分（IQ）不小于55分的儿童群体中,COMT基因的多态性分布与儿童的智力呈现出相关的趋势.在智力正常组儿童中（IQ≥85）,COMT高活性等位基因纯合体（COMTHH）频率及其等位基因（COMTH）频率较高,分别为60.98%、79.28%.在智力边缘组儿童（70≤IQ＜85）中,其频率分别为46.67%、70.67%,相应地也低于正常组的频率（0.10＞P＞0.05）.结果提示,在中国秦巴山区人群中,COMT基因的功能多态性与儿童MR的形成无明显相关性,但它对正常儿童的认知能力可能有一定影响.     

Clinical pharmacology of the new COMT inhibitor CGP 28 014

CGP 28 014 is a specific inhibitor of catechol-O-methyltransferase (COMT) in vivo. In humans, the inhibition was assessed by measuring urinary excretion of isoquinolines and with the levodopa test. Following administration of CGP 28 014, urinary excretion of isoquinolines was significantly increased. In rats, CGP 28 014 reduced plasma and striatal concentrations of 3-O-methyldopa (30MD) in a dose-dependent manner. Acute and subchronic administration of CGP 28 014 alone or in combination with the peripherally acting decarboxylase inhibitor benserazide decreased plasma 30MD as an index of COMT inhibition by about 50%. There seems to be a close relationship between the time-course of plasma concentrations of CGP 28 014 and the extent of COMT inhibition assessed by the 30MD/DOPA ratio in plasma.     

Catechol‐O‐methyltransferase gene methylation and substance use in adolescents: the TRAILS study

Substance use often starts in adolescence and poses a major problem for society and individual health. The dopamine system plays a role in substance use, and catechol‐O‐methyltransferase (COMT) is an important enzyme that degrades dopamine. The Val^108/158Met polymorphism modulates COMT activity and thus dopamine levels, and has been linked to substance use. COMT gene methylation, on the other hand, may affect expression and thus indirectly COMT activity. We investigated whether methylation of the COMT gene was associated with adolescents' substance use. Furthermore, we explored whether the COMT Val^108/158Met polymorphism interacts with COMT gene methylation in association with substance use. In 463 adolescents (mean age = 16, 50.8% girls), substance use (cigarette smoking, alcohol and cannabis use) was assessed with self‐report questionnaires. From blood samples, COMT Val^108/158Met genotype and methylation rates of membrane bound (MB) and soluble (S) COMT promoters were assessed. MB‐COMT promoter methylation was associated with non‐daily smoking [odds ratio (OR) = 1.82, P = 0.03], but not with daily smoking (OR = 1.20, P = 0.34), MB‐COMT promoter methylation was not associated with alcohol use. Adolescents with the Met/Met genotype and high rates of MB‐COMT promoter methylation were less likely to be high‐frequent cannabis users than adolescents with the Val/Val or Val/Met genotype. S‐COMT promoter methylation was not associated with substance use. These results indicate that there is an association between substance use and COMT gene methylation. Although this association is complex, combining genetic and epigenetic variation of the COMT gene may be helpful in further elucidating the influence of the dopamine system on substance use in adolescence.     

COMT Val158Met and cognition: main effects and interaction with educational attainment

Studies in children have shown that the genetic influence on cognition is positively correlated with socioeconomic status. Catechol- O -methyltransferase (COMT) Val158Met, a common, functional polymorphism, has been implicated in executive cognition and working memory. Imaging studies have shown that the variant Met allele is associated with more efficient prefrontal cortical processing and better attention but also emotional vulnerability to stress. We hypothesized that COMT Val158Met genotype would interact with years of education (yrs ed), one indicator of socioeconomic adversity, to predict cognitive task performance. We therefore administered the Wechsler Adult Intelligence Scale-Revised (WAIS-R) to 328 community-derived, genotyped, Plains American Indians (mean yrs ed = 12; range = 5–18). We found significant genotypic effects on WAIS-R measures of long-term memory, working memory and attention. The Met allele was associated with improved performance in the Information and Picture Completion subscales; Met/Met homozygotes performed the best. COMT genotype interacted with yrs ed to influence Information and Block Design scores: Met allele carriers' scores improved markedly with increasing yrs ed, whereas the scores of Val/Val individuals were only marginally influenced by yrs ed. There was a crossover of effects at 11–12 yrs ed: in the less educated group, Met allele carriers actually performed worse than Val/Val individuals perhaps because of emotional vulnerability to educational adversity, but in the better educated group, Met allele carriers excelled. Our study in Plains American Indians has shown that COMT Val158Met influences several aspects of cognition and some of its effects are moderated by educational adversity.     

The Associations between COMT and MAO-B Genetic Variants with Negative Symptoms in Patients with Schizophrenia

Negative symptoms of schizophrenia, including anhedonia, represent a heavy burden on patients and their relatives. These symptoms are associated with cortical hypodopamynergia and impaired striatal dopamine release in response to reward stimuli. Catechol-O-methyltransferase (COMT) and monoamine oxidase type B (MAO-B) degrade dopamine and affect its neurotransmission. The study determined the association between COMT rs4680 and rs4818, MAO-B rs1799836 and rs6651806 polymorphisms, the severity of negative symptoms, and physical and social anhedonia in schizophrenia. Sex-dependent associations were detected in a research sample of 302 patients with schizophrenia. In female patients with schizophrenia, the presence of the G allele or GG genotype of COMT rs4680 and rs4818, as well as GG haplotype rs4818-rs4680, which were all related to higher COMT activity, was associated with an increase in several dimensions of negative symptoms and anhedonia. In male patients with schizophrenia, carriers of the MAO-B rs1799836 A allele, presumably associated with higher MAO-B activity, had a higher severity of alogia, while carriers of the A allele of the MAO-B rs6651806 had a higher severity of negative symptoms. These findings suggest that higher dopamine degradation, associated with COMT and MAO-B genetic variants, is associated with a sex-specific increase in the severity of negative symptoms in schizophrenia patients.     

COMT Val158Met多态型青年在数字工作记忆任务中的视觉事件相关电位的研究

目的:针对不同COMT基因型健康青年被试,进行连续3-back任务1h共12Block,探讨健康成人数字工作记忆能力变化情况。方法:将112名健康青年分组抽取出18名不同基因型作为被试,利用视觉事件相关电位P3来观测被试连续工作记忆任务中COMT基因多态型与脑皮层电生理的关系。结果:Val/Val基因型的被试P3波幅显著高于Val/Met基因型(P<0.01),但和Met/Met基因型被试的波幅无差异。结论:Val/Met基因型被试关联着最差的工作记忆任务的成绩,被试者的P3波幅和3-back任务成绩成正相关。     

Sex effects for the interaction of dopamine related genetic variants for COMT and BDNF on declarative memory performance

Genetic factors are assumed to contribute to memory performance, especially genes affecting the dopaminergic neurotransmission. We aimed to evaluate leading functional genetic variants of the dopamine system, Catechol-O-methyltransferase (COMT) SNP rs4680 and Brain-derived neurotropic factor (BDNF) SNP rs6265, previously found to be associated with memory performance. In two independent general population cohorts (total N = 5937) we investigated direct and interaction effects between COMT and BDNF SNPs on declarative memory performance. We found significant two-way interactions for COMT and BDNF in both cohorts but no direct genetic effects. Sensitivity analyses revealed that an interaction between COMT and BDNF was mainly carried by females. While direct associations of COMT and BDNF on memory have been reported previously, we could demonstrate that the interaction of COMT and BDNF is sex-dependent and more complex and needs further investigation. Our results could be demonstrated in two independent cohorts of valuable size.