The "Warrior" COMT Val/Met Genotype Occurs in Greater Frequencies in Mixed Martial Arts Fighters Relative to Controls.

A functional single-nucleotide polymorphism (SNP) in the catechol-O-methyltransferase (COMT) gene (rs4680) is a gene variant that has been shown to predict the ability to maintain cognitive agility during combat and competition. Critically, COMT Met (low-activity; high dopamine) allele carriers outperform Val (high-activity; low dopamine) homozygotes on a variety of cognitive tasks. However, the relationship between genotype and cognitive performance appears to reverse under stressful conditions. Stress increases pre-frontal cortex dopamine (PFC DA) levels, and Met allele carriers (with higher DA) show performance deficits relative to Val allele carriers. This pattern reflects the inverted U-shaped function of DA activity where too little (Val allele) or too much (Met allele carriers under stress) DA is associated with poor cognitive performance. The Val allele advantage for stress resiliency is referred to as the COMT "warrior/ worrier" model. In line with this model, we predicted that elite level mixed martial arts (MMA) fighters would be more likely than athlete controls to carry the GG (warrior) genotype compared to an athlete group and a non-athlete group. Based on findings in our previous studies, we also assessed the stress biomarkers cortisol and salivary alpha-amylase (sAA). There was an overall significant difference in genotype frequencies between groups (p =0.01) and the MMA group showed a significantly greater GG (warrior) genotype frequency than the non-athlete control group (p = 0.003). There was not a significant group x genotype interaction for the cortisol or sAA; however, the non-athlete GG group had significantly higher cortisol than the A/- group (p = 0.038). Combined, our findings suggest that the "warrior" genotype may play a participation role in combat sports.

COMT Genotype and Sensory and Sensorimotor Gating in High and Low Hypnotizable Subjects.

We investigated the association between hypnotizability, COMT polymorphism, P50 suppression ratio, and prepulse inhibition of acoustic startle response (ASR) in 21 high (HH) and 19 low (LH) hypnotizable subjects. The frequency of Met/Met carriers of COMT polymorphysm was higher in HH than in LH group (33.3% versus 10.6%, p = .049). Increased ASR amplitude and latency and decreased prepulse inhibition at 120 ms lead interval were found in the HH compared to the LH group. The effect of COMT genotype on prepulse inhibition was observed in LH group only. No between-group differences in P50 measures were found. The obtained results suppose the participation of dopamine system in mechanisms of hypnotizability and different allocation of attentional resources in HH and LH subjects.

COMT and DRD2/ANKK-1 gene-gene interaction account for resetting of gamma neural oscillations to auditory stimulus-driven attention.

Attention capture by potentially relevant environmental stimuli is critical for human survival, yet it varies considerably among individuals. A large series of studies has suggested that attention capture may depend on the cognitive balance between maintenance and manipulation of mental representations and the flexible switch between goal-directed representations and potentially relevant stimuli outside the focus of attention; a balance that seems modulated by a prefrontostriatal dopamine pathway. Here, we examined inter-individual differences in the cognitive control of attention through studying the effects of two single nucleotide polymorphisms regulating dopamine at the prefrontal cortex and the striatum (i.e., COMTMet108/158Val and ANKK1/DRD2TaqIA) on stimulus-driven attention capture. Healthy adult participants (N = 40) were assigned to different groups according to the combination of the polymorphisms COMTMet108/158Val and ANKK1/DRD2TaqIA, and were instructed to perform on a well-established distraction protocol. Performance in individuals with a balance between prefrontal dopamine display and striatal receptor density was slowed down by the occurrence of unexpected distracting events, while those with a rather unbalanced dopamine activity were able maintain task performance with no time delay, yet at the expense of a slightly lower accuracy. This advantage, associated to their distinct genetic profiles, was paralleled by an electrophysiological mechanism of phase-resetting of gamma neural oscillation to the novel, distracting events. Taken together, the current results suggest that the epistatic interaction between COMTVal108/158Met and ANKK1/DRD2 TaqIa genetic polymorphisms lies at the basis of stimulus-driven attention capture.

Carriers of the COMT Met/Met allele have higher degrees of hypnotizability, provided that they have good attentional control: a case of gene-trait interaction.

Genetic factors may explain part of the interindividual variability in hypnotizability. A new avenue that may provide more comprehensive understanding of the phenotypic effects of genetic variations is the study of gene-trait interaction. In this study, the authors investigate the relationship of the dopamine-related COMT and the serotonin-related 5-HTTLPR polymorphisms to hypnotizability by taking individual differences in executive attention into account. Homozygosity for the COMT Met allele, putatively linked to the capability or proneness to dissociate from reality, was associated with high hypnotizability only if paired with high-attention ability. The finding can be integrated into hypnosis theory and represents a case of gene-trait interaction suggesting that investigating the effects of a gene in the context of relevant psychological traits may further elucidate gene-brain-behavior relationships.

Functional brain networks underlying perceptual switching: auditory streaming and verbal transformations.

Recent studies have shown that auditory scene analysis involves distributed neural sites below, in, and beyond the auditory cortex (AC). However, it remains unclear what role each site plays and how they interact in the formation and selection of auditory percepts. We addressed this issue through perceptual multistability phenomena, namely, spontaneous perceptual switching in auditory streaming (AS) for a sequence of repeated triplet tones, and perceptual changes for a repeated word, known as verbal transformations (VTs). An event-related fMRI analysis revealed brain activity timelocked to perceptual switching in the cerebellum for AS, in frontal areas for VT, and the AC and thalamus for both. The results suggest that motor-based prediction, produced by neural networks outside the auditory system, plays essential roles in the segmentation of acoustic sequences both in AS and VT. The frequency of perceptual switching was determined by a balance between the activation of two sites, which are proposed to be involved in exploring novel perceptual organization and stabilizing current perceptual organization. The effect of the gene polymorphism of catechol-O-methyltransferase (COMT) on individual variations in switching frequency suggests that the balance of exploration and stabilization is modulated by catecholamines such as dopamine and noradrenalin. These mechanisms would support the noteworthy flexibility of auditory scene analysis.

Catechol-O-methyltransferase polymorphisms do not play a significant role in pain perception in male Chinese Han population.

Polymorphisms in the human catechol-O-methyltransferase (COMT) gene have been widely studied for their role in pain and analgesia. In this study, sensitivity to potassium iontophoresis, visual analog scale measurements for fixed twofold pain threshold stimulation and pain threshold changes induced by transcutaneous electrical acupoint stimulation (TEAS) were assessed in a population of healthy Chinese males. These results were correlated with the alleles of six single nucleotide polymorphisms (SNP) or diplotypes of common haplotypes designated as low pain sensitive, average pain sensitive, and high pain sensitive in the COMT gene of these subjects. Our results reveal that the alleles of each SNP are not significantly correlated with pain perception except for the rs4633 allele in the 2 Hz TEAS session (P < 0.05). In addition, the six diplotypes of COMT haplotypes, which cover 92.5% of the Chinese population, are also not correlated with pain perception. Moreover, there were no significant differences in pain threshold changes induced by 2 and 100 Hz TEAS among the diplotypes of each SNP or the various haplotypes. These results suggest that COMT activity do not play a significant role in pain perception and TEAS-induced analgesia in the Chinese Han male population.

Inhibition of catechol-Omicron-methyltransferase activity in human breast cancer cells enhances the biological effect of the green tea polyphenol (-)-EGCG.

Tea is one of the most popular beverages in the world and has been studied extensively as a health-promoting beverage that may act to prevent a number of chronic diseases and cancers. (-)-Epigallocatechin gallate [(-)-EGCG], a major component in green tea, is unstable under physiological conditions and methylation of (-)-EGCG by catechol-Omicron-methyltransferase (COMT) is a modification that reduces the biological activity of (-)-EGCG. In the current study, we hypothesized that suppression of COMT activity in human breast cancer cells could increase the proteasome-inhibitory potency of (-)-EGCG and therefore enhance its tumor cell growth-inhibitory activity. We first determined the COMT genotype and basal levels of COMT activity in various human breast cancer cell lines. Furthermore, when breast cancer MDA-MB-231 cells containing high COMT activity were tested, the diminished COMT activity apparently increased the effectiveness of (-)-EGCG via augmented proteasome inhibition and apoptosis induction. This study supplements the previous findings that methylated (-)-EGCG is less bioactive and supports the notion that COMT inhibition may increase the anti-cancer properties of tea polyphenols and the combination may serve as a novel approach or supplemental treatment for breast cancer chemotherapy.

Association between hypnotizability and the catechol-O-methyltransferase (COMT) polymorphism.

Previous studies implicate involvement of dopaminergic systems in hypnotizability and report association with the COMT Val(158)Met single nucleotide polymorphism (SNP, rs4680) demonstrating the Val/Met heterozygotes as the most hypnotizable group using the Stanford Hypnotic Susceptibility Scale. This study replicates that association using an independent sample of 127 healthy Hungarian young adults and the Waterloo-Stanford Group C Scale of Hypnotic Susceptibility. Significant association (p = .016) was found between the COMT genotypes and hypnotizability, with a clear additive effect of the Val allele: Hypnotizability scores were highest in Val/Val (5.9), intermediate in Val/Met (4.7), and lowest in Met/Met (4.1). Differences between these results and those of previous studies support recent findings suggesting an inverted-U-shaped relation between dopamine level in the prefrontal cortex and cognitive functioning. The present study replicates association of COMT Val(158)Met SNP and hypnotizability and stresses the importance of mediating factors, such as group vs. individual inductions.

Separation methods for catechol O-methyltransferase activity assay: physiological and pathophysiological relevance.

Catechol O-methyltransferase (COMT) transfers a methyl group from S-adenosyl-L-methionine to the catechol substrate in the presence of magnesium. After the characterisation of COMT more than four decades ago, a wide variety of COMT enzyme assays have been introduced. COMT activity analysis usually consists of the handling of the sample and incubation followed by separation and detection of the reaction products. Several of these assays are validated, reliable and sensitive. Besides the studies of the basic properties of COMT, the activity assay has also been applied to explore the relation of COMT to various disease states or disorders. In addition, COMT activity analysis has been applied clinically since COMT inhibitors have been introduced as adjuvant drugs in the treatment of Parkinson's disease.