Association of monoaminergic gene polymorphisms in chronic inflammatory pulmonary disease patients with successful smoking cessation.

BACKGROUND: Albeit smoking cessation has unequivocal health benefits, attempts to quit are not unanimous, even in patient populations at high risk for smoking-related diseases cessation. Allelic variations of enzymes involved in dopamine metabolism are being considered as candidates for nicotine addiction. We set out to assess whether rs4680 G/A and rs2235186 G/A polymorphisms of COMT and MAO-A, respectively are associated with the ability to quit smoking in chronic inflammatory pulmonary disease patients. METHODS: Patients managed for chronic inflammatory pulmonary disease by the Department of Pulmonology (University of Debrecen, Hungary), with a current or past smoking habit were included in the current analysis. The study was designed in line with the STROBE statement for cross-sectional studies and was approved by the National Center for Public Health, Hungary. Genomic DNA was extracted from peripheral blood specimens. SNPs were genotyped using TaqMan SNP genotyping assays. RESULTS: rs4680 COMT polymorphism showed significant effect for successful smoking cessation in patients with pulmonary disease. Accordingly, A/A subjects had lower odds for successful smoking cessation (odds ratio 0.37; 95% confidence interval 0.20-0.69, p = 0.002 (additive model). On the other hand, patients homozygous for the minor allele (A) at rs2235186 of MAO-A showed a non-significant trend toward increased odds for successful smoking cessation. CONCLUSIONS: The presence of the minor allele for rs4680 COMT was shown to decrease the odds for successful smoking cessation, a finding that may be interpreted in view of the altered balance between tonic and phasic dopamine release.

Pain-related single nucleotide polymorphisms: association with lumbar spinal stenosis patient experience and non-surgical treatment outcomes.

PURPOSE: Lumbar spinal stenosis (LSS) is common in our aging population resulting in pain and functional impairment. Recent advances in pain research have identified several single nucleotide polymorphisms (SNP) associated with inter-individual symptom and treatment response. The goal of the current study was to investigate the association of SNPs in Neuropeptide Y (NPY) and Catechol-O-methyltransferase (COMT) with pain, function, and treatment outcomes in Lumbar spinal stenosis (LSS) patients receiving non-surgical treatments. METHODS: An exploratory observational biomarker study was performed ancillary to a previously published clinical trial evaluating three different non-surgical treatments for LSS. Saliva samples were obtained for single nucleotide polymorphism genotyping and blood samples were collected for NPY protein. Data on pain and function collected as part of the clinical trial at baseline, 2 and 6 months were examined for association with known polymorphisms in NPY and COMT. RESULTS: Subjects with the NPY rs16147 TT genotype exhibited higher baseline symptom severity but also a higher likelihood of responding to non-surgical treatments. Subjects with the COMT rs4680 GG genotype also exhibited higher baseline symptom severity but did not demonstrate greater response to treatment. CONCLUSIONS: NPY rs16147 and COMT rs4680 are important potential biomarkers associated with pain and function. NPY genotype may be useful in predicting response to non-surgical treatments in older adults with LSS.

The Influence of Genetic Polymorphic Variability of the Catechol-O-methyltransferase Gene in a Group of Patients with a Diagnosis of Behavioural Addiction, including Personality Traits.

Gambling Disorder (GD) is characterised by a harmful, enduring, and recurrent involvement in betting-related behaviours. Therefore, GD shares similar biological mechanisms and symptoms to substance use disorders (SUD). Therefore, in this study, we chose the behavioural addictions group. During the examination and recruitment to the study, it turned out that all the people undergoing treatment for gambling addiction were also addicted to amphetamines, which is consistent with the biological mechanism related to cerebral neurotransmission. The aim of the study was to investigate the association of the COMT gene polymorphism with behavioral addiction. The study group consisted of 307 participants: 107 men with gambling disorder and amphetamine dependency (mean age = 27.51, SD = 5.25) and 200 non-addicted, nor dependent, free from neuro-psychiatric disorders control group men (mean age = 20.20, SD = 4.51). Both groups were subjected to psychometric evaluation using the State-Trait Anxiety Inventory and the NEO Five-Factor Personality Inventory. Genomic DNA was extracted from venous blood following standard protocols. Determination of the rs4680 polymorphism in the COMT gene was performed using the real-time PCR technique. Statistically significant differences in the frequency of rs4680 genotypes were found in the tested sample of subjects compared with the control group (p = 0.03543). Subjects with gambling disorder and amphetamine use disorder compared to the control group obtained higher scores in the assessment of the STAI trait scale (p = 0.0019), state scale (p < 0.0000), and NEO-FFI Neuroticism scale (p < 0.0000). Significantly lower results were obtained for the NEO-FFI Agreeability scale (p < 0.0000). Additionally, a significant statistical impact of gambling disorder and amphetamine use disorder, and the COMT rs4680 genotype was demonstrated for the score of the STAI trait (p = 0.0351) and state (p = 0.0343) and the NEO-FFI Conscientiousness scale (p = 0.0018). We conclude that COMT and its polymorphic variant influence the development of addiction. Still, considering its multifactorial and polygenic nature, it should be combined with other factors such as personality.

Association of polymorphisms rs4680 of the Catechol-O-Methyltransferase gene and rs6265 of the brain derived neurotrophic factor gene with the behavioral inhibition and behavioral activation systems.

Background: The Behavioral Inhibition System (BIS) comprises limbic circuitry implicated in avoidance behaviors. Its increased activation has been identified as a risk factor for anxiety and depressive disorders. In addition, both Catechol-O-Methyltransferase (COMT) and Brain Derived Neurotrophic Factor (BDNF) have been postulated as candidate genes that constitute a vulnerability for the onset of anxiety and depressive disorders. The aim of this study was to evaluate the possible association between the rs4680 polymorphism of the COMT gene and the rs6265 polymorphism of the BDNF gene with the BIS and the Behavioral Activation System (BAS) in a population sample from Colombia. Methods: Genetic information was obtained by extracting DNA from blood samples of 80 participants and using Taqman probes designed for each polymorphism. In addition, participants completed a BIS/BAS scale in order to establish a neuropsychological classification. Results: The frequency of the Met allele of the BDNF gene was greater in the group with BIS sensitivity compared to the group with BAS sensitivity. On the contrary, the frequency of the Met allele of the COMT gen did not show a significant association with the BIS. Conclusions: The rs6265 polymorphism of BDNF gene is associated with the BIS which in turn constitutes a risk factor for anxiety and depression.

Are catechol-O-methyltransferase gene polymorphisms genetic markers for pain sensitivity after all? - A review and meta-analysis.

The catechol-O-methyltransferase (COMT) gene has arguably been the designated pain sensitivity gene for nearly two decades. However, the literature provides inconsistent evidence. We performed several meta-analyses including k = 31 samples and n = 4631 participants thereby revealing small effects of rs4680 on pain thresholds in fibromyalgia, headache and across chronic pain conditions. Moreover, rs4680 effects were found across pain patients when affected, but not unaffected, body sites were assessed. No effect was detected for any other SNP investigated. Importantly, our results corroborate earlier findings in that we found a small effect of COMT haplotypes on pain sensitivity. Our review and meta-analysis contribute to the understanding of COMT-dependent effects on pain perception, provide insights into research issues and offer future directions. The results support the theory that rs4680 might only impact behavioural measures of pain when descending pain modulatory pathways are sufficiently challenged. After all, COMT polymorphisms are genetic markers of pain sensitivity, albeit with some limitations which are discussed with respect to their implications for research and clinical significance.

Early life adversity and cardiovascular responses to repeated stress among adolescents: Moderating role of COMT gene rs4680 polymorphism.

BACKGROUND: Early life adversity (ELA) increases the risk of cardiovascular diseases through dysregulation of cardiovascular stress responses manifested by either exaggerated or blunted reactivity. The catechol-O-methyltransferase (COMT) gene rs4680 polymorphism has been identified in gene-environment interaction (G×E) studies to explain individual differences in the effects of ELA on physiological stress responses. However, little is known about whether ELA interacts with COMT gene rs4680 polymorphism to affect cardiovascular responses to repeated stress exposures. OBJECTIVE: The current study examined the associations between ELA and cardiovascular responses to repeated stress exposures, and the moderating role of COMT rs4680 polymorphism in these associations. METHODS: The childhood trauma questionnaire (CTQ) was administered to 359 junior school students who underwent a two-successive stress exposures protocol with continuous cardiovascular monitoring [heart rate (HR) and systolic and diastolic blood pressure (SBP, DBP)] across four laboratory phases, and their saliva samples for deoxyribonucleic acid (DNA) genotyping were collected. RESULTS: ELA was associated with blunted HR reactivity to the first and second stress exposures, blunted SBP reactivity to the first stress exposure, and attenuated SBP habituation to repeated stress exposures. Moreover, COMT rs4680 moderated these associations, such that the associations between ELA and blunted HR, SBP, and DBP reactivity to the first stress and disrupted DBP habituation to repeated stress exposures only existed in GA/AA genotype carriers but not in GG genotype carriers. CONCLUSIONS: These findings suggest that the A allele of COMT rs4680 is vulnerable to the negative effects of ELA on the developmental dysregulation of stress physiological systems.

Gender divergent effect of COMT gene rs4680 polymorphism on the association between executive dysfunction and psychotic-like experiences.

AIM: Premorbid cognitive impairments are observed prior to the onset of schizophrenia. Catechol-O-methyltransferase (COMT) rs4680 is associated with psychosis and plays a crucial role in the development of the executive function. In addition, genetic COMT variations and gender affect its enzymatic activity. Therefore, the aim of this study was to evaluate the impact of COMT rs4680 on the relationship between executive dysfunction and psychotic-like experiences (PLEs) in college students, with the additional investigation of the gender difference. METHODS: A total of 463 students provided biological samples for DNA analysis and the COMT gene rs4680 polymorphism was discriminated by the improved multiplex ligase detection reaction method. They also completed the Prodromal Questionnaire and the Dysexecutive Questionnaire. RESULTS: Executive dysfunction significantly predicted positive PLEs in the total, male and female population (ß = 0.515, 0.508 and 0.512, p < 0.001). The results of moderated analysis revealed that COMT rs4680 recessive genetic model ('AA genotype' versus 'G carrier') moderated the relationship between executive dysfunction and psychotic-like experience in the total and females (p = 0.002 and p <0.001, respectively), but not in males. CONCLUSION: These findings revealed a female-specific effect of COMT rs4680 on the relationship between executive dysfunction and PLEs in young adults.

Association of Catechol-O-Methyltransferase Gene rs4680 Polymorphism and Levodopa Induced Dyskinesia in Parkinson's Disease: A Meta-Analysis and Systematic Review.

INTRODUCTION: Long-term levodopa therapy for Parkinson's disease (PD) can cause levodopa induced dyskinesia (LID). Genetic predisposition has a significant role to play in inter-individual heterogeneity in the clinical manifestation of LID. Despite accumulating evidence for the role of COMT gene polymorphism (rs4680) as a genetic basis for LID, to date results have been inconsistent. Early assessment of the Catechol-O-Methyltransferase (COMT) genotype might be helpful to stratify PD patients concerning their individual risk for LID. METHOD: In this meta-analysis, we have used 9 studies, which were selected through online databases. Statistical analysis was performed using R (v-3.6) software. 5 genetic models have been used in the present study: Allele model (A vs. G), Dominant model (AA+AG vs. GG), Homozygote model (AA vs. GG), Co-dominant/heterozygote model (AG vs. GG), and Recessive model (AA vs. AG + GG). RESULTS: The results indicated a significant association between COMT rs4680 (Val158Met) polymorphism and LID risk. The genotype AA of COMT rs4680 is a risk factor for LID in PD patients under the recessive model (AA vs GG+AG) in the random-effect model. Analysis based on ethnicity showed that COMT rs4680 SNP allele A is a risk factor for LID development in Asian PD patients, while GG genotype is a risk factor for LID development in non-Asian PD patients using different genetic models. CONCLUSION: The results of the present meta-analysis support that the COMT Val158Met polymorphism is a risk factor for the development of LID in PD patients having ethnic variations.

The inconsistent mediating effect of catechol O methyl transferase Val158Met polymorphism on the sex difference of cognitive impairment in schizophrenia patients.

Objective: Schizophrenia is a multifaceted mental disorder characterized by heterogeneous positive/negative symptoms and cognitive deficits. Sex differences have been reported in various aspects of the disease. However, the underlying genetic reasons remain unelucidated. Recent studies show that the influence of COMT Val158Met (rs4680) variation is sexually dimorphic. Thus, this study aims to explore whether there is an effect of the interaction between COMT Val158Met (rs4680) polymorphism and sex on patients' clinical characteristics and cognitive function. Materials and methods: We recruited 367 in patients with chronic schizophrenia (246 males and 121 females) and 419 healthy controls (172 males and 247 females). The cognitive performance was assessed by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and the COMT Val158Met (rs4680) polymorphism is genotyped. The psychopathological symptoms of the patients were assessed by the Positive and Negative Syndrome Scale (PANSS). Results: We find that male patients had a significantly higher proportion of carrying the Val allele and Val/Val carriers exhibited more severe positive symptoms and cognitive impairment than Met carriers. COMT Val158Met (rs4680) polymorphism inconsistently mediated the relationship between sex and cognitive performance in schizophrenia patients. Conclusion: These findings suggest that COMT Val158Met (rs4680) polymorphism is associated with the risk and severity of schizophrenia in a sexually dimorphic way and contributes more to the clinical symptoms and cognitive impairment in male patients with schizophrenia.

Parent-Adolescent Conflict, Depressive Symptoms, and Non-Suicidal Self-Injury among Chinese Adolescents: The Moderating Effect of the COMT Gene rs4680 Polymorphism.

Existing research suggests that parent-adolescent conflict is associated with increased risk for adolescent non-suicidal self-injury (NSSI). However, adolescent NSSI reactions to parent-adolescent conflicts exhibit large individual differences. This study sought to explore whether depressive symptoms mediates the relationship between parent-adolescent conflict and adolescent NSSI, and whether this mediating process is moderated by the COMT gene rs4680 polymorphism. A total of 673 adolescents (364 males, 309 females) in the age range of 12 to 15 years (Meanage = 12.81 years, SD = 0.48) completed questionnaires regarding parent-adolescent conflict, depressive symptoms, and NSSI. Genomic DNA was extracted from saliva and buccal cells from each participant. Bootstrapping techniques displayed statistically significant moderated mediation. The results showed that the positive association between parent-adolescent conflict and adolescent NSSI was in fact mediated by depressive symptoms. Moreover, this indirect link was moderated by the COMT gene rs4680 polymorphism. Specifically, the risk effect of parent-adolescent conflict on adolescent NSSI via depressive symptoms was stronger for adolescents with Val/Val genotype than for those with Met/Met or Val/Met genotype. These findings underscore the importance of examining the interaction between genes and the environment to understand how and when parent-adolescent conflict impacts adolescent NSSI.

Association study of Catechol-O-Methyltransferase (COMT) rs4680 Val158Met gene polymorphism and suicide attempt in Mexican adolescents with major depressive disorder.

AIM: We analyzed the association between SLC6A4, DRD2, COMT and MAOA genes and suicide attempt (SA) in Mexican adolescent patients with major depressive disorder (MDD). METHODS: The sample included 197 adolescents (127 females and 70 males) with principal diagnosis of MDD. Among them, 63 patients had SA at least once and 134 had not SA. The mean age of patients with and without SA was 15 ± 1.4 and 14 ± 1.5 years, respectively. We analyzed the genotype and allele distribution between patients with and without SA of SLC6A4 (5HTTLPR/rs25531), DRD2 (rs6275), COMT (rs4680), and MAOA (uVNTR). RESULTS: We did not find genotype or allele association between SA and SLC6A4 (χ2=0.67, p = 0.71; χ2=0.07, p = 0.77, respectively), DRD2 (χ2=0.05, p = 0.97; χ2=0.003, p = 0.95), and MAOA (females: χ2=0.86, p = 0.64; χ2=0, p = 1/males: χ2=0.008, p = 0.92) genes. However, there were differences in genotype frequencies of COMT/rs4680 between patients with SA and without SA (χ2=11.17, p = 0.003). Also, we observed a high frequency of Met158 allele showing an increased risk of having presented at least one SA (χ2=10.6, p = 0.001; OR = 1.43; 95% CI, 1.17-1.74). CONCLUSIONS: Our findings showed an association between low activity genotype and allele of Val158Met polymorphism of COMT gene and SA in Mexican adolescents with MDD.

An Exploratory Analysis of the Association Between Catechol-O-Methyltransferase and Response to a Randomized Open-Label Placebo Treatment for Cancer-Related Fatigue.

Previous studies have identified catechol-O-methyltransferase (COMT), as a key enzyme influencing sympathetic function. Although the COMT SNP rs4680 and rs4818, are well-studied, little is known about their influence on cancer-related fatigue (CrF) and placebo response. In this study, we examined whether genetic variation in COMT, at the functional SNP rs4680 and linked rs4818, influenced open-label placebo (OLP) responses found in cancer survivors reporting moderate to severe CrF. We randomized cancer survivors (N = 74) reporting moderate-to-severe CrF to receive OLP or to treatment-as-usual (TAU) and assessed if rs4680 and rs4818 were associated with changes in fatigue severity and fatigue-distressed quality of life. At the end of the initial 21 days, the treatments were crossed over and both groups were re-assessed. Participants with the rs4680 high-activity G-allele (G/G or G/A) or rs4818 C/G genotypes reported significant decreases in fatigue severity and improvements in fatigue-distressed quality of life. The COMT rs4818 findings replicated findings in a similar study of OLP in cancer fatigue. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02522988.

Risks of Macrosomia Associated with Catechol-O-Methyltransferase Genotypes and Genetic-Epigenetic Interactions among Children with and without Gestational Diabetes Exposure.

Background: Gestational diabetes mellitus (GDM) is a major macrosomia risk factor. Variations in the catechol-O-methyltransferase (COMT; rs4680) genotypes are associated with heightened susceptibility to environmental exposures and nutritional conditions. However, macrosomia risks associated with COMT genetics, epigenetics, and the interaction between genetic and epigenetics among children with and without exposure to GDM are unknown. Methods: Data from women/children pairs (n = 1087) who participated in the Tianjin Gestational Diabetes Birth Cohort were used to examine the odds of being born with macrosomia associated with COMT-genotypes, 55 CpG sites located on the COMT gene, and genetic and epigenetic interactions. Odds of macrosomia associated with COMT genetic, epigenetic, genetic and epigenetic interactions, and moderations with GDM were tested using adjusted logistic regression models. Results: Overall, 16.1% (n = 175) of children were born with macrosomia. Models showed that children with at least one copy of the minor allele (A) had higher odds of macrosomia (odds ratio, 1.82; 95% confidence interval 1.25-2.64) compared with children with the GG-genotype. After false discovery rate corrections, none of the 55 CpG sites located on the COMT gene was associated with odds of macrosomia. The genetic and epigenetic associations were not modified by exposure to GDM. Conclusion: Findings suggest carriers of the COMT GG-genotype had lower odds of macrosomia, and this association was not modified by epigenetics or exposure to GDM.

The COMT rs4680 polymorphism, family functioning and preschoolers' attentional control indexed by intraindividual reaction time variability.

Trial-to-trial intraindividual reaction time variability (IIRTV) serves as an index of attentional control and related endogenous brain function. What determinants contribute to preschoolers' attentional control indexed by IIRTV remains unknown. The present study examined how catechol-o-methyltransferase (COMT) rs4680 polymorphism interacted with family functioning (cohesion and adaptability) to impact on preschoolers' attentional control indexed by IIRTV. One hundred forty-four preschool children (Mage  = 4.19, SD = 0.63) completed the flanker task to assess their IIRTV. Their parents were asked to fill out the Family Adaptability and Cohesion Evaluation Scale II to assess family functioning. After controlling for age, socioeconomic status (SES) and mean reaction time, results showed that the COMT rs4680 polymorphism was positively associated with preschoolers' IIRTV at the 5% significance level (p = .02) but not after multiple testing adjustment (p = .08). Moreover the COMT rs4680 polymorphism significantly interacted with family functioning to impact on preschoolers' IIRTV and the interaction effects remained significant after correction for multiple testing (p = .01, ΔR2  = 0.06 in congruent conditions; p = .04, ΔR2  = 0.04 in combined conditions). In addition, the significant interaction between SES and COMT rs4680 polymorphism was also found in the present study (p = .01, ΔR2  = 0.05 in congruent conditions; p = .05, ΔR2  = 0.03 in combined conditions). No sex differences were found in the present sample. The findings of the present study expand our knowledge about the gene × environment underpinnings of children's attentional control and endogenous brain function, and provide evidence for the Vantage Sensitivity model on children's development.

The association between sleep-wake ratio and overnight picture recognition is moderated by BDNF genotype.

A wealth of studies supports the role of sleep in memory performance. Experimentally controlled studies indicate that prolonged wake after memory encoding is detrimental for memory outcome whereas sleep protects from wake-time interference and promotes memory consolidation. We examined how the natural distribution of wake and sleep between encoding and retrieval associated with overnight picture recognition accuracy among 161 adolescents following their typical sleep schedule with an in-home polysomnography. The memorized pictures varied in their level of arousal (calm to exciting) and valence (negative to positive). Suspecting genotypic influence on the sensitivity for sleep/wake dynamics, we also assessed if these associations were affected by known gene polymorphisms involved in neural plasticity and sleep homeostasis: brain-derived neurotrophic factor (BDNF) Val66Met and Catechol-O-methyltransferase (COMT) Val158Met. In the whole sample, overnight recognition accuracy was associated with the levels of arousal and valence of the pictures, but not with sleep percentage (i.e. the percentage of time spent asleep between memory encoding and retrieval). While the allelic status of BDNF or COMT did not have any main effect on recognition accuracy, a significant moderation by BDNF Val66Met was found (p = .004): the subgroup homozygous for valine allele showed positive association between sleep percentage and recognition accuracy. This was underlain by detrimental influence of wake, rather than by any memory benefit of sleep. Our results complement the mounting evidence that the relation between sleep and memory performance is moderated by BDNF Val66Met. Further studies are needed to clarify the specific mechanisms.

First Demonstration of Double Dissociation between COMT-Met158 and COMT-Val158 Cognitive Performance When Stressed and When Calmer.

We present here the first evidence of the much-predicted double dissociation between the effect of stress on cognitive skills [executive functions (EFs)] dependent on prefrontal cortex (PFC) by catechol-O-methyltransferase (COMT) genotype. The COMT gene polymorphism with methionine (Met) at codon 158 results in more dopamine (DA) in PFC and generally better EFs, while with valine (Val) at codon 158 the result is less PFC DA and generally poorer EFs. Many have predicted that mild stress, by raising PFC DA levels should aid EFs of COMT-Vals (bringing their PFC DA levels up, closer to optimal) and impair EFs of COMT-Mets (raising their PFC DA levels past optimal). We tested 140 men and women in a within-subject crossover design using extremely mild social evaluative stress. On trials requiring EFs (incongruent trials) of the Flanker/Reverse Flanker task, COMT-Val158 homozygotes performed better when mildly stressed than when calmer, while COMT-Met158 carriers performed worse when mildly stressed. Two other teams previously tried to obtain this, but only found stress impairing EFs of COMT-Mets, not improving EFs of COMT-Vals. Perhaps we found both because we used a much milder stressor. Evidently, the bandwidth for stress having a facilitative effect on EFs is exceedingly narrow.

Association between COMT gene Val108/158Met and antidepressive treatment response: A meta-analysis.

Multiple antidepressive treatment methods are widely used in the clinic, but different patients showed considerable differences in response to the same treatment. The catechol-O-methyltransferase (COMT) rs4680 polymorphism is involved in the antidepressive treatment reaction; however, the results in different studies are inconsistent. Thus, we performed a meta-analysis to explore the association of the COMT rs4680 polymorphism with the treatment response in major depressive disorder (MDD) patients. An online search was performed through PubMed, EMBASE and the Cochrane library up to December 2018. The odds ratios (ORs), 95% confidence intervals (95% CI) and heterogeneity were calculated in four genetic models. Subgroup analysis and Galbraith plot were carried out to detect the potential source of heterogeneity. Sensitivity and publication bias analyses were performed to identify the reliability of the results. A total of 11 studies involving 2845 individuals were included in this meta-analysis. The results of the subgroup analysis indicated that patients who carried the G allele had remission or a better response to electroconvulsive therapy (ECT) in four genetic models. Excluding the studies that might lead to heterogeneity, overall ORs were recalculated, and no obvious association between rs4680 polymorphism and therapeutic reaction was detected in the allelic, recessive and additive models. In the dominant model, COMT rs4680 variants showed significant associations with antidepressive treatment, but the result was highly dependent on the individual study. In addition, the patients with the GG or AG + GG genotype in comparison to AA were associated with a better response to ECT treatment. However, due to the small number of studies using ECT treatment, we suggest that more research should be performed to verify this result.

Relations between catechol-O-methyltransferase Val158Met genotype and inhibitory control development in childhood.

The Val158Met rs4680 single-nucleotide polymorphism (SNP) at the catechol-O-methyltransferase (COMT) gene, primarily involved in dopamine breakdown within prefrontal cortex, has shown relations with inhibitory control (IC) in both adults and children. However, little is known about how COMT genotype relates to developmental trajectories of IC throughout childhood. Here, our study explored the effects of the COMT genotype (Val/Val, Val/Met, and Met/Met) on IC trajectories between the ages of 5 and 10 years. Children (n = 222) completed a Go/Nogo task at ages 5, 7, and 10; IC was characterized using signal detection theory to examine IC performance (d') and response strategy (RS) (criterion). COMT genotype was not related to initial levels of IC performance and RS at age 5 or change in RS from ages 5 to 10. In contrast, COMT genotype was related to change in IC performance between 5 and 10 years. While Val/Val children did not differ from Val/Met children in development of IC performance, children with the Met/Met genotype exhibited more rapid development of IC performance when compared with Val/Met peers. These results suggest that COMT genotype modulates the development of IC performance in middle childhood.

Catechol-O-Methyltransferase Gene Val158Met Polymorphism Moderates the Effect of Social Exclusion and Inclusion on Aggression in Men: Findings From a Mixed Experimental Design.

Accumulating research has identified the interactive effects of catechol-O-methyltransferase (COMT) gene Val158Met polymorphism and environmental factors on aggression. However, available evidence was mainly based upon correlational design, which yields mixed findings concerning who (Val vs. Met carriers) are more affected by environmental conditions and has been challenged for the low power of analyses on gene-environment interaction. Drawing on a mixed design, we scrutinized how COMT Val158Met polymorphism (between-group variable) impacts on aggression, assessed by hostility, aggressive motivation, and aggressive behavior, under different social conditions (exclusion vs. inclusion, within-group variable) in a sample of 70 Chinese male undergraduate students. We found that both Val/Val homozygote and Met alleles carriers showed differences in the feelings of hostility and aggressive motivation under conditions of exclusion versus inclusion, but these differences were more pronounced for Met allele carriers. These findings implied that COMT Val158Met polymorphism did not respond to environmental stimuli in an all-or-none way and shed light on the importance of examining the gene-environment interaction using a mixed design.

Effect of catechol-O-methyltransferase (rs4680) single-nucleotide polymorphism on opioid-induced hyperalgesia in adults with chronic pain.

The catechol-O-methyltransferase Val158Met polymorphism has been associated with alterations in pain perception, but the influence of the polymorphism on pain perception in patients with chronic pain receiving daily opioid therapy has not been previously reported. The primary aim of this study was to investigate the effects of the catechol-O-methyltransferase Val158Met polymorphism on heat pain perception in a cohort of adults receiving daily opioid therapy for chronic pain. Adults with chronic pain consecutively admitted to an outpatient pain rehabilitation program who met inclusion criteria and were receiving daily opioid therapy were recruited for study participation (N = 142). Individuals were genotyped for catechol-O-methyltransferase Val158Met (rs4680), and the polymorphism was analyzed using an additive and codominant genotype models. The distribution of the Val158Met genotypes was 25% for Val/Val, 41% for Val/Met and 34% for Met/Met (Hardy-Weinberg, P > 0.05). A main effect of genotype was observed for heat pain perception ( P = 0.028). Under the codominant model of allele effects, exploratory post hoc pairwise comparisons adjusted for morphine equivalent dose and pain catastrophizing demonstrated that individuals with the Val/Met genotype were hyperalgesic compared to individuals with the Val/Val ( P = 0.039) and Met/Met ( P = 0.023) genotypes. No significant association was observed between heat pain perception and genotype under the additive model of allele effects. Among patients with chronic pain who were receiving daily opioids, the Val/Met genotype was associated with hyperalgesia using a measure of heat pain perception that has been previously indicative of opioid-induced hyperalgesia in other heterogeneous samples of adults with chronic pain. This study contributes to the emerging understanding of how catechol-O-methyltransferase activity affects pain perception in the context of daily opioid use, and these findings may be useful in the design of future trials aimed at investigating the potential efficacy of ß-2 adrenergic receptor antagonism for opioid-induced hyperalgesia.