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Introduction: The role of catechol-O-methyltransferase (COMT) in catecholamine neurotransmitter metabolism has led to the investigation of variants of the corresponding gene in the etiology of different psychiatric disorders, but the results are inconclusive. Methods: We have examined the relationship between COMT Val158Met single nucleotide polymorphism (rs4680) and the occurrence of psychiatric disorders in a highly representative birth cohort sample of young adults in the Estonian Children Personality Behaviour and Health Study (original n = 1,238). The lifetime occurrence of psychiatric disorders at the age of 25 years was assessed with the Mini-International Neuropsychiatric Interview. Results: Both Val- and Met-alleles of the COMT Val158Met were associated with specific psychiatric disorders. Met-allele carriers had a significantly higher occurrence of agoraphobia (3.2% vs. 0.5%; χ2 = 4.10; p < 0.05) compared to Val/Val homozygotes. Also, the occurrence of panic disorder was significantly higher in female Met-allele carriers than in Val/Val homozygote females (10.2% vs. 3.6%; χ2 = 4.62 p = 0.03). In contrast, the occurrence of generalized anxiety disorder was higher in Val/Val females when compared to Met-allele carriers (12.7% vs. 6.8%; χ2 = 4.16; p = 0.04). Also, female Val/Val homozygotes (15.5%) had a higher occurrence of eating disorders than Met-allele carriers (6.1%) of the COMT Val158Met polymorphism (χ2 = 10.39; p = 0.002). In the whole sample, Met-allele homozygotes had a higher occurrence of alcohol use and substance use disorders than Val-allele carriers (χ2 = 3.62 and 3.68, respectively; p < 0.05). Conclusion: In a regional highly birth cohort representative sample, either COMT rs4680 variant was observed in association with specific psychiatric disorders. [ABSTRACT FROM AUTHOR]

Background: Genetic factors were suggested to have influence on the development of post-traumatic stress disorder (PTSD). The possible association between catechol-O-methyltransferase (COMT) Val158Met polymorphism and PTSD has been evaluated in several studies. But the results were still controversial. Therefore, we conduct this meta-analysis to address these issues. Methods: The PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched for eligible studies. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to estimate the association between COMT Val158Met polymorphism and PTSD. Results: Five articles including 6 studies with 893 cases and 968 controls were finally included in the present meta-analysis. The pooled analyses did not demonstrate a significant association between the COMT Val158Met polymorphism and PTSD in any of the selected genetic models: allele model (OR = 1.13, 95% CI: 0.97–1.31), dominant model (OR = 1.17, 95% CI: 0.93–1.46), recessive model (OR = 1.44, 95% CI: 0.78–2.66), and additive model (OR = 1.54, 95% CI: 0.85–2.80). Subgroup analyses suggested that the Hardy-Weinberg equilibrium status of genotype distributions could influence the relationship of COMT Val158Met polymorphism and PTSD. Conclusions: The present meta-analysis suggested that the COMT Val158Met polymorphism may not be associated with the PTSD risk. Further large-scale and population-representative studies are warranted to evaluate the impact of the COMT Val158Met polymorphism on the risk of PTSD. [ABSTRACT FROM AUTHOR]

Mismatch negativity (MMN) is a component of auditory event-related potentials that reflects automatic change detection in the brain, showing qualities of endophenotypes in schizophrenia. MMN deficiency is one of the robust findings in patients, and it reflects both cognitive and functional decline. Catechol-o-methyltransferase (COMT) is a key enzyme involved in regulating dopamine transmission within the prefrontal cortex. A preliminary study suggested that the COMTVal108/158Met genotype (rs4680) is related to cognitive function in schizophrenia. Both the COMTVal108/158Met genotype and MMN are related to cognitive function, but no studies have reported on the relationship between MMN and the COMTVal108/158Met genotype in schizophrenia. This study therefore examined the relationship between COMTVal108/158Met genotype and MMN. The duration of MMN was measured, and the COMTVal108/158Met polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism in 49 Japanese schizophrenia patients (Val/Val, n = 21; Met carriers, n = 28). Amplitude and latency of MMN were compared between Val/Val and Met carriers. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder (BD) has been associated with temperamental and personality traits, although the relationship is still to be fully elucidated. Several studies investigated the genetic basis of temperament and character, identifying catechol-O-methyltransferase (COMT), brain derived neurotrophic factor (BDNF), and serotonin transporter (5-HTT) gene variants as strong candidates. Methods: In the GECO-BIP study, 125 BD patients and 173 HC were recruited. Subjects underwent to a detailed assessment and the temperament and character inventory 125 items (TCI) was administrated. Three functional genetic variants within key candidate genes (COMT rs4680, BDNF rs6265, and the serotonin-transporter-linked polymorphic region (5-HTTLPR)) were genotyped. Univariate and multivariate analyses were performed. Results: Compared to HC, BD patients showed higher scores in novelty seeking (NS; p = 0.001), harm avoidance (HA; p < 0.001), and self transcendence (St; p < 0.001), and lower scores in self directness (p < 0.001) and cooperativeness (p < 0.001) TCI dimensions. Concerning the genetic analyses, COMT rs4680 was associated with NS in the total sample (p = 0.007) and in the male subsample (p = 0.022). When performing the analysis in the HC and BD samples, the association was confirmed only in HC (p = 0.012), and in the HC male subgroup in particular (p = 0.004). BDNF rs6265 was associated with St in the BD group (p = 0.017). Conclusion: COMT rs4680 may modulate NS in males in the general population. This effect was not detected in BD patients, probably because BD alters the neurobiological basis of some TCI dimensions. BDNF rs6265 seems to modulate St TCI dimension only in BD patients, possibly modulating the previously reported association between rs6265 and BD treatment response. Further studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Background: Because major depression and panic disorder are both more prevalent among females and since several lines of evidence suggest that genetic factors might influence an individual's vulnerability to panic disorder, gene-gender interactions are being examined in such psychiatric disorders and mental traits. A number of studies have suggested that specific genes, e.g. catechol-O-methyltransferase (COMT), might lead to distinct clinical characteristics of panic disorder. Method: We compared gender-specific personality-related psychological factors of 470 individuals with panic disorder and 458 healthy controls in terms of their COMT Val158Met polymorphism and their scores on the Revised NEO Personality Inventory (NEO PI-R) and State-Trait Anxiety Inventory (STAI) with a 1-way analysis of covariance. Results: In the male panic disorder patients, the NEO PI-R score for openness to experience was significantly lower in the Met/Met carrier group, whereas there was no such association among the female panic disorder patients or the male or female control groups. Conclusion: The gender-specific effect of the COMT genotype suggests that the COMT Val/Met genotype may influence a personality trait, openness to experience, in males with panic disorder. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and Aims: Literature findings mainly support the notion that suicide attempts (SA) and self-mutilating behavior (SMB) are distinct behaviors, although they may share common psychopathological features. In the present paper we aimed to identify behavioral phenotypes in patients with SA, SMB, or both (SAM) and to analyze the association with candidate genes. Methods: One hundred forty-two inpatients with a history of SA (n = 86), SMB (n = 22), and SAM (n = 39) were included in this study. Subjects were evaluated using the Tridimensional Personality Questionnaire (TPQ) and the Buss-Durkee Hostility Inventory (BDHI). Polymorphisms within serotonin transporter (SLC6A4, HTTLPR), catechol-O-methyl transferase (COMT, Val158Met), and tryptophan hydroxylase (TPH, 218C>A) were also analyzed. Results: Principal component factor analysis including the BDHI and TPQ produced 3 factors that could classify the 3 groups of patients with good sensitivity. However, only the 'pure suicidal' factor had a sufficient positive predictive value. This factor was characterized by high levels of persistence (PS) and, to a lower extent, reward dependence. The distribution of genotypes was not different across patient groups for all polymorphisms, but the SS genotype of HTTLPR was significantly associated with the 'self-mutilation' factor, characterized by high levels of hostile traits, novelty seeking, and harm avoidance. Conclusion: The results of the present study suggest that different and overlapping temperamental traits in suicidal and self-mutilating patients are present, although only high levels of PS could predict SA repetition. Finally, HTTLPR may mediate the risk for SMB through modulation of some temperamental traits. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The transcription factor AP-2β has been shown to impact clinical and neuropsychological properties. Apparently, it regulates the transcription of genes that code for molecules which are part of the catecholaminergic transmission system. This investigation focuses on possible effects of the transcription factor AP-2β intron 2 polymorphism on cognitive performance parameters. Methods: This hypothesis-driven investigation examined the effects and interactions of the transcription factor AP-2β intron 2 polymorphism, the Val158Met catechol-O-methyltransferase (COMT) polymorphism, and the variable number of tandem repeat polymorphism of monoamine oxidase A (MAOA) on cognitive performance parameters within a group of 200 healthy women (age: mean ± SD, 23.93 ± 3.33 years). Results: The AP-2β polymorphism significantly influenced cognitive performance (in particular, the Trail Making Test part B), whereas the MAOA and COMT polymorphisms did not. However, there was an interaction effect of the AP-2β × MAOA × COMT genotypes on the decision bias β of the degraded-stimulus version of the continuous performance task. Only the Val158Met COMT polymorphism showed an influence on personality questionnaires (openness and self-transcendence; NEO Five-Factor Inventory, Temperament and Character Inventory). Conclusion: The transcription factor AP-2β intron 2 polymorphism had more influence on cognition than the MAOA and COMT polymorphisms. Possibly, the AP-2β genotype might influence cognition through pathways other than those that regulate MAOA and COMT transcription. Interactions of transcription factor AP-2β, COMT, and MAOA polymorphisms suggest higher leverage effects of transcription factor AP-2β in subjects with high dopamine availability. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Genetic factors and catecholaminergic dysfunction have been suggested as the etiology of suicide. The catechol-O-methyltransferase (COMT) 158Val/Met polymorphism affects COMT activity; that is, the alleles encoding Val and Met are associated with relatively high and relatively low COMT activity, respectively. We aimed to identify the role of the COMT Val158Met polymorphism in suicidal attempt behavior. The COMT 158Val/Met polymorphisms were analyzed in 197 suicide attempters (male/female: 70/127), 170 control subjects (male/female: 85/85). All subjects were ethnic Korean. The Lethality Suicide Attempt Rating Scale (LSARS) and risk-rescue rating (RRR) system were explored. For the male subjects, there was a significant difference in genotype distributions and allele frequencies between control subjects and suicide attempters. That is, Val/Val genotype and Val carriers were more frequent in suicide attempters than in control subjects. For the female subjects, however, no significant difference was shown in genotype distributions and allele frequencies between control subjects and suicide attempters. There were no significant differences in LSARS and RRR according to the genotypes. The distribution of the COMT 158Val/Met polymorphism showed a biologically meaningful difference between control subjects and suicide attempters among the male subjects although selection bias should be considered. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Disgust is a basic emotion that involves feelings of revulsion and withdrawal behavior from dangerous/infectious situations. Very little is known about the genetic basis of disgust sensitivity. The dopamine receptor D4 (DRD4) and catechol-O-methyltransferase (COMT) genes have been implicated in neuroticism-related traits and approach-related temperaments which are supposed to be associated with disgust sensitivity. The present study aimed to investigate the possible relationship between disgust sensitivity and COMT Val158Met and DRD4 variable number of tandem repeats (VNTR) polymorphisms in healthy subjects. Methods: In total, 241 healthy Korean college students were recruited, and the 228 participants with a complete data set (127 males and 101 females) were included in the data analysis. Disgust sensitivity was assessed using the Disgust Scale-Revised (DS-R) and genotyping of COMT Val158Met and DRD4 VNTR polymorphisms was performed. Results:The Val/Val groups of COMT had significantly higher scores than the non-Val/Val group for the Animal-Reminder and the Contamination-Based Disgust scores as well as for total DS-R scores. Additionally, the non-2-repeat allele group of DRD4 had a tendency to a significantly higher disgust sensitivity than the 2-repeat allele group for Contamination-Based Disgust. Conclusions: These findings suggest that disgust sensitivity may be affected by genetic components, such as dopamine-related genes. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to evaluate functional catechol-O-methyltransferase (COMT) genetic variation as a risk factor for eating disorders (ED). Method: Eighty women receiving treatment for serious ED (52 for anorexia nervosa, 28 for bulimia nervosa) and 116 age-matched females in the control group underwent COMT genotyping for polymorphism in exon 4 (codon 158). Both the low-activity allele and the high-activity allele (H) were determined. Results: The H/H genotype was twice as frequent in the ED group as in the control group (52.5% in the ED group and 25% in controls, χ2 = 15.5, d.f. = 2, p < 0.001, odds ratio = 3.343). The H/H genotype was found in 57.7% of anorexia nervosa patients (χ2 = 16.860, p < 0.001, Hardy-Weinberg equilibrium = 0.003, odds ratio = 4.202). The H allele (val) was discovered in 66.9% of ED patients in comparison to 47.8% of patients from the control group (χ2 = 13.89, p < 0.001, odds ratio = 6.088). In the anorexia group, H allele frequency was enhanced even higher (70.2 vs. 47.8%, χ2 = 14.48, p < 0.001, odds ratio = 8.175). The genotype associations in the subgroup of bulimia patients were not significant, but a trend for a higher frequency of the H allele was found (p = 0.084, odds ratio = 5.309). Conclusions: These findings seem to suggest that a turnover of catecholamines, connected with polymorphism determining high activity of COMT enzyme, is connected with the risk of ED occurrence, particularly anorexia nervosa. The risk is significantly higher for women with an allele of higher activity. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Cognitive and motor deficits have been proposed as markers of abnormal neurodevelopment in schizophrenia and have been associated with genetic liability. In a multicenter study involving 106 subjects, 56 with deficit schizophrenia and 50 with nondeficit schizophrenia, we tested the hypothesis that the catechol-O-methyltransferase (COMT) Val158Met polymorphism is associated with cognitive and motor deficits either in schizophrenia as a whole or in its deficit subtype. The COMT Val158Met polymorphism shared 6.6% of the executive/attention dysfunction variance in patients with schizophrenia and 15.6% of the motor impairment variance in patients with deficit schizophrenia. These results support the hypothesis that the COMT Val158Met polymorphism influences executive functions in schizophrenia and the neuromotor performance in the deficit subtype only. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Human personality traits, which are substantially heritable, may be modulated by monoamine neurotransmitters. It has been demonstrated that the catechol-O-methyltransferase (COMT) Val158Met genetic polymorphism, a functional polymorphism that may affect monoamine metabolism, is possibly associated with specific personality traits. In addition, a polymorphism in the dopamine D4 receptor (DRD4) gene exon 3 has been associated in some, but not all, studies with the novelty seeking personality trait, as evaluated by the Tridimensional Personality Questionnaire (TPQ). In this study, associations between these two polymorphisms and TPQ personality traits were investigated in a sample population of 120 healthy young Chinese females. The results of this analysis reveal that the COMT Val158Met polymorphism was significantly associated with novelty seeking (p = 0.017) and reward dependence scores (p = 0.015) in our sample. However, no significant differences were demonstrated comparing TPQ-specific scores for subjects bearing different DRD4 genotypes. The present study suggests that the functional COMT Val158Met genetic polymorphism contributes to individual differences in the personality traits novelty seeking and reward dependence. Similar to the results of a recent meta-analytic review, however, no association was demonstrated between this DRD4 polymorphism and novelty seeking in our young Chinese female sample population. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The gene coding for catechol-O-methyltransferase (COMT), which is involved in the metabolism of catecholamines, has long been implicated as a candidate gene for schizophrenia.This study aimed to assess the relationship between a functional polymorphism (Val158Met) of the COMT gene and age of onset (AOO), symptomatology, global cognitive function and prognosis in patients with schizophrenia. The study enrolled 154 patients with schizophrenia from chronic wards. Results failed to show a significant association between the Vall58Met polymorphism and the Brief Psychiatric Rating Scale scores, Mini-Mental State Examination scores, and Social and Occupational Functioning Assessment Scale scores, but COMT Val158Met heterozygotes had a later AOO than homozygous patients. However, by further expanding the number of patients to 228 patients, the differences in AOO among thethree COMT genotypicgroupswas not significant. The COMTVaI158Met polymorphism did not appearto significantly affect susceptibility, symptomatology, global cognitive function and prognosis in Chinese patients with schizophrenia, but the possible association with AOO merits further investigation. [ABSTRACT FROM AUTHOR]

The catechol-O-methyltransferase (COMT) gene was thought to be a candidate gene for schizophrenia because of its role in inactivating dopamine. This study examined the relationship between a functional polymorphism (val158met) of the COMT gene, schizophrenia and its associated behaviors. One hundred and ninety-eight Chinese schizophrenic patients and 188 controls were genotyped by polymerase chain reaction restriction fragment length polymorphism. Of the schizophrenic patients, 72 had a history of violence and 62 had a history of suicide attempts. The results failed to show significant association between val158met polymorphism and schizophrenia, violence or suicide. However, our results showed a significant difference in age at disease onset among different genotypes (F = 5.501, p = 0.005).Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder (BD) has been associated with temperamental and personality traits, although the relationship is still to be fully elucidated. Several studies investigated the genetic basis of temperament and character, identifying catechol-O-methyltransferase (COMT), brain derived neurotrophic factor (BDNF), and serotonin transporter (5-HTT) gene variants as strong candidates., Methods: In the GECO-BIP study, 125 BD patients and 173 HC were recruited. Subjects underwent to a detailed assessment and the temperament and character inventory 125 items (TCI) was administrated. Three functional genetic variants within key candidate genes (COMT rs4680, BDNF rs6265, and the serotonin-transporter-linked polymorphic region (5-HTTLPR)) were genotyped. Univariate and multivariate analyses were performed., Results: Compared to HC, BD patients showed higher scores in novelty seeking (NS; p = 0.001), harm avoidance (HA; p < 0.001), and self transcendence (St; p < 0.001), and lower scores in self directness (p < 0.001) and cooperativeness (p < 0.001) TCI dimensions. Concerning the genetic analyses, COMT rs4680 was associated with NS in the total sample (p = 0.007) and in the male subsample (p = 0.022). When performing the analysis in the HC and BD samples, the association was confirmed only in HC (p = 0.012), and in the HC male subgroup in particular (p = 0.004). BDNF rs6265 was associated with St in the BD group (p = 0.017)., Conclusion: COMT rs4680 may modulate NS in males in the general population. This effect was not detected in BD patients, probably because BD alters the neurobiological basis of some TCI dimensions. BDNF rs6265 seems to modulate St TCI dimension only in BD patients, possibly modulating the previously reported association between rs6265 and BD treatment response. Further studies are needed to confirm our findings., (© 2018 S. Karger AG, Basel.)