In addition, homozygous COMT-deficient female (but not male) mice displayed impairment in emotional reactivity in the dark/light exploratory model of anxiety.
The presentations were (1) Two functional polymorphisms and their intermediate phenotypes in complex behaviors: COMT/executive cognition and anxiety and HTT/anxiety, by David Goldman; (2) Role of the EEG in determining genetic risk for alcoholism and anxiety disorders, by Mary-Anne Enoch; (3) The response to alcohol as an intermediate phenotype for alcoholism, by Marc A. Schuckit; and (4) Pharmacogenomic approaches to alcoholism treatment: toward a hypothesis, by Bankole A. Johnson.
Functional alleles that alter alcoholism-related intermediate phenotypes include common alcohol dehydrogenase 1B and aldehyde dehydrogenase 2 variants that cause the aversive flushing reaction; catechol-O-methyltransferase (COMT) Val158Met leading to differences in three aspects of neurobiology: executive cognitive function, stress/anxiety response, and opioid function; opioid receptor micro1 (OPRM1) Asn40Asp, which may serve as a gatekeeper molecule in the action of naltrexone, a drug used in alcoholism treatment; and HTTLPR, which alters serotonin transporter function and appears to affect stress response and anxiety/dysphoria, which are factors relevant to initial vulnerability, the process of addiction, and relapse.
Association between the COMTVal158Met polymorphism and propensity to anxiety in an Australian population-based longitudinal study of adolescent health.
These data suggest that involvement of the COMT locus in susceptibility to anxiety-related traits (ie low extraversion and high neuroticism) is unlikely to be wholly accounted for by the well-studied rs4680 ('val/met') polymorphism.
The COMT Met158 allele leads to lower COMT activity and has also been associated with anxiety, and the effect of this gene is apparently additive with HTTLPR.
The paper focuses on such candidate gene polymorphisms that alter alcoholism-related intermediate phenotypes including: dopaminergic system polymorphic variants (DRD2 -141C Ins/Del in promoter region, exon 8 and DRD2 TaqI A and DAT 40bp VNTR genes polymorphisms) that cause predisposition to severe alcoholism (haplotype Ins/G/A2); COMTVal158Met gene polymorphism related to differences in executive cognitive function and 5-HTT gene promoter polymorphism, which alters stress response and affects anxiety and dysphoria.
Catechol O-methyltransferase (COMT), the major enzyme determining cortical dopamine flux, has a common functional polymorphism (val(158)met) that affects prefrontal function and working memory capacity and has also been associated with anxiety and emotional dysregulation.
In the 22q11.2 deletion syndrome group, baseline subthreshold psychotic symptoms interacted both with the COMT genotype and with baseline symptoms of anxiety or depression to predict 61% of the variance in severity of psychosis at follow-up evaluation.
COMTVal(158)Met and 5HTTLPR functional loci interact to predict persistence of anxiety across adolescence: results from the Victorian Adolescent Health Cohort Study.
Many of these differences are unconfirmed or minor, but some appear to be of reasonable robustness and magnitude; eg the functional Val(158)Met polymorphism in COMT is associated with obsessive-compulsive disorder in men, with anxiety phenotypes in women, and has a greater impact on cognitive function in boys than girls.
The COMT gene contains a functional polymorphism changing enzyme activity that has been associated with some neuropsychiatric (endo)phenotypes, e.g. cognitive performance and anxiety.
Two common functional polymorphisms in catechol-O-methyltransferase (COMTVal158Met) and brain-derived neurotrophic factor (BDNF Val66Met) genes have been implicated in the neurobiology of anxiety and depression.
In this study we investigate the association between three SNPs from COMT and anxiety and depression disorders and neuroticism all measured within the same study sample.
The COMT genotype distribution was similar between controls and individuals in the groups with anxiety and depression using cut-off scores of > or = 8.
A coding variant in one such gene, encoding the dopamine catabolic enzyme catechol-O-methyltransferase (COMTVal158Met), has previously been associated with anxiety and with anxiety-related temperament and altered neural responses to affective stimuli in healthy individuals.
The COMT (catechol-O-methyltransferase) gene has been linked to a spectrum of human phenotypes, including cognition, anxiety, pain sensitivity and psychosis.
The catechol-O-methyltransferase (COMT) Val158Met polymorphism has been found to affect fear extinction and might play a role in the etiology of anxiety disorders.
Furthermore patients carrying a COMT val-allele tend to report more anxiety and more depression symptoms as compared to those with the met/met genotype.
Since pain syndromes as well as anxiety and depression are associated to low and high COMT activity respectively and these conditions are all associated with irritable bowel syndrome (IBS) we wanted for the first time to explore the relationship between the polymorphism and IBS.
The present results provide further support for a-potentially female-specific-role of the COMTval158met polymorphism in the genetic and neural underpinnings of anxiety- and depression-related intermediate phenotypes and may aid in further clarifying the differential role of COMT genotype driven dopaminergic tonus in the processing of emotionally salient stimuli.