Catechol-O-methyltransferase (COMT): a gene contributing to sex differences in brain function, and to sexual dimorphism in the predisposition to psychiatric disorders.
paper
Cited
Public
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- Authors
- Harrison, Paul J; Tunbridge, Elizabeth M
- Year
- 2008
- Journal
- Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
- PMID
- 17805313
- DOI
- 10.1038/sj.npp.1301543
Sex differences in the genetic epidemiology and clinical features of psychiatric disorders are well recognized, but the individual genes contributing to these effects have rarely been identified. Catechol-O-methyltransferase (COMT), which metabolizes catechol compounds, notably dopamine, is a leading candidate. COMT enzyme activity, and the neurochemistry and behavior of COMT null mice, are both markedly sexually dimorphic. Genetic associations between COMT and various psychiatric phenotypes frequently show differences between men and women. 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. Sex-specific effects of COMT are usually attributed to transcriptional regulation by estrogens; however, additional mechanisms are likely to be at least as important. Here we review the evidence for a sexually dimorphic influence of COMT upon psychiatric phenotypes, and discuss its potential basis. We conclude that despite the evidence being incomplete, and lacking a unifying explanation, there are accumulating and in places compelling data showing that COMT differentially impacts on brain function and dysfunction in men and women. Since sex differences in the genetic architecture of quantitative traits are the rule not the exception, we anticipate that additional evidence will emerge for sexual dimorphisms, not only in COMT but also in many other autosomal genes.
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| Dopamine metabolism in adults with 22q11 deletion syndrome, with and without schizophrenia--relationship with COMT ValΒΉβ°βΈ/ΒΉβ΅βΈMet polymorphism, gender and symptomatology. | Boot E et al. | β | 2011 | β |
| Gender-specific expression of the DRD4 gene on adolescent delinquency, anger and thrill seeking. | Dmitrieva J et al. | β | 2011 | β |
| Importance of the COMT gene for sex differences in brain function and predisposition to psychiatric disorders. | Tunbridge EM et al. | β | 2011 | β |
| Influence of the COMT genotype on working memory and brain activity changes during development. | Dumontheil I et al. | β | 2011 | β |
| Interactive effects of DAOA (G72) and catechol-O-methyltransferase on neurophysiology in prefrontal cortex. | Nixon DC et al. | β | 2011 | β |
| Introduction to the interaction between gonadal steroids and the central nervous system. | Marshall KM | β | 2011 | β |
| No association between the Catechol-O-Methyltransferase (COMT) val158met polymorphism and cognitive improvement following cognitive remediation therapy (CRT) in schizophrenia. | Greenwood K et al. | β | 2011 | β |
| Personalized medicine can pave the way for the safe use of CBβ receptor antagonists. | Lazary J et al. | β | 2011 | β |
| Sensory gating deficit is associated with catechol-O-methyltransferase polymorphisms in bipolar disorder. | AncΓn I et al. | β | 2011 | β |
| Sex modulates the associations between the COMT gene and personality traits. | Chen C et al. | β | 2011 | β |
| Sources of Cognitive Exploration: Genetic Variation in the Prefrontal Dopamine System Predicts Openness/Intellect. | Deyoung CG et al. | β | 2011 | β |
| The genetics of sex differences in brain and behavior. | Ngun TC et al. | β | 2011 | β |
| Tolcapone, COMT polymorphisms and pharmacogenomic treatment of schizophrenia. | Bitsios P et al. | β | 2011 | β |
| Variants in COMT and DBH influence on response inhibition ability in Chinese Han females. | Gong P et al. | β | 2011 | β |
| A follow-up study: acute behavioural effects of Delta(9)-THC in female heterozygous neuregulin 1 transmembrane domain mutant mice. | Long LE et al. | β | 2010 | β |
| Are genetic variants of COMT associated with addiction? | TammimΓ€ki AE et al. | β | 2010 | β |
| Association of polymorphisms in genes involved in the dopaminergic pathway with blood pressure and uric acid levels in Chinese females. | Yeh TK et al. | β | 2010 | β |
| Association study of a functional catechol-O-methyltransferase polymorphism and smoking in healthy Caucasian subjects. | Nedic G et al. | β | 2010 | β |
| Catechol O-methyltransferase variants and cognitive performance in schizophrenia and bipolar disorder versus controls. | Wirgenes KV et al. | β | 2010 | β |
| Chronic adolescent exposure to Ξ-9-tetrahydrocannabinol in COMT mutant mice: impact on psychosis-related and other phenotypes. | O'Tuathaigh CM et al. | β | 2010 | β |
| Comt1 genotype and expression predicts anxiety and nociceptive sensitivity in inbred strains of mice. | Segall SK et al. | β | 2010 | β |
| COMT val158met influence on electroconvulsive therapy response in major depression. | Domschke K et al. | β | 2010 | β |
| Executive functions and selective attention are favored in middle-aged healthy women carriers of the Val/Val genotype of the catechol-o-methyltransferase gene: a behavioral genetic study. | SolΓs-Ortiz S et al. | β | 2010 | β |
| Gender-specific COMT Val158Met polymorphism association in Spanish schizophrenic patients. | Hoenicka J et al. | β | 2010 | β |
| Gonadectomy and hormone replacement exert region- and enzyme isoform-specific effects on monoamine oxidase and catechol-O-methyltransferase activity in prefrontal cortex and neostriatum of adult male rats. | Meyers B et al. | β | 2010 | β |
| Imaging genetics of mood disorders. | Scharinger C et al. | β | 2010 | β |
| Polymorphisms in catechol-O-methyltransferase and cytochrome p450 subfamily 19 genes predispose towards Madurella mycetomatis-induced mycetoma susceptibility. | van de Sande WW et al. | β | 2010 | β |
| Sex-dependent cognitive phenotype of mice lacking mGluR8. | Duvoisin RM et al. | β | 2010 | β |
| The catechol o-methyltransferase (COMT) val(158)met polymorphism modulates the association of serious life events (SLE) and impulsive aggression in female patients with borderline personality disorder (BPD). | Wagner S et al. | β | 2010 | β |
| The catechol-O-methyl-transferase gene in tardive dyskinesia. | Zai CC et al. | β | 2010 | β |
| The clock gene PER2 and sleep problems: association with alcohol consumption among Swedish adolescents. | Comasco E et al. | β | 2010 | β |
| The effects of gender and catechol O-methyltransferase (COMT) Val108/158Met polymorphism on emotion regulation in velo-cardio-facial syndrome (22q11.2 deletion syndrome): An fMRI study. | Coman IL et al. | β | 2010 | β |
| The role of the rheumatologist in managing pain therapy. | Borenstein D | β | 2010 | β |
| Validation of Serbian version of the disease-specific myasthenia gravis questionnaire. | Basta I et al. | β | 2010 | β |
| Variation in the catechol-O-methyltransferase Val 158 Met polymorphism associated with conduct disorder and ADHD symptoms, among adolescent male delinquents. | DeYoung CG et al. | β | 2010 | β |
| A functional single-nucleotide polymorphism in the catechol-O-methyltransferase gene alter vitiligo risk in a Chinese population. | Li K et al. | β | 2009 | β |
| COMT Val158Met and cognition: main effects and interaction with educational attainment. | Enoch MA et al. | β | 2009 | β |
| Effect of estradiol on striatal dopamine activity of female hemiparkinsonian monkeys. | Morissette M et al. | β | 2009 | β |
| Effects of catechol-O-methyltransferase on normal variation in the cognitive function of children. | Barnett JH et al. | β | 2009 | β |
| Enhanced latent inhibition in dopamine receptor-deficient mice is sex-specific for the D1 but not D2 receptor subtype: implications for antipsychotic drug action. | Bay-Richter C et al. | β | 2009 | β |
| Genes, cognition and brain through a COMT lens. | Dickinson D et al. | β | 2009 | β |
| Genetics of emotion regulation. | Canli T et al. | β | 2009 | β |
| Genetic vulnerability to affective psychopathology in childhood: a combined voxel-based morphometry and functional magnetic resonance imaging study. | Mechelli A et al. | β | 2009 | β |
| Introduction: genes, cognition and neuropsychiatry. | ElvevΓ₯g B et al. | β | 2009 | β |
| Pain and rheumatology: thinking outside the joint. | Clauw DJ et al. | β | 2009 | β |
| Sensorimotor gating depends on polymorphisms of the serotonin-2A receptor and catechol-O-methyltransferase, but not on neuregulin-1 Arg38Gln genotype: a replication study. | Quednow BB et al. | β | 2009 | β |
| Tolcapone effects on gating, working memory, and mood interact with the synonymous catechol-O-methyltransferase rs4818c/g polymorphism. | Roussos P et al. | β | 2009 | β |
| Increase in free choice oral ethanol self-administration in catechol-o-methyltransferase gene-disrupted male mice. | TammimΓ€ki A et al. | β | 2008 | β |
| Phenotypic characterization of cognition and social behavior in mice with heterozygous versus homozygous deletion of catechol-O-methyltransferase. | Babovic D et al. | β | 2008 | β |
| Sex steroid-related candidate genes in psychiatric disorders. | Westberg L et al. | β | 2008 | β |