Catechol-O-methyltransferase (COMT): a gene contributing to sex differences in brain function, and to sexual dimorphism in the predisposition to psychiatric disorders
- PMID: 17805313
- DOI: 10.1038/sj.npp.1301543
Catechol-O-methyltransferase (COMT): a gene contributing to sex differences in brain function, and to sexual dimorphism in the predisposition to psychiatric disorders
Abstract
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.
Similar articles
-
Importance of the COMT gene for sex differences in brain function and predisposition to psychiatric disorders.Curr Top Behav Neurosci. 2011;8:119-40. doi: 10.1007/7854_2010_97. Curr Top Behav Neurosci. 2011. PMID: 21769726 Review.
-
Influence of catechol-O-methyltransferase Val158Met polymorphism on neuropsychological and functional outcomes of classical rehabilitation and cognitive remediation in schizophrenia.Neurosci Lett. 2007 May 7;417(3):271-4. doi: 10.1016/j.neulet.2007.02.076. Epub 2007 Mar 2. Neurosci Lett. 2007. PMID: 17383818
-
Catechol-O-methyltransferase, dopamine, and sleep-wake regulation.Sleep Med Rev. 2015 Aug;22:47-53. doi: 10.1016/j.smrv.2014.10.006. Epub 2014 Oct 27. Sleep Med Rev. 2015. PMID: 25466290 Review.
-
COMT Val(158)Met genotype determines the direction of cognitive effects produced by catechol-O-methyltransferase inhibition.Biol Psychiatry. 2012 Mar 15;71(6):538-44. doi: 10.1016/j.biopsych.2011.12.023. Biol Psychiatry. 2012. PMID: 22364739 Free PMC article. Clinical Trial.
-
Catechol-O-methyltransferase gene and obsessive-compulsive symptoms in patients with recent-onset schizophrenia: preliminary results.Psychiatry Res. 2008 Jan 15;157(1-3):1-8. doi: 10.1016/j.psychres.2007.02.001. Epub 2007 Sep 12. Psychiatry Res. 2008. PMID: 17850881
Cited by
-
Tripeptidyl peptidase II coordinates the homeostasis of calcium and lipids in the central nervous system and its depletion causes presenile dementia in female mice through calcium/lipid dyshomeostasis-induced autophagic degradation of CYP19A1.Theranostics. 2024 Jan 27;14(4):1390-1429. doi: 10.7150/thno.92571. eCollection 2024. Theranostics. 2024. PMID: 38389851 Free PMC article.
-
Epigenetics as a target to mitigate excess stroke risk in people of African ancestry: A scoping review.J Stroke Cerebrovasc Dis. 2024 May;33(5):107585. doi: 10.1016/j.jstrokecerebrovasdis.2024.107585. Epub 2024 Jan 20. J Stroke Cerebrovasc Dis. 2024. PMID: 38253246 Review.
-
To Each His Own Fear: Gender-Related Association of Anxiety, Substance Use, and Eating Disorders in a Representative Birth Cohort Sample of Young Adults with Either COMT Val158Met allele.Neuropsychobiology. 2024;83(1):41-48. doi: 10.1159/000535912. Epub 2024 Jan 16. Neuropsychobiology. 2024. PMID: 38228118 Free PMC article.
-
Association Between the rs4680 Polymorphism of the COMT Gene and Personality Traits among Combat Sports Athletes.J Hum Kinet. 2023 Jul 6;89:89-99. doi: 10.5114/jhk/168789. eCollection 2023 Oct. J Hum Kinet. 2023. PMID: 38053955 Free PMC article.
-
Genotypic and Haplotypic Association of Catechol-O-Methyltransferase rs4680 and rs4818 Gene Polymorphisms with Particular Clinical Symptoms in Schizophrenia.Genes (Basel). 2023 Jun 27;14(7):1358. doi: 10.3390/genes14071358. Genes (Basel). 2023. PMID: 37510262 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Miscellaneous