Catechol-O-methyltransferase (COMT): a gene contributing to sex differences in brain function, and to sexual dimorphism in the predisposition to psychiatric disorders.
Catechol O-methyltransferase (COMT) has been associated with aggression, attention deficit/hyperactivity disorder (ADHD), and other psychiatric disorders.
COMT is a known neuropsychiatric candidate gene, which contains a genotype variant (Val<sup>108/158</sup>Met) that affects protein function and has been found associated with several psychiatric disorders.
Catechol-O-methyltransferase (COMT) is one of the major mammalian enzymes involved in the metabolic degradation of catecholamines and is considered a candidate for several psychiatric disorders and symptoms, including the psychopathology associated with the 22q11 microdeletion syndrome.
A common functional polymorphism that results in a three- to four-fold difference in catechol-O-methyltransferase (COMT) enzyme activity has been related to psychiatric disorders such as ultra-ultra rapid cycling bipolar disorder, drug abuse and alcoholism (Lachman et al., 1996a; Karayiorgou et al., 1997; Vandenbergh et al., 1997; Papolos et al., 1998; Tiihonen et al., 1999).
A variation in catechol-O-methyltransferase (COMT) gene (Val(108/158)Met) affects the physiological response of hippocampal-prefrontal circuits, predicts variation in human memory and is associated with increased risk for psychiatric disorders.
Additionally, these findings contribute to the growing literature on sex-specific effects of COMT on the predisposition to psychiatric disorders and personality traits.
Although a polymorphism in this gene, COMTVal(158)Met, affects human behavior in response to stress little is known about its effect on dopaminergic activity associated with the human stress response, which may be of interest for stress-related psychiatric disorders such as psychosis.
Among the genes in the deleted region, catechol-O-methyltransferase (COMT) has a particular relevance for psychiatric disorders: lower COMT enzymatic activity decreases the clearance of dopamine (DA), yielding higher levels of catecholamines in the central nervous system.
Further research with larger samples is needed to explore the interactions of the COMT gene rs4680 polymorphism and sex and psychiatric disorders on suicide attempts.
Further studies are required to better understand the association of symptomatology of schizophrenia and other psychiatric disorders with COMT gene polymorphism.
Future longitudinal studies focusing on additional COMT polymorphic sites and other candidate genes from the deleted region will elucidate the molecular pathways leading to schizophrenia and other psychiatric disorders in VCFS.
High COMT activity in women with depression is apparent mainly in patients whose first and second degree relatives revealed psychiatric disturbances, particularly affective disorders.
Many association studies have reported associations between the catechol-O-methyltransferase (COMT) gene and psychiatric disorders including major depression (MDD).
Many clinical and genomic association studies suggested that the catechol-O-methyltransferase (COMT) gene region was an important genetic locus for psychiatric disorders, because of the proposed relationship between its function in catecholaminergic neurotransmission and individual response to antidepressants, and vulnerability to psychiatric disorders.
Of special interest is the role of this gene in major psychoses especially since a microdeletion (22q11) containing the COMT gene (velo-cardio-facial syndrome) also carries with it several types of behavioral disorders, including an increased prevalence of schizophrenia.
On the other hand, preferential transmission of COMTrs4680 A allele and A-A haplotype (P<0.05) was observed specifically in male IID probands without any behavioral problem.
One hundred eighty-one AD patients and 208 age-matched controls underwent clinical and neuropsychological examination, behavioural and psychiatric disturbances evaluation, and ApoE and COMT genotyping.
One of its most widely studied variations comprises a common single nucleotide polymorphism (SNP), a valine-to-methionine substitution at codon 158 (COMTVal158Met), which has been associated with various cognitive phenotypes, psychiatric disorders and changes in brain activation and structure.