Because of its role in catecholamine metabolism and several lines of evidence pointing to a locus for psychosis near the COMT gene on chromosome 22q11, we have analysed the COMT Val158Met polymorphism as a candidate susceptibility factor for bipolar affective disorder.
One of these is its biochemical function in metabolism of catecholamine neurotransmitters; another is the microdeletion, on chromosome 22q11, that includes the COMT gene and causes velocardiofacial syndrome, a syndrome associated with a high rate of psychosis, particularly schizophrenia.
This indicates that COMT genotype is a heritable aspect of dopamine regulation and it further explicates the mechanism by which the COMT valine allele increases susceptibility for psychosis.
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.
As COMT and PRODH are both located on chromosome 22q11, the results also argue against the hypothesis that schizophrenia is associated with a decrease in expression of all 22q11 genes, as had been suggested by the high prevalence of psychosis in people with hemizygous 22q11 deletions.
These findings suggest that COMT polymorphism influences on the risk of psychosis since the early stages, and claims for the possibility to identify distinct phenotypes on genetic basis among AD patients.
New evidence of association between COMT gene and prefrontal neurocognitive function in healthy individuals from sibling pairs discordant for psychosis.
A functional polymorphism in the catechol-O-methyltransferase (COMT) gene moderated the influence of adolescent cannabis use on developing adult psychosis.
The main objective of the study was to determine if COMT genetic variation is associated with risk of psychosis in AD, and included a case-control study of 373 individuals diagnosed with AD with, or without, psychosis.
Experimental effects of Delta-9-THC on cognition and psychosis are moderated by COMTVal(158)Met genotype, but the effects may in part be conditional on the additional presence of pre-existing psychosis liability.
The COMT gene lies in a chromosomal region of interest for psychosis and bipolar spectrum disorder and a common polymorphism within the gene alters the activity of the enzyme.
These results confirm the role of COMT genotype in the cognition of patients under treatment for psychosis, suggesting that it influences the extent of their cognitive deterioration.
Thus we review recent contributions of neuroimaging and electrophysiological as well as genetic studies: which new diagnostic perspectives offer endophenotypes (such as P300, P50 sensory gating, MMN, smooth pursuit eye movements; indicating a specific genetic vulnerability) together with a better understanding of schizophrenic pathophysiology (state-dependent biological markers, e.g. aggravated motor neurological soft signs during psychosis) in prodromal schizophrenia when still ambiguous clinical symptoms are present.Several examples (e.g. from COMT polymorphisms to working memory deficits) illustrate more specific underlying neuronal mechanisms behind behavioural symptoms.
COMT genetic variation seems to be involved in the psychotic symptomatology of the schizophrenia-spectrum disorders and specifically in the narrow schizophrenia phenotype.
Catechol-O-methyltransferase (COMT) regulates dopamine degradation and is located in a genomic region that is deleted in a syndrome associated with psychosis, making it a promising candidate gene for schizophrenia.
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.
In addition, carriers of the COMTVal(158)Met Val allele were more susceptible to the effect of stress on the psychosis outcome than those with the Met/Met genotype (test for interaction: chi2 = 5.02, df = 1, p = 0.025).
Preliminary evidence suggests that polymorphisms within the catechol-O-methyltransferase and brain-derived neurotrophic factor genes may interact with psychosocial stress in the development of psychosis; however, extensive further investigations are required to confirm this.