Aggressive behaviour in patients with schizophrenia is associated with catechol-O-methyltransferase genotype (original) (raw)
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Psychiatry research, 1997
We have recently characterized a functional polymorphism in the catechol-O-methyltransferase (COMT) gene that is responsible for substantial variability in COMT enzymatic activity found in humans. A common low-activity variant of the enzyme contains a methionine residue at amino acid 158 of membrane-bound COMT whereas the common high activity variant has a valine at this site. Considering the role of COMT in dopamine metabolism and the involvement of dopaminergic pathways in the pathogenesis of schizophrenia and violence, we screened 37 patients with schizophrenia to determine whether or not a behavioral association with the COMT polymorphism exists. Patients were assessed for dangerousness on the basis of a history of violent and threatening behavior, crime, cocaine and alcohol abuse, and other antisocial behaviors. We found that schizophrenic patients who were homozygous for the low activity allele were judged by their psychiatrists to be at higher risk for aggressive and dangerou...
European Neuropsychopharmacology, 2008
We examined the association between the Catechol-O-methyltransferase (COMT) Val158Met polymorphism and aggressive schizophrenia. The sample included 61 aggressive schizophrenic patients as well as 104 non-aggressive patients from psychiatric hospitals and 415 healthy volunteers in South Korea. In the case-control comparisons, there was no significant association between the aggressive schizophrenic patients and the COMT Val158Met polymorphism. Looking only at the subgroup of aggressive schizophrenic patients, however, we found a dose-dependent relationship between the Met allele and verbal aggression. In this subgroup, the Met carriers showed a higher verbal aggression score than those with the Val/Val homozygote. These findings support the hypothesized moderating role of the COMT gene in the aggressive behaviour in some schizophrenic patients, though they do not support the existence of a direct association between the COMT Val158Met polymorphism and aggressive schizophrenia case status in the Korean population.
A Meta-Analysis of the Val158Met COMT Polymorphism and Violent Behavior in Schizophrenia
PLoS ONE, 2012
We conducted a meta-analysis of studies examining the association between the Val158Met COMT polymorphism and violence against others in schizophrenia. A systematic search current to November 1, 2011 was conducted using MEDLINE, EMBASE, CINAHL, PsycINFO, ProQuest, and the National Criminal Justice Reference Service and identified 15 studies comprising 2,370 individuals with schizophrenia for inclusion. Bivariate analyses of study sensitivities and specificities were conducted. This methodology allowed for the calculation of pooled diagnostic odds ratios (DOR). Evidence of a significant association between the presence of a Met allele and violence was found such that men's violence risk increased by approximately 50% for those with at least one Met allele compared with homozygous Val individuals (DOR = 1.45; 95% CI = 1.05-2.00; z = 2.37, p = 0.02). No significant association between the presence of a Met allele and violence was found for women or when outcome was restricted to homicide. We conclude that male schizophrenia patients who carry the low activity Met allele in the COMT gene are at a modestly elevated risk of violence. This finding has potential implications for the pharmacogenetics of violent behavior in schizophrenia.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2008
A new functional single nucleotide polymorphism (SNP) Ala72Ser in the COMT gene was discovered recently. The purpose of our study is to examine the association between Ala72Ser and Val158Met functional polymorphisms in COMT gene and homicidal behavior in schizophrenia. DNA was genotyped for the Ala72Ser and Val158Met SNPs of the COMT gene in a sample of 93 schizophrenic patients who committed homicide (H-SCZ) and 100 schizophrenic patients who had never committed homicide (NH-SCZ). A statistically significant difference was found in genotype distribution and allele frequencies in SNP Ala72-Ser of COMT gene between H-SCZ and NH-SCZ group. In haplotype analysis, the frequency of the combination of high-high activity allele (Ala-Val) was lower in H-SCZ group than in NH-SCZ group (P ¼ 0.000069). Our study showed a highly significant association between a COMT haplotype of two functional SNPs and aggressive behavior in schizophrenia.
Suicidal behavior in patients with schizophrenia is related to COMT polymorphism
Psychiatric Genetics, 2000
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). Several studies have also reported associations between the allele encoding the low enzyme activity COMT variant (L allele) and other-directed aggression (Strous et al., 1997; Lachman et al., 1998; Kotler et al., 1999) in schizophrenic and schizoaffective patients. The current study investigated whether the COMT L allele is also associated with suicide attempts in schizophrenic and schizoaffective patients. COMT genotypes were determined and history of suicide attempts was retrospectively investigated in a Finnish sample (n = 94) and a US sample (n = 54). Significant associations were observed between COMT genotype and suicide; specifically, history of violent suicide attempts. The COMT L allele was more frequent in subjects who had attempted suicide by violent means. These associations were significant in males but not females. These findings support a common neurobiological substrate for self- and other-directed aggression, and suggest that catecholaminergic alterations may contribute to these behaviors in schizophrenic and schizoaffective patients.
Molecular Brain Research, 2004
Schizophrenia is a complex disorder with a polygenic inheritance. Catechol-O-methyltransferase (COMT) plays a significant role in the regulation of dopaminergic systems. A polymorphism at COMT Val108/158Met has been identified in association with schizophrenia. We examined the allele and genotype association of the COMT Val108/158Met polymorphism of 297 unrelated schizophrenic patients who strictly met DSM-IV criteria for schizophrenia, and 341 healthy controls. We found significant difference in allele and genotype frequencies between schizophrenic patients and controls (v 2 =13.030; P=0.001). The allele frequency of the COMT-L was 45.79% in the total schizophrenic patients, and 41.50% in controls. The genotype frequency of the COM-LL was 21.2% in the total schizophrenic patients, and 11.4% in controls (OR=2.085; 95% CI=1.350-3.219; v 2 =11.293; P=0.001). With a separate sex analysis, the frequency of the COMT-L allele was moderately distributed in male schizophrenia (v 2 =6.177; df=2; P=0.046). The COMT-LL genotype had a 1.818-fold increased risk for schizophrenia (OR=1.818; 95% CI=1.010-3.273; v 2 =4.048; P=0.044). The frequency of the COMT-L allele was even more significantly distributed in women schizophrenia (v 2 =7.797; df=2; P=0.020). The COMT-LL genotype had remarkably more increased risk for schizophrenia (OR=2.456; 95% CI=1.287-4.687; v 2 =7.710; P=0.005). In conclusion, our results provide strong evidence for a role of the COMT-L allele and LL genotype in the etiopathophysiology of schizophrenia with a sexual difference. D
The Pharmacogenomics Journal, 2007
Genetic variation in the catechol-O-methyltransferase (COMT) gene may influence the susceptibility to schizophrenia and the response to neuroleptic treatment. The authors tested for an association between a COMT haplotype and schizophrenia-spectrum disorders and for an eventual influence of a specific COMT genotype in the clinical outcome and in the response to treatment. The genotypes for single nucleotide polymorphisms rs737865, rs4633, rs6267, rs4680 (Val 158 Met) and rs165599 were determined in 207 patients with schizophrenia-spectrum disorders and 204 paired controls. Statistical tests for linkage disequilibrium and for case-control differences in haplotype frequencies were performed using log-linear modelling embedded within the expectation-maximization algorithm. P-values based on permutations were calculated using the software UNPHASED, and odds ratios were estimated using the SHEsis platform. The response to neuroleptic treatment was assessed by the Global Assessment of Functioning scale and the severity of psychotic symptoms by the positive and negative syndrome scale (PANSS) scale. The overall disease status was significantly associated with the T-G (Val) diplotype for rs4633-rs4680 (P ¼ 0.0049). A significant association was observed between schizophrenia, but not other related disorders, and genotypes GG (Val/Val) for rs4680 and TT for rs4633. Val/Val patients with schizophrenia showed a higher severity of the psychotic symptoms and a worse response to the neuroleptic treatment. COMT genetic variation seems to be involved in the psychotic symptomatology of the schizophreniaspectrum disorders and specifically in the narrow schizophrenia phenotype. Our results show an influence of the Val 158 Met polymorphism on the severity of psychotic symptoms and on the response to treatment.