Aggressive, violent, and dangerous behavior associated with a polymorphism determining high and low catechol O-methyltransferase (COMT) activity

I. Gritsenko, M. Kotler, H. Cohen, I. E. Averbuch, A. Grinshpoon, R. P. Ebstein

Research output: Contribution to journalArticlepeer-review


Although aggressive, violent, and dangerous behavior (AVD) in humans has multifactorial causes, genetic factors are estimated by twin and adoption studies to substantially contribute to the development of such conduct. Recently, homozygosity of a low enzyme-activity variant of the catechol o-methyltransferase (COMT) gene was reported to be associated with aggressive behavior in a small group of schizophrenic patients. We have now confirmed and extended this finding in a larger group (n = 135) of mostly schizophrenic patients, some of whom were confined to a maximum-security psychiatric facility for AVD (n = 31) and homicidal (n = 42) behavior. Significant differences were observed in the distribution of COMT genotypes between AVD, homicidal, and schizophrenic patients at low risk for violent behavior (likelihood ratio: Χ2 = 20.3, P < 0.001, df = 4). This difference was also validated across ethnic categories. The association between the COMT polymorphism and AVD and homicidal behavior was also present in a small group (n = 10) of retarded subjects, suggesting that the connection between COMT and violence is of wider significance. As previously reported, no difference in the distribution of COMT geno-types was observed between low-risk schizophrenic patients and controls. No association was observed between AVD and homicidal behaviors and the dopamine D4 exon III repeat length (D4DR) polymorphism and the serotonin transporter promoter region polymorphism (5-HTTLPR). The currently reported verification of a link between COMT and violent human behavior further strengthens the role of specific genetic factors in the mediation of antisocial and criminal actions and, since serotonin is not a substrate for COMT, suggests the involvement of nonserotonergic pathways such as dopamine and norepinephrine in such behaviors.

Original languageEnglish
Pages (from-to)516-517
Number of pages2
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Issue number6
StatePublished - 6 Nov 1998
Externally publishedYes


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