Homicidal behavior in schizophrenia associated with a genetic polymorphismdetermining low catechol O-methyltransferase (COMT) activity

Although aggressive, violent, and dangerous behavior in man has multifactor ial causes, genetic factors are estimated by twin and adoption studies to s ubstantially contribute to the development of such conduct. Recently, homoz ygosity of a low enzyme activity variant of the catechol O-methyltransferas e (COMT) gene was reported to be associated with aggressive behavior in a g roup of schizophrenic patients. We observe a similar tendency in a group of 80 schizophrenic patients who were confined to a maximum-security psychiat ric facility for homicide. Significant excess (46.7% versus 21.0%) homozygo sity of the low activity COMTmet/met genotype was observed in 30 mostly mal e (28 of 30) homicidal schizophrenic patients compared with 415 control sub jects (Pearson chi(2) = 10.53, P = 0.005, df = 2). No difference in COMT ge notype was found between 62 non-violent schizophrenic patients and the 415 control subjects (chi(2) = 0.963, P > 0.1, df = 2). A trend for excess (46. 7% versus 25.8%) homozygosity of the low activity COMTmet/met genotype was also observed when the homicidal schizophrenic subjects were compared direc tly with the nonviolent schizophrenic patients (chi(2) = 4.03, P = 0.1, df = 2). Similarly, an excess of the low activity COMTmet allele was observed in homicidal versus non-violent schizophrenic patients (chi(2) = 2.92, P = 0.087, df = 2). Similar results were obtained if only male subjects were ex amined. No significant difference was found between control (257 Ashkenazi and 152 non-Ashkenazi Jews) COMT genotypes in the two principal ethnic grou ps examined (chi(2) = 3.79, P > 0.1, df = 2), Finally, no association was o bserved between homicidal behavior in schizophrenic patients and the dopami ne D4 exon III repeat length polymorphism (D4DR) and the serotonin transpor ter promoter-region polymorphism (5-HTTLPR). Am. J. Med. Genet. (Neuropsych iatr. Genet.) 88:628-633, 1999. (C) 1999 Wiley-Liss, Inc.