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

Moshe Kotler, Peretz Barak, Hagit Cohen, Ilya E. Averbuch, Alexander Grinshpoon, Inga Gritsenko, Lubov Nemanov, Richard P. Ebstein*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

170 Scopus citations

Abstract

Although aggressive, violent, and dangerous behavior in man 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 group of schizophrenic patients. We observe a similar tendency in a group of 30 schizophrenic patients who were confined to a maximum- security psychiatric facility for homicide. Significant excess (46.7% versus 21.0%) homozygosity of the low activity COMTmet/met genotype was observed in 30 mostly male (28 of 30) homicidal schizophrenic patients compared with 415 control subjects (Pearson χ2 = 10.53, P = 0.005, df = 2). No difference in COMT genotype was found between 62 nonviolent schizophrenic patients and the 415 control subjects (χ2 = 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 directly with the nonviolent schizophrenic patients (χ2 = 4.03, P = 0.1, df = 2). Similarly, an excess of the low activity COMTmet allele was observed in homicidal versus nonviolent schizophrenic patients (χ2 = 2.92, P = 0.087, df = 2). Similar results were obtained if only male subjects were examined. No significant difference was found between control (257 Ashkenazi and 152 non-Ashkenazi Jews) COMT genotypes in the two principal ethnic groups examined (χ2 = 3.79, P > 0.1, df = 2). Finally, no association was observed between homicidal behavior in schizophrenic patients and the dopamine D4 exon III repeat length polymorphism (D4DR) and the serotonin transporter promoter- region polymorphism (5-HTTLPR).

Original languageEnglish
Pages (from-to)628-633
Number of pages6
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume88
Issue number6
DOIs
StatePublished - 15 Dec 1999
Externally publishedYes

Keywords

  • Aggression
  • Catechol O- methyltransferase
  • Dopamine D4 receptor
  • Genetic polymorphism
  • Schizophrenia
  • Serotonin transporter promoter

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