Homicidal behavior in schizophrenia associated with a genetic polymorphism determining low catechol O-methyltransferase (COMT) activity.
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 chi(2) = 10.53, P = 0.005, df = 2). No difference in COMT genotype was found between 62 nonviolent 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 directly 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 nonviolent schizophrenic patients (chi(2) = 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 (chi(2) = 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). Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:628-633, 1999.
Kotler
M
M
Beersheva Mental Health Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheva, Israel.
Barak
P
P
Cohen
H
H
Averbuch
I E
IE
Grinshpoon
A
A
Gritsenko
I
I
Nemanov
L
L
Ebstein
R P
RP
D000328:Adult; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005787:Gene Frequency; D006708:Homicide / Q000523:psychology*; D006720:Homozygote; D006801:Humans; D007585:Jews / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D026901:Membrane Transport Proteins; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics; D050638:Receptors, Dopamine D4; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D012559:Schizophrenia / Q000201:enzymology / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins; D012727:Sex Characteristics; D014754:Violence / Q000523:psychology
D002352:Carrier Proteins; C493599:DRD4 protein, human; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017448:Receptors, Dopamine D2; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D050638:Receptors, Dopamine D4; D008715:Methionine; D002394:Catechol O-Methyltransferase