Aggressive behaviour in patients with schizophrenia is associated with catechol-O-methyltransferase genotype

Abstract

The high-activity homozygotes showed significantly higher scores of aggression, whereas the heterozygotes showed significantly lower scores. The odds ratio for aggression for the high-activity homozygotes was 2.07 (95% Cl=1.03-4.15), whereas that for the heterozygotes was 0.54 (95% Cl=0.30-1.00). CONCLUSIONS; The high-activity COMT homozygote confers a higher risk of recorded aggression in schizophrenia. Heterozygotes had a significantly lower risk, which may represent an example of heterosis/heterozygote advantage.

Estudo de revisão dos fatores biológicos, sociais e ambientais associados com o comportamento agressivo

“…[12][13][14][15][16][17][18][19][20][21][22][23] Of these, eight had adopted a prospective longitudinal study design, 12,14,15,18,19,[21][22][23] three were case-control studies 16,17,20 and one was a transversal study. Six studies related aggressive behavior to genic expression.…”

“…Six studies related aggressive behavior to genic expression. [12][13][14][15][16][17] Two demonstrated the genic expression of the serotonin transporter, 13,14 one demonstrated the genic expression of the monoaminaoxidase (MAOA), 12 another study demonstrated the genic expression of the transporter and the receptor of dopamine, 15 and two studies presented the genic expression of the catechol-O-methyltransferase enzyme (COMT). 16,17 Four studies related aggressive behavior to maternal exposure to psychoactive substances.…”

“…[12][13][14][15][16][17] Two demonstrated the genic expression of the serotonin transporter, 13,14 one demonstrated the genic expression of the monoaminaoxidase (MAOA), 12 another study demonstrated the genic expression of the transporter and the receptor of dopamine, 15 and two studies presented the genic expression of the catechol-O-methyltransferase enzyme (COMT). 16,17 Four studies related aggressive behavior to maternal exposure to psychoactive substances. [18][19][20][21] Two other studies showed evidence that the use of tobacco during pregnancy constitutes an important risk factor, 18,19 while one study demonstrated the role played by alcohol in this interaction.…”

“…In a population of 353 individuals of which 180 suffered from schizophrenia and 173 were controls, Jones et al observed that patients who were homozygous for the polymorphism that determines the low activity level of the COMT gene presented significantly higher aggressiveness scores (OR = 2.07) when compared to heterozygous patients (OR = 0.54). 16 While also studying a population of schizophrenic patients who had committed homicide (n = 30), compared to nonviolent schizophrenics (n = 62) and to a control group (n = 415) with regards to the presence of the valine or methionine alleles, 17 Kotler et al did not find a statistically significant difference between non-violent schizophrenics and the control group, although in the homicidal schizophrenics, the frequency of the low activity COMT genotype (p = 0.087) was higher. The presence of the methionine allele is related to the gene's low activity which, in turn, is associated with a higher risk for the development of aggressive and antisocial behavior.…”

Catechol-O-methyl transferase Val158Met gene polymorphism in schizophrenia: working memory, frontal lobe MRI morphology and frontal cerebral blood flow

“…The methionine allele has been associated with aggression, suicide, worse prognosis and greater positive symptom severity in schizophrenia. 91,[96][97][98][99][100] Egan et al's finding of an association between the valine allele and poor WCST performance has generated renewed interest in this area of investigation, especially with regard to the effects of COMT in mediating cognition in schizophrenia. 52 This finding has been replicated in part by Joober et al, who found that genotype effects on WCST performance among schizophrenia patients was at a trend level of significance, and was nonsignificant in healthy volunteers.…”