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Aggressive behavior in schizophrenia is associated with the low enzyme activity COMT polymorphism: a replication

Rael D Strous1, Karen A Nolan, Raya Lapidus

  • 1Beer Yaakov Mental Health Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics
|June 20, 2003
PubMed
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The catechol O-methyltransferase (COMT) gene

Area of Science:

  • Neurogenetics
  • Psychiatric Disorders
  • Behavioral Science

Background:

  • Previous research suggests a link between a specific COMT gene polymorphism (codon 158) and aggressive behavior in schizophrenia patients.
  • Replication of these findings has been inconsistent, necessitating further investigation into potential statistical or methodological factors.
  • Understanding genetic contributions to aggression in schizophrenia is crucial for personalized treatment approaches.

Purpose of the Study:

  • To investigate the association between the COMT 158 polymorphism and aggressive behavior in patients with schizophrenia (SZ).
  • To examine the role of the monoamine oxidase A (MAOA) gene promoter polymorphism in aggressive behavior within the same patient cohort.
  • To clarify the relationship between COMT genotype and specific facets of aggression, including self-directed and outward aggression.

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Main Methods:

  • Schizophrenia patients were assessed for violent behavior using the Lifetime History of Aggression (LHA) scale, encompassing aggression, self-directed aggression, and consequences/antisocial behavior subscales.
  • DNA was collected and genotyped for the COMT 158 polymorphism and a functional polymorphism in the MAOA gene promoter.
  • Statistical analyses were performed to determine the association between genetic variations and LHA scores.

Main Results:

  • A statistically significant association was observed between aggressive behavior in schizophrenia and the COMT 158 polymorphism (F(2,105) = 5.616, P = 0.005).
  • Individuals homozygous for the 158Met variant of the COMT gene, associated with low enzyme activity, exhibited higher mean LHA scores.
  • The association was primarily driven by elevated scores on the Aggression and Self-Directed Aggression subscales, not the Consequences/Antisocial Behavior subscale. No significant association was found for the MAOA gene.

Conclusions:

  • The catechol O-methyltransferase (COMT) gene polymorphism at codon 158 is significantly associated with aggressive behavior in schizophrenia patients.
  • The COMT 158Met variant, linked to reduced enzyme activity, correlates with increased outward and self-directed aggression.
  • These findings reinforce the role of COMT as a modifying gene influencing interindividual variability in aggressive tendencies within the schizophrenic population.