Haplotype relative risk study of catechol-O-methyltransferase (COMT) and attention deficit hyperactivity disorder (ADHD): Association of the high- enzyme activity val allele with ADHD impulsive-hyperactive phenotype

Jacques Eisenberg, Galit Mei-Tal, Avraham Steinberg, Eduardo Tartakovsky, Ada Zohar, Inga Gritsenko, Lubov Nemanov, Richard P. Ebstein

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151 Scopus citations

Abstract

Attention deficit hyperactivity disorder (ADHD) is a developmental syndrome expressed along three domains: inattention, hyperactive-impulsive, and combined type. Both environmental and genetic factors contribute to the etiology of this complex disease. In the current investigation, a catechol-O- methyltransferase (COMT) polymorphism that codes for a high versus low enzyme COMT activity was examined using family-based methods for a role in ADHD. Using a haplotype relative risk design and a parent-to-proband allele transmission test with 48 ADHD triads, we found an association between COMT and illness (χ2 = 4.72, p = 0.03, df = 1). In particular, the impulsive- hyperactive type of ADHD (excluding inattention) ascertained by Diagnostic and Statistical Manual of Mental Disorders (DSM IV) criteria (χ2 = 8.34, p = 0.004, df = 1), by the Conners Teaching Rating Hyperactivity scale (Pearson χ2 = 5.32, p = 0.02, df = 1) as well as by the Continuous Performance Test False Alarm scale (χ2 = 2.78, p = 0.096, df = 1) were associated with the high enzyme activity COMT val allele. Similar results were obtained if genotype frequencies were compared. It should be noted that the association between the high-enzyme activity COMT val allele that increases CNS dopamine (and norepinephrine) clearance is consistent with the use of methylphenidate, an agent that increases dopamine (and norepinephrine) turnover, in the treatment of this disorder. These provisional findings suggest that newly developed COMT inhibitors such as tolcapone, applied in Parkinson's disease, might in due time be considered in the treatment of ADHD.

Original languageEnglish
Pages (from-to)497-502
Number of pages6
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume88
Issue number5
DOIs
StatePublished - 15 Oct 1999
Externally publishedYes

Keywords

  • Association
  • Attention deficit hyperactivity disorder (ADHD)
  • Catechol-O- methyltransferase (COMT)
  • Complex genetic disease
  • Haplotype relative risk
  • Impulsive
  • Polymorphism

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