Family-based and association studies of monoamine oxidase A and attention deficit hyperactivity disorder (ADHD): Preferential transmission of the long promoter-region repeat and its association with impaired performance on a continuous performance test (TOVA)

I. Manor, S. Tyano, E. Mel, J. Eisenberg, R. Bachner-Melman, M. Kotler, R. P. Ebstein

Research output: Contribution to journalArticlepeer-review

Abstract

Monoamine oxidase A (MAO A) is located on the X chromosome and metabolizes biogenic amines including dopamine, norepinephrine and serotonin. A functional promoter-region polymorphism of this gene has been described that has been studied in a number of mental illnesses but not in attention deficit hyperactivity disorder (ADHD). In the current study, we examined the MAO A promoter-region polymorphism initially in 133 triads and observed preferential transmission of the long alleles from 74 heterozygote mothers to ADHD probands (X2 = 4.37, P = 0.036, df = 1). We also examined the role of this polymorphism in a computerized continuous performance test, the TOVA. Significant differences were observed on errors of commission (X2 = 7.021, P = 0.008) and patients carrying the long MAO A allele made significantly more such errors. Errors of commission are a measure of impulsivity. However, following Ritalin (methylphenidate) administration the association between this polymorphism and errors of commission was markedly attenuated and no longer significant at the P < 0.05 level. We also analyzed the provisional association by the case-control design. A significant difference in allele frequency was observed between 110 male probands vs 202 male controls (Pearson X2 = 7.94, P = 0.047). Similarly results were obtained when 19 female probands were compared to female controls (genotype X2 = 21.28; P = 0.0032, 3 df and allele X2 = 30.88, P = 0.0007, 2 df). All three complementary approaches employed (family-based, case-control and quantitative trait design) suggest a role for the MAO A promoter-region polymorphism in conferring risk for ADHD in our patient population.

Original languageEnglish
Pages (from-to)626-632
Number of pages7
JournalMolecular Psychiatry
Volume7
Issue number6
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Association
  • Attention deficit hyperactivity disorder (ADHD)
  • Complex genetic
  • Continuous performance test
  • Endophenotype
  • Monoamine oxidase A
  • Neuropsychological functioning
  • Polymorphism
  • Promoter
  • QTL
  • TOVA
  • Transmission disequilibrium test

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