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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)

Molecular Psychiatry volume 7, pages 626–632 (2002)Cite this article

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 (χ2 = 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 (χ2 = 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 χ2 = 7.94, P = 0.047). Similarly results were obtained when 19 female probands were compared to female controls (genotype χ2 = 21.28; P = 0.0032, 3 df and allele χ2 = 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.

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Acknowledgements

This research was supported by a grant from the Israeli Ministry of Health.

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Authors and Affiliations

  1. Geha Mental Health Center, Petak Tikvah, Israel

    I Manor & S Tyano

  2. Research Laboratory, S Herzog Memorial Hospital, Jerusalem, Israel

    E Mel, J Eisenberg, R Bachner-Melman & R P Ebstein

  3. Child Psychiatry Clinic, S Herzog Memorial Hospital, Jerusalem, Israel

    M Kotler

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Correspondence to R P Ebstein.

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Beersheva Mental Health Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Israel

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Manor, I., Tyano, S., Mel, E. et al. 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). Mol Psychiatry 7, 626–632 (2002). https://doi.org/10.1038/sj.mp.4001037

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