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The association between the catechol-O-methyltransferase Val108/158Met polymorphism and hyperactive–impulsive and inattentive symptoms in youth

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Abstract

Rationale

Hyperactivity, impulsivity, and inattention are major symptoms occurring in attention-deficit/hyperactivity disorder. This disorder is highly heritable, multifactorial, polygenic, and associated primarily with dysfunctions of dopaminergic, noradrenergic, and serotonergic systems.

Objectives

The present study tested the possible association of the catechol-O-methyltransferase (COMT) Val108/158Met (rs4680) polymorphism with hyperactive–impulsive and inattentive symptoms in male youth.

Method

Polymorphism COMT Val108/158Met was analyzed in 807 male unrelated Caucasian young subjects: 231 healthy controls, 195 subjects with moderate hyperactive symptoms and 254 subjects with moderate inattentive symptoms, 111 subjects with severe hyperactive symptoms and 90 subjects with severe inattentive symptoms, all evaluated using Swanson, Nolan, and Pelham Questionnaire IV criteria.

Results

The frequency of the COMT genotypes, alleles, and the homozygous Met/Met genotype versus Val carriers (χ 2 test with standardized residuals) differed significantly between subjects without and subjects with hyperactive–impulsive and inattentive symptoms. In addition, significantly higher hyperactive–impulsive and inattentive scores were found in subjects with the Met/Met genotype compared to carriers of other COMT genotypes. These significant results were due to the more frequent occurrence of Met/Met genotype or the Met allele in subjects with moderate and severe hyperactive–impulsive and inattentive symptoms compared to matched controls.

Conclusion

These results suggest that the Met/Met genotype or the Met allele of the COMT Val108/158Met, contributing to higher dopaminergic activity, are significantly overrepresented in subjects with moderate or severe hyperactive–impulsive and inattentive symptoms, and that this polymorphism is significantly associated with hyperactive–impulsive and inattentive symptoms in young boys and adolescents.

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Acknowledgments

The authors are grateful to all patients and controls for their participation in the study. This study was supported by the Croatian Ministry of Science, Education and Sport, grant numbers 098-0982522-2455, 098-0982522-2457, the Estonian Science Foundation (no. 8607), the Estonian Ministry of Education and Science (no. 0180027), and the European Social Fund (Estonian Primus grant no. 3–8.2/60).

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Authors declare no conflict of interest.

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Correspondence to Nela Pivac.

Additional information

Matea Nikolac Perkovic and Evelyn Kiive equally contributed to this work.

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Nikolac Perkovic, M., Kiive, E., Nedic Erjavec, G. et al. The association between the catechol-O-methyltransferase Val108/158Met polymorphism and hyperactive–impulsive and inattentive symptoms in youth. Psychopharmacology 230, 69–76 (2013). https://doi.org/10.1007/s00213-013-3138-1

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  • DOI: https://doi.org/10.1007/s00213-013-3138-1

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