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The role of a mineralocorticoid receptor gene functional polymorphism in the symptom dimensions of persistent ADHD

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Abstract

Attention-deficit/hyperactivity disorder (ADHD) affects approximately 5 % of school-aged children and 2.5 % of adults. Genetic studies in ADHD have pointed to genes in different neurobiological systems, with relatively small individual effects. The mineralocorticoid receptor is the main receptor involved in the initial triggering of stress response. Therefore, its encoding gene (NR3C2) is a candidate for psychiatric disorder studies, including ADHD, and behavioral phenotypes. There is evidence that the Val allele of the MRI180V polymorphism (rs5522) increases the risk of depression, attention and cognitive deficits. We investigated the possible role of the mineralocorticoid receptor gene in the symptom dimensions and susceptibility to persistent ADHD. We compared genotype and allele frequencies in 478 adult patients with ADHD and 597 controls and symptom dimensions in 449 patients and 132 controls. Diagnoses were based on the DSM-IV criteria. ADHD symptom dimensions were investigated with SNAP-IV for ADHD severity and Barkley scales for severity and impairment. Carriers of the Val allele presented higher inattention, hyperactivity/impulsivity and impairment scores, while genotype and allele frequencies did not differ between patients and controls. These results are consistent with a possible link between genetic variations in the HPA axis and inattention and hyperactivity measures.

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Acknowledgments

We thank the following Brazilian funding agencies: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Conselho de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo a Pesquisa do Rio Grande do Sul (FAPERGS-DECIT/PPSUS) and Programa de Apoio a Núcleos de Excelência (PRONEX). Our thanks are also due to Stephen Faraone and Benjamin Neale for information and data on GWAS studies in ADHD.

Conflict of interest

Dr Rohde was on the speaker’s bureau and/or acted as consultant for Eli-Lilly, Janssen-Cilag and Novartis in the last 3 years. Currently, his only industry-related activity is taking part in the advisory board/speaker’s bureau for Eli-Lilly and Novartis (less than U$ 10,000 per year and reflecting less than 5 % of his gross income per year). The ADHD Program chaired by him received unrestricted educational and research support from the following pharmaceutical companies in the last 3 years: Abbott, Bristol-Myers Squibb, Eli-Lilly, Janssen-Cilag and Novartis. Dr Belmonte-de-Abreu is on the speaker’s bureau or is a consultant for Janssen-Cilag and Bristol-Myers Squibb. Dr Grevet is on the speaker’s bureau or is a consultant for Novartis, Janssen-Cilag and Shire.

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Authors and Affiliations

  1. Departamento de Genética, Instituto de Biociências, UFRGS, Caixa Postal: 15053, Porto Alegre, RS, CEP 91501-970, Brazil

    Gustavo Lucena Kortmann, Verônica Contini, Guilherme Pinto Bertuzzi, Nina Roth Mota, Diego Luiz Rovaris, Vanessa Rodrigues Paixão-Côrtes, Leandro Leal de Lima & Claiton Henrique Dotto Bau

  2. Laboratório de Perícias, Instituto Geral de Perícias, Porto Alegre, RS, Brazil

    Gustavo Lucena Kortmann

  3. ADHD Program, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil

    Verônica Contini, Guilherme Pinto Bertuzzi, Nina Roth Mota, Diego Luiz Rovaris, Leandro Leal de Lima, Eugenio Horacio Grevet, Carlos Alberto Iglesias Salgado, Eduardo Schneider Vitola, Luis Augusto Rohde, Paulo Belmonte-de-Abreu & Claiton Henrique Dotto Bau

  4. National Institute of Developmental Psychiatry for Children and Adolescents, Porto Alegre, Brazil

    Verônica Contini & Luis Augusto Rohde

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  1. Gustavo Lucena Kortmann
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  2. Verônica Contini
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  9. Carlos Alberto Iglesias Salgado
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Correspondence to Claiton Henrique Dotto Bau.

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Kortmann, G.L., Contini, V., Bertuzzi, G.P. et al. The role of a mineralocorticoid receptor gene functional polymorphism in the symptom dimensions of persistent ADHD. Eur Arch Psychiatry Clin Neurosci 263, 181–188 (2013). https://doi.org/10.1007/s00406-012-0321-z

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