J Psychiatry Neurosci 2016;41(6):405-412
Glaucia C. Akutagava-Martins, PhD; Angelica Salatino-Oliveira, PhD; Christian Kieling, MD, PhD; Julia P. Genro, PhD; Guilherme V. Polanczyk, MD, PhD; Luciana Anselmi, PhD; Ana M.B. Menezes, MD, PhD; Helen Gonçalves, PhD; Fernando C. Wehrmeister, PhD; Fernando C. Barros, MD, PhD; Sidia M. Callegari-Jacques, PhD; Luis A. Rohde, MD, PhD; Mara H. Hutz, PhD
Background: Attention-deficit/hyperactivity disorder (ADHD) symptoms are dimensionally distributed in the population. This study aimed to assess the role of the catechol-O-methyltransferase (COMT) and of the dopamine transporter (DAT1) genes on ADHD symptoms in the general population.
Methods: We investigated 4101 individuals from the 1993 Pelotas Birth Cohort Study using the parent version of the Strengths and Difficulties Questionnaire (SDQ) at ages 11 and 15 years. The SDQ hyperactivity/inattention scores were the main outcomes.
Results: Linear regression analyses demonstrated that the increasing number of COMT158Val and DAT1 10R alleles significantly predicted increasing SDQ hyperactivity/inattention scores in boys at both 11 and 15 years of age (β coefficient = 0.049, t = 2.189, p = 0.029, R2 = 0.012, and β coefficient = 0.064, t = 2.832, p = 0.005, R2 = 0.008, respectively). The presence of both COMT158Val and DAT1 10R alleles was also associated with full categorical ADHD diagnosis at 18 years of age in boys (χ2 = 4.561, p = 0.033, odds ratio 2.473, 95% confidence interval 1.048–5.838) from this cohort. We did not observe these associations in girls.
Limitations: Our analyses of SDQ hyperactivity/inattention scores were not corrected for SDQ scores of conduct problems because these variables were highly correlated.
Conclusion: This study demonstrates a role for COMT and DAT1 genes on hyperactivity/inattention symptoms and provides further support for ADHD as the extreme of traits that vary in the population. It also confirms previous evidence for sexual dimorphism on COMT and DAT1 gene expression.
Submitted Aug. 6, 2015; Revised Jan. 19, 2016; Revised Jan. 29, 2016; Revised Feb. 25, 2016; Accepted Mar. 28, 2016; Early-released June 23, 2016
Acknowledgements: This article is based on data from the study “Pelotas Birth Cohort, 1993” conducted by the Postgraduate Program in Epidemiology at Universidade Federal de Pelotas. The 1993 Birth Cohort Study is currently supported by the Wellcome Trust through the program entitled Major Awards for Latin America on Health Consequences of Population Change. The European Union, National Support Program for Centers of Excellence (PRONEX), the Brazilian National Research Council (CNPq), and the Brazilian Ministry of Health supported previous phases of the study. The Brazilian National Research Council (CNPq) also supported the laboratory work. The sponsors of the study had no role in the design or conduct of this study; in the collection, management, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript.
Affiliations: From the Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Akutagava-Martins, Salatino-Oliveira, Genro, Hutz); the Child and Adolescent Psychiatry Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil (Kieling, Rohde); the Department of Psychiatry, Universidade de São Paulo, São Paulo, São Paulo, Brazil (Polanczyk); the Graduate Program in Epidemiology, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Anselmi, Menezes, Gonçalves, Wehrmeister, Barros); the Graduate Program in Health and Behavior, Universidade Católica de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Barros); the Department of Statistics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Callegari-Jacques); and the Institute for Developmental Psychiatry for Children and Adolescents (INCT-CNPq), Brazil (Polanczyk, Rohde).
Competing interests: C. Kieling has received support from Brazilian governmental research funding agencies (Conselho Nacional de Desenvolvimento Científico e Tecnológico [CNPq], Coordenação de Aperfeiçoamento de Pessoal de Nível Superior [CAPES], and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul [FAPERGS]). He also receives authorship royalties from Artmed and Manole. G. Polanczyk reports grants from CNPq, the São Paulo Research Foundation (FAPESP), Fundação Maria Cecilia Souto Vidigal, and Grand Challenges Canada; and personal fees from the Bill & Melinda Gates Foundation, Editora Manole, Shire, Teva and Johnson & Johnson, outside the submitted work. L. Rohde reports grants and personal fees from Janssen-Cilag, Novartis and Shire; personal fees from Eli-Lilly; and royalties from Oxford Press and Artmed Editora, outside the submitted work. No other competing interests declared.
Contributors: G. Akutagava-Martins, C. Kieling, Polanczyk, L. Rohde and M. Hutz designed the study. A. Salatino-Oliveira, J. Genro, L. Anselmi, A. Menezes, H. Gonçalves, F. Wehrmeister and F. Barros acquired the data, which G. Akutagava-Martins, C. Kieling, G. Polanczyk, S. Callegari-Jacques, L. Rohde and M. Hutz analyzed. G. Akutagava-Martins and M. Hutz wrote the article, which all authors reviewed and approved for publication.
Correspondence to: M.H. Hutz, Universidade Federal do Rio Grande do Sul, Departamento de Genética, Caixa postal, RS, Brazil; email@example.com