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Exploration of 19 serotoninergic candidate genes in adults and children with attention-deficit/hyperactivity disorder identifies association for 5HT2A, DDC and MAOB

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder in which different genetic and environmental susceptibility factors are involved. Several lines of evidence support the view that at least 30% of ADHD patients diagnosed in childhood continue to suffer the disorder during adulthood and that genetic risk factors may play an essential role in the persistence of the disorder throughout lifespan. Genetic, biochemical and pharmacological studies support the idea that the serotonin system participates in the etiology of ADHD. Based on these data, we aimed to analyze single nucleotide polymorphisms across 19 genes involved in the serotoninergic neurotransmission in a clinical sample of 451 ADHD patients (188 adults and 263 children) and 400 controls using a population-based association study. Several significant associations were found after correcting for multiple testing: (1) the DDC gene was strongly associated with both adulthood (P=0.00053; odds ratio (OR)=2.17) and childhood ADHD (P=0.0017; OR=1.90); (2) the MAOB gene was found specifically associated in the adult ADHD sample (P=0.0029; OR=1.90) and (3) the 5HT2A gene showed evidence of association only with the combined ADHD subtype both in adults (P=0.0036; OR=1.63) and children (P=0.0084; OR=1.49). Our data support the contribution of the serotoninergic system in the genetic predisposition to ADHD, identifying common childhood and adulthood ADHD susceptibility factors, associations that are specific to ADHD subtypes and one variant potentially involved in the continuity of the disorder throughout lifespan.

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Acknowledgements

We are grateful to patients and controls for their participation in the study, to Sergi Valero, Marta Pascual and Juan Ramón González for their helpful comments on statistical aspects of the article, to Alfons Macaya and Pere Antoni Soler-Insa for their support, to Roser Corominas, Ester Cuenca, Lucas Brunso, Anna Puig, Anna Carreras and Carles Arribas for technical assistance, to Mariana Nogueira, Carlos Cordovilla, Marisa Joga and Monserrat Jiménez for their participation in the clinical assessment and to Banc de Sang i Teixits Hospital (Vall d'Hebron) for their collaboration in the recruitment of controls. MB and MR are recipients of a Ramon y Cajal and a Juan de la Cierva contracts from ‘Ministerio de Ciencia y Tecnología’, respectively. Financial support was received from ‘Instituto de Salud Carlos III-FIS’ (PI041267, PI042010, PI040524). SNP genotyping services were provided by the Spanish ‘Centro Nacional de Genotipado’ (CEGEN; www.cegen.org).

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Ribasés, M., Ramos-Quiroga, J., Hervás, A. et al. Exploration of 19 serotoninergic candidate genes in adults and children with attention-deficit/hyperactivity disorder identifies association for 5HT2A, DDC and MAOB. Mol Psychiatry 14, 71–85 (2009). https://doi.org/10.1038/sj.mp.4002100

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