Abstract
Attention deficit hyperactivity disorder (ADHD) is a highly heritable and heterogeneous disorder, which usually becomes apparent during the first few years of childhood. Imbalance in dopamine neurotransmission has been suggested as a factor predisposing to ADHD. However, evidence has suggested an interaction between dopamine and serotonin systems in the pathophysiology of the disorder. Studies using selective agonists of the different 5-HT receptors microinjected into selected brain structures have shown a positive modulating effect on the functional activities of the mesotelencephalic dopaminergic system. This suggests that some of the genetic predisposition to ADHD might be due to DNA variation at serotonin system genes. In this study, we investigated polymorphisms in HTR1B and HTR2A (which encode the serotonin receptors 5-HT1B and 5-HT2A respectively) in a European ADHD sample. Using haplotype based haplotype relative risk (HHRR) and transmission disequilibrium test (TDT) analyses, we observed significant preferential transmission of the allele 861G of the HTR1B in the total sample (for HHRR; χ2 = 7.4, P = 0.0065 and TDT; (χ2 = 6.4, P = 0.014). Analysis of HTR2A failed to reveal evidence of association or linkage between the His452Tyr polymorphism and ADHD in the total sample. However, a significantly increased transmission of the allele 452His was observed in the Irish sample alone (χ2 = 4.9, P = 0.026). These preliminary data suggest an important role for the serotonin system in the development of ADHD. Further studies, preferentially including different ethnic groups are required to substantiate these findings.
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Acknowledgements
We would like to acknowledge the generous support of the Health Research Board, Dublin, The Wellcome Trust (ZH and AK), and the Hyperactive and Attention Disorder (HAD) Group Ireland. The London group is supported by the MRC. SC and LK are Wellcome Trust Research Fellows. The Cardiff group is also supported by Wellcome and Action Research. Thanks are also due to Jane Holmes and Tracey Heyer who were involved in the first wave of sample collection at Manchester. We would also like to thank the families who participated in the study.
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Hawi, Z., Dring, M., Kirley, A. et al. Serotonergic system and attention deficit hyperactivity disorder (ADHD): a potential susceptibility locus at the 5-HT1B receptor gene in 273 nuclear families from a multi-centre sample. Mol Psychiatry 7, 718–725 (2002). https://doi.org/10.1038/sj.mp.4001048
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DOI: https://doi.org/10.1038/sj.mp.4001048
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