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Serotonergic system and attention deficit hyperactivity disorder (ADHD): a potential susceptibility locus at the 5-HT(1B) receptor gene in 273 nuclear families from a multi-centre sample

Hawi, Z., Dring, M., Kirley, A., Foley, D., Kent, L., Craddock, N., Asherson, P., Curran, S., Gould, A., Richards, S., Lawson, D., Pay, H., Turic, D., Langley, K., Owens, M., O’Donovan, M., Thapar, A., Fitzgerald, M. and Gill, M. (2002) Serotonergic system and attention deficit hyperactivity disorder (ADHD): a potential susceptibility locus at the 5-HT(1B) receptor gene in 273 nuclear families from a multi-centre sample Molecular Psychiatry, 7, (7), pp. 718-725. (doi:10.1038/sj.mp.4001048).

Record type: Article

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; 2 = 7.4, P = 0.0065 and TDT; (2 = 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 (2 = 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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More information

Published date: 2002
Keywords: 5-HTR(1B) 5-HTR(2A), attention deficit hyperactivity disorder (ADHD), haplotype based haplotype relative risk (HHRR), transmission disequilibrium test (TDT)

Identifiers

Local EPrints ID: 148333
URI: http://eprints.soton.ac.uk/id/eprint/148333
ISSN: 1359-4184
PURE UUID: 78fa1a42-292f-4c6f-8ef0-54a5f1f43584

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Date deposited: 08 Jul 2010 14:20
Last modified: 18 Jul 2017 19:32

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Contributors

Author: Z. Hawi
Author: M. Dring
Author: A. Kirley
Author: D. Foley
Author: L. Kent
Author: N. Craddock
Author: P. Asherson
Author: S. Curran
Author: A. Gould
Author: S. Richards
Author: D. Lawson
Author: H. Pay
Author: D. Turic
Author: K. Langley
Author: M. Owens
Author: M. O’Donovan
Author: A. Thapar
Author: M. Fitzgerald
Author: M. Gill

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