Attention deficit hyperactivity disorder (ADHD) is a highly heritable and heterogeneous disorder, which usually be-comes 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. 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 multicentre 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 HTR1B5-HT1B in the total sample (for HHRR; Chi square = 7.4, P -0.0065 and TDT; (Chi square = 6.7, P = 0.01). Analysis of HT2A 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 (Chi square -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.
|Number of pages
|American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
|Published - 8 Oct 2001