Molecular genetic study of serotonin system genes in attention deficit hyperactivity disorder (ADHD)

grantor: University of TorontoAttention Deficit Hyperactivity Disorder (ADHD) is a childhood disorder marked by persistent patterns of inattention and hyperactivity/impulsivity, causing impairment in academic, social, and emotional development. Several lines of evidence have implicated the serotonergic system in behavioural inhibition and hyperactivity. Furthermore, serotonin exerts a significant degree of regulatory control over dopamine activity, suggesting that an imbalance between the two systems may be responsible for the development of ADHD. We tested for linkage disequilibrium between serotonin system genes (HTR2A, HTR1B, HTR1D, SLC6A4, TPH) and childhood ADHD using the Transmission Disequilibrium Test (TDT). Results revealed preferential transmission of the HTR2A 452Tyr allele to the affected offspring, suggesting linkage disequilibrium of this polymorphism with ADHD. A trend towards linkage disequilibrium of the HTR1B G861C polymorphism with ADHD was noted which may be of paternal origin. A quantitative TDT (QTDT) analysis revealed no evidence for linkage disequilibrium between the HTR2A and HTR1B, receptor genes and the continuous hyperactive/impulsive or inattention symptom dimensions of ADHD. These findings are suggestive for a serotonin component to ADHD pathophysiology that may open new doors towards a multi-system theory in ADHD genetics research.M.Sc