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A recent study demonstrated that treatment of hyperactive mice with psychostimulants and serotonergic agents produced a calming effect that was dependent on serotonergic neurotransmission and was not associated with any changes in extracellular dopamine levels. 1 The complex interaction between the serotonergic and dopaminergic neurotransmitter systems suggests that a balance between the two systems may be necessary for mediating hyperactive behaviour. Defects in serotonin system genes, therefore, may disrupt normal brain serotonin function causing an imbalance between these neurotransmitter systems leading to the development of attention deficit hyperactivity disorder (ADHD). Attention deficit hyperactivity disorder (ADHD) is a common childhood disruptive behavioral disorder affecting between 3-5% of school age children who display persistent patterns of inattention and hyperactivity/impulsivity causing impairment in academic, social, and emotional development. 2 ADHD children frequently exhibit a variety of other comorbid conditions such as learning disorder, mood disorder, and other disruptive behavior disorders including oppositional defiant disorder (ODD) and conduct disorder (CD).While the exact mechanisms for the disorder are unknown, research has suggested abnormalities in the catecholaminergic and serotonergic systems. Support for a catecholaminergic hypothesis has been based on evidence from neuroimaging studies which have suggested reduced functioning in frontal-striatal regions, whose pathways are rich in catecholamines, notably dopamine. 3 Furthermore, stimulant medications, such as methylphenidate (Ritalin™), whose primary site of action is the dopamine transporter, have shown widespread clinical success in the treatment of ADHD. The significant interaction between the dopaminergic and serotonergic systems, 4 however, suggests that dopamine dysfunction may not be the sole basis for the development of ADHD.Evidence for the serotonergic hypothesis began two decades ago when it was found that whole blood and serum serotonin (5-HT) concentrations were decreased in children with ADHD. 5,6 These results have been further supported by a recent study that also found a tendency towards low platelet serotonin in a sample of children with severe ADHD. 7 Additional support for a serotonin hypothesis is demonstrated by the moderate efficacy of several serotonin enhancing agents in the treatment of ADHD including selective serotonin reuptake inhibitors (SSRIs) 8 and certain selective monoamine oxidase inhibitors. 9 Several lines of evidence have indicated abnormal serotonergic function in children with disruptive behaviour disorders (ADHD, ODD, CD) who display marked problems with hyperactivity, impulsivity, and aggression. [10][11][12][13][14] Animal models of ADHD have also been useful in implicating a role for serotonin in the control of attention, impulsivity, and hyperactivity. Rodents that had poorer performance on a task measuring attention and impulsivity had a greater index of serotonin utilization in t...

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Serotonin plays an essential role in cognition, locomotor activity, and the regulation of sleep, pain, mood, and aggression. Polymorphisms of the HTR1B gene have been implicated in a variety of psychiatric disorders including attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). The objectives of this study were to: (i) expand our original investigation of the relationship between the HTR1B receptor gene and attention deficit/ hyperactivity and; (ii) to investigate a possible association of obsessive behaviors/perfectionism and the HTR1B gene in a sample of 203 families with an ADHD proband. Six single nucleotide polymorphisms (SNPs) of the HTR1B receptor gene were genotyped using standard methods. Evidence for an association between the HTR1B gene and ADHD as a qualitative diagnosis, or the inattentive and hyperactive-impulsive quantitative traits was not supported by either TDT single marker analysis or haplotype analysis. In addition we did not find evidence to suggest an association between HTR1B and perfectionism in this sample of ADHD families. INTRODUCTIONBoth attention-deficit/hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD) are common neuropsychiatric disorders. ADHD has an estimated prevalence of 3%-5% of school-age children [Cantwell, 1996] and OCD is estimated to affect 2%-3% children and adolescents [Geller et al., 1998]. The co-occurrence of ADHD and OCD is not unusual in clinical populations. ADHD-like symptoms are seen in as many as 30% of youths with OCD [Geller et al., 2002] A recent publication reported obsessive-compulsive behaviors and increased perfectionism in 11% of school-age children diagnosed with ADHD [Arnold et al., 2005]. Evidence from family and twin studies suggests that genetic factors play a major role in the etiology of both ADHD and OCD [Thapar et al., 1999;Nestadt et al., 2000]. However, to date, there have not been any published articles examining possible shared genetic influences between ADHD and OCD.Serotonergic mechanisms have been implicated in the pathophysiology of ADHD and there is evidence supporting the notion that serotonin plays a mediator role in the hyperactive and impulsive behaviors associated with ADHD [Gainetdinov et al., 1999;Quist and Kennedy, 2001]. Serotonin became a leading target for investigation of the neurobiology of OCD largely due to the remarkable therapeutic effects of serotonin re-uptake inhibitors on obsessions and compulsions [Greist et al., 1995;Swinson et al., 1998] and the suggestion that there is a relationship between pre-treatment levels of the cerebro-spinal fluid metabolites of serotonin (i.e., 5-hydroxyindolacetic acid, homovanillic acid) and clinical response to medication targeting serotonin re-uptake [Baumgarten and Grozdanovic, 1998].Evidence for HTR1B as a susceptibility gene in ADHD was suggested in several independent studies that found preferential transmission of the ''G ''allele of the rs6296 (C861G, HincII) single nucleotide polymorphism (SNP) of the HTR1B gene in A...