ABSTRACT
Attention deficit hyperactivity disorder (ADHD) is a common behavioral disorder affecting children and adults. It has been suggested that gene variants related to serotonin neurotransmission are associated with ADHD. We tested the functional promoter polymorphism 5-HTTLPR and seven single nucleotide polymorphisms in SLC6A4 for association with ADHD in 448 adult ADHD patients and 580 controls from Norway. Replication attempts were performed in a sample of 1454 Caucasian adult ADHD patients and 1302 controls from Germany, Spain, the Netherlands and USA, and a meta-analysis was performed also including a previously published adult ADHD study. We found an association between ADHD and rs140700 [odds ratio (OR ) = 0.67; P = 0.01] and the short (S) allele of the 5-HTTLPR (OR = 1.19; P = 0.06) in the Norwegian sample. Analysis of a possible gender effect suggested that the association might be restricted to females (rs140700: OR = 0.45; P = 0.00084). However, the meta-analysis of 1894 cases and 1878 controls could not confirm the association for rs140700 [OR = 0.85, 95% confidence interval (CI) = 0.67-1.09; P = 0.20]. For 5-HTTLPR, five of six samples showed a slight overrepresentation of the S allele in patients, but meta-analysis refuted a strong effect (OR = 1.10, 95% CI = 1.00-1.21; P = 0.06). Neither marker showed any evidence of differential effects for ADHD subtype, gender or symptoms of depression/anxiety. In conclusion, our results do not support a major role for SLC6A4 common variants in persistent ADHD, although a modest effect of the 5-HTTLPR and a role for rare variants cannot be excluded.
Subject(s)
Attention Deficit Disorder with Hyperactivity/genetics , Genetic Association Studies , Serotonin Plasma Membrane Transport Proteins/genetics , Adolescent , Adult , Age Factors , Anxiety Disorders/complications , Attention Deficit Disorder with Hyperactivity/classification , Attention Deficit Disorder with Hyperactivity/complications , Case-Control Studies , Depressive Disorder/complications , Female , Genetic Predisposition to Disease , Germany , Humans , Male , Netherlands , Norway , Polymorphism, Single Nucleotide , Reference Values , Sex Factors , Spain , United States , Young AdultABSTRACT
Evidence-based treatments for attention-deficit hyperactivity disorder (ADHD) in children include primarily medication (stimulants and atomoxetine) and psychosocial interventions (parent training and behavioural classroom interventions). Results of treatment studies suggest that ADHD without significant coexisting disorders can be treated effectively by pharmacotherapy and expert counselling, while additional behaviour therapy demonstrates no significant improvement. Incremental benefits of combined pharmacological and behavioural interventions emerge if a comorbid condition is present. Behaviour therapy alone may be useful for treating less pronounced ADHD symptoms. Therapeutic strategies also account for the specific treatment of comorbid disorders and the need for support by youth welfare services.
