title: The dopamine transporter haplotype and reward-related striatal responses in adult ADHD.
abstract: Attention deficit/hyperactivity disorder (ADHD) is a highly heritable disorder and several genes increasing disease risk have been identified. The dopamine transporter gene, SLC6A3/DAT1, has been studied most extensively in ADHD research. Interestingly, a different haplotype of this gene (formed by genetic variants in the 3' untranslated region and intron 8) is associated with childhood ADHD (haplotype 10-6) and adult ADHD (haplotype 9-6). The expression of DAT1 is highest in striatal regions in the brain. This part of the brain is of interest to ADHD because of its role in reward processing is altered in ADHD patients; ADHD patients display decreased striatal activation during reward processing. To better understand how the DAT1 gene exerts effects on ADHD, we studied the effect of this gene on reward-related brain functioning in the area of its highest expression in the brain, the striatum, using functional magnetic resonance imaging. In doing so, we tried to resolve inconsistencies observed in previous studies of healthy individuals and ADHD-affected children. In a sample of 87 adult ADHD patients and 77 healthy comparison subjects, we confirmed the association of the 9-6 haplotype with adult ADHD. Striatal hypoactivation during the reward anticipation phase of a monetary incentive delay task in ADHD patients was again shown, but no significant effects of DAT1 on striatal activity were found. Although the importance of the DAT1 haplotype as a risk factor for adult ADHD was again demonstrated in this study, the mechanism by which this gene increases disease risk remains largely unknown.
authors: Department of Psychiatry, Radboud University Nijmegen Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
authors: Martine
authors: M
authors: Hoogman
authors: Marten
authors: M
authors: Onnink
authors: Roshan
authors: R
authors: Cools
authors: Esther
authors: E
authors: Aarts
authors: Cornelis
authors: C
authors: Kan
authors: Alejandro
authors: A
authors: Arias Vasquez
authors: Jan
authors: J
authors: Buitelaar
authors: Barbara
authors: B
authors: Franke
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009426:Netherlands; D009474:Neurons / Q000378:metabolism*; D015203:Reproducibility of Results; D012201:Reward; D009435:Synaptic Transmission; D020080:Tandem Repeat Sequences
chemical_list: D020413:3' Untranslated Regions; D050483:Dopamine Plasma Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human