Attention deficit hyperactivity disorder.
Attention deficit hyperactivity disorder (ADHD) is a behavioral diagnosis based on the presence of developmentally inappropriate levels of impulsivity, overactivity, and inattentiveness. It is a familial condition with a complex pattern of inheritance. Variation of several genes involved in the regulation of dopamine, norepinephrine, and serotonin neurotransmission is associated with ADHD. We highlight the two most prominent findings with the dopamine D4 receptor (DRD4) gene and the dopamine transporter (DAT1) gene, and their implications for the understanding of the cellular and neurobiological basis for ADHD. Cognitive and functional studies using electrophysiology and brain imaging frequently indicate altered processing in ADHD during performance on cognitive tasks hypothesized to measure a "core" deficit, such as response inhibition. Yet, children with ADHD appear to suffer from a more general deficit, including impairment in attentional alerting, orienting, response preparation, and control. Reward processes are also altered and, further, a strong association emerges with intraindividual variability, with several causal hypotheses being proposed. Task performance correlates with underactivation of, especially, frontostriatal areas of the brain, but an extended network of brain regions is also implicated. Electroencephalography studies indicate abnormalities in ADHD in relation to slow-wave activity, linked to underarousal. These advances in the areas of genetics, cognitive function, neurophysiology, and neuroanatomy of ADHD give important leads for interdisciplinary research that aims to delineate the causal pathways. Such research is only at its beginning, but is illustrated by recent findings of an association between DAT1 and increased response variability in ADHD.
Kuntsi
Jonna
J
MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK. j.kuntsi@iop.kcl.ac.uk
McLoughlin
Gráinne
G
Asherson
Philip
P
D001289:Attention Deficit Disorder with Hyperactivity / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D004569:Electroencephalography; D006801:Humans; D007175:Impulsive Behavior / Q000503:physiopathology; D009638:Norepinephrine / Q000378:metabolism; D050638:Receptors, Dopamine D4 / Q000235:genetics* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism
C493599:DRD4 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; D050638:Receptors, Dopamine D4; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine