%0 Journal Article
%A del Campo, Natalia
%A Fryer, Tim D
%A Hong, Young T
%A Smith, Rob
%A Brichard, Laurent
%A Acosta-Cabronero, Julio
%A Chamberlain, Samuel R
%A Tait, Roger
%A Izquierdo, David
%A Regenthal, Ralf
%A Dowson, Jonathan
%A Suckling, John
%A Baron, Jean-Claude
%A Aigbirhio, Franklin I
%A Robbins, Trevor W
%A Sahakian, Barbara J
%A Müller, Ulrich
%T A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment.
%J Brain
%V 136
%N 11
%@ 1460-2156
%C Oxford
%I Oxford Univ. Press
%M DZNE-2020-03419
%P 3252-3270
%D 2013
%X Through the combined use of (18)F-fallypride positron emission tomography and magnetic resonance imaging this study examined the neural mechanisms underlying the attentional deficits associated with attention deficit/hyperactivity disorder and their potential reversal with a single therapeutic dose of methylphenidate. Sixteen adult patients with attention deficit/hyperactivity disorder and 16 matched healthy control subjects were positron emission tomography and magnetic resonance imaging scanned and tested on a computerized sustained attention task after oral methylphenidate (0.5 mg/kg) and placebo administration in a within-subject, double-blind, cross-over design. Although patients with attention deficit/hyperactivity disorder as a group showed significant attentional deficits and reduced grey matter volume in fronto-striato-cerebellar and limbic networks, they had equivalent D2/D3 receptor availability and equivalent increases in endogenous dopamine after methylphenidate treatment to that observed in healthy control subjects. However, poor attentional performers drawn from both the attention deficit/hyperactivity disorder and the control groups had significantly reduced left caudate dopamine activity. Methylphenidate significantly increased dopamine levels in all nigro-striatal regions, thereby normalizing dopamine levels in the left caudate in low performers. Behaviourally, methylphenidate improved sustained attention in a baseline performance-dependent manner, irrespective of diagnosis. This finding was accompanied by an equally performance-dependent effect of the drug on dopamine release in the midbrain, whereby low performers showed reduced dopamine release in this region. Collectively, these findings support a dimensional model of attentional deficits and underlying nigro-striatal dopaminergic mechanisms of attention deficit/hyperactivity disorder that extends into the healthy population. Moreover, they confer midbrain dopamine autoreceptors a hitherto neglected role in the therapeutic effects of oral methylphenidate in attention deficit/hyperactivity disorder. The absence of significant case-control differences in D2/D3 receptor availability (despite the observed relationships between dopamine activity and attention) suggests that dopamine dysregulation per se is unlikely to be the primary cause underlying attention deficit/hyperactivity disorder pathology in adults. This conclusion is reinforced by evidence of neuroanatomical changes in the same set of patients with attention deficit/hyperactivity disorder.
%K Adult
%K Attention Deficit Disorder with Hyperactivity: drug therapy
%K Attention Deficit Disorder with Hyperactivity: metabolism
%K Attention Deficit Disorder with Hyperactivity: pathology
%K Attention Deficit Disorder with Hyperactivity: physiopathology
%K Benzamides
%K Corpus Striatum: drug effects
%K Corpus Striatum: metabolism
%K Corpus Striatum: pathology
%K Corpus Striatum: physiopathology
%K Cross-Over Studies
%K Dopamine Uptake Inhibitors: administration & dosage
%K Dopamine Uptake Inhibitors: pharmacology
%K Double-Blind Method
%K Fluorodeoxyglucose F18
%K Humans
%K Magnetic Resonance Imaging: instrumentation
%K Magnetic Resonance Imaging: methods
%K Male
%K Mesencephalon: drug effects
%K Mesencephalon: metabolism
%K Mesencephalon: pathology
%K Mesencephalon: physiopathology
%K Methylphenidate: administration & dosage
%K Methylphenidate: pharmacology
%K Multimodal Imaging: instrumentation
%K Multimodal Imaging: methods
%K Positron-Emission Tomography: instrumentation
%K Positron-Emission Tomography: methods
%K Psychiatric Status Rating Scales
%K Radiopharmaceuticals
%K Young Adult
%K Benzamides (NLM Chemicals)
%K Dopamine Uptake Inhibitors (NLM Chemicals)
%K Radiopharmaceuticals (NLM Chemicals)
%K Fluorodeoxyglucose F18 (NLM Chemicals)
%K Methylphenidate (NLM Chemicals)
%K fallypride (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:24163364
%2 pmc:PMC4125626
%R 10.1093/brain/awt263
%U https://pub.dzne.de/record/137097