TY  - JOUR
AU  - del Campo, Natalia
AU  - Fryer, Tim D
AU  - Hong, Young T
AU  - Smith, Rob
AU  - Brichard, Laurent
AU  - Acosta-Cabronero, Julio
AU  - Chamberlain, Samuel R
AU  - Tait, Roger
AU  - Izquierdo, David
AU  - Regenthal, Ralf
AU  - Dowson, Jonathan
AU  - Suckling, John
AU  - Baron, Jean-Claude
AU  - Aigbirhio, Franklin I
AU  - Robbins, Trevor W
AU  - Sahakian, Barbara J
AU  - Müller, Ulrich
TI  - A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment.
JO  - Brain
VL  - 136
IS  - 11
SN  - 1460-2156
CY  - Oxford
PB  - Oxford Univ. Press
M1  - DZNE-2020-03419
SP  - 3252-3270
PY  - 2013
AB  - 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.
KW  - Adult
KW  - Attention Deficit Disorder with Hyperactivity: drug therapy
KW  - Attention Deficit Disorder with Hyperactivity: metabolism
KW  - Attention Deficit Disorder with Hyperactivity: pathology
KW  - Attention Deficit Disorder with Hyperactivity: physiopathology
KW  - Benzamides
KW  - Corpus Striatum: drug effects
KW  - Corpus Striatum: metabolism
KW  - Corpus Striatum: pathology
KW  - Corpus Striatum: physiopathology
KW  - Cross-Over Studies
KW  - Dopamine Uptake Inhibitors: administration & dosage
KW  - Dopamine Uptake Inhibitors: pharmacology
KW  - Double-Blind Method
KW  - Fluorodeoxyglucose F18
KW  - Humans
KW  - Magnetic Resonance Imaging: instrumentation
KW  - Magnetic Resonance Imaging: methods
KW  - Male
KW  - Mesencephalon: drug effects
KW  - Mesencephalon: metabolism
KW  - Mesencephalon: pathology
KW  - Mesencephalon: physiopathology
KW  - Methylphenidate: administration & dosage
KW  - Methylphenidate: pharmacology
KW  - Multimodal Imaging: instrumentation
KW  - Multimodal Imaging: methods
KW  - Positron-Emission Tomography: instrumentation
KW  - Positron-Emission Tomography: methods
KW  - Psychiatric Status Rating Scales
KW  - Radiopharmaceuticals
KW  - Young Adult
KW  - Benzamides (NLM Chemicals)
KW  - Dopamine Uptake Inhibitors (NLM Chemicals)
KW  - Radiopharmaceuticals (NLM Chemicals)
KW  - Fluorodeoxyglucose F18 (NLM Chemicals)
KW  - Methylphenidate (NLM Chemicals)
KW  - fallypride (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:24163364
C2  - pmc:PMC4125626
DO  - DOI:10.1093/brain/awt263
UR  - https://pub.dzne.de/record/137097
ER  -