Journal Article

DZNE-2020-03419

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment.

del Campo, N. (Corresponding author) ; Fryer, T. D. ; Hong, Y. T. ; Smith, R. ; Brichard, L. ; Acosta-Cabronero, J.DZNE* ; Chamberlain, S. R. ; Tait, R. ; Izquierdo, D. ; Regenthal, R. ; Dowson, J. ; Suckling, J. ; Baron, J.-C. ; Aigbirhio, F. I. ; Robbins, T. W. ; Sahakian, B. J. ; Müller, U.

2013
Oxford Univ. Press Oxford

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Please use a persistent id in citations: doi:10.1093/brain/awt263

Abstract: 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.

Keyword(s): Adult (MeSH) ; Attention Deficit Disorder with Hyperactivity: drug therapy (MeSH) ; Attention Deficit Disorder with Hyperactivity: metabolism (MeSH) ; Attention Deficit Disorder with Hyperactivity: pathology (MeSH) ; Attention Deficit Disorder with Hyperactivity: physiopathology (MeSH) ; Benzamides (MeSH) ; Corpus Striatum: drug effects (MeSH) ; Corpus Striatum: metabolism (MeSH) ; Corpus Striatum: pathology (MeSH) ; Corpus Striatum: physiopathology (MeSH) ; Cross-Over Studies (MeSH) ; Dopamine Uptake Inhibitors: administration & dosage (MeSH) ; Dopamine Uptake Inhibitors: pharmacology (MeSH) ; Double-Blind Method (MeSH) ; Fluorodeoxyglucose F18 (MeSH) ; Humans (MeSH) ; Magnetic Resonance Imaging: instrumentation (MeSH) ; Magnetic Resonance Imaging: methods (MeSH) ; Male (MeSH) ; Mesencephalon: drug effects (MeSH) ; Mesencephalon: metabolism (MeSH) ; Mesencephalon: pathology (MeSH) ; Mesencephalon: physiopathology (MeSH) ; Methylphenidate: administration & dosage (MeSH) ; Methylphenidate: pharmacology (MeSH) ; Multimodal Imaging: instrumentation (MeSH) ; Multimodal Imaging: methods (MeSH) ; Positron-Emission Tomography: instrumentation (MeSH) ; Positron-Emission Tomography: methods (MeSH) ; Psychiatric Status Rating Scales (MeSH) ; Radiopharmaceuticals (MeSH) ; Young Adult (MeSH) ; Benzamides ; Dopamine Uptake Inhibitors ; Radiopharmaceuticals ; Fluorodeoxyglucose F18 ; Methylphenidate ; fallypride

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Contributing Institute(s):

1. Cognitive Neurology and Neurodegeneration (AG Nestor)

Research Program(s):

1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2013

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 10 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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