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000137097 1001_ $$0P:(DE-HGF)0$$adel Campo, Natalia$$b0$$eCorresponding author
000137097 245__ $$aA positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment.
000137097 260__ $$aOxford$$bOxford Univ. Press$$c2013
000137097 264_1 $$2Crossref$$3online$$bOxford University Press (OUP)$$c2013-10-25
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000137097 520__ $$aThrough 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.
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000137097 650_7 $$2NLM Chemicals$$aBenzamides
000137097 650_7 $$2NLM Chemicals$$aDopamine Uptake Inhibitors
000137097 650_7 $$2NLM Chemicals$$aRadiopharmaceuticals
000137097 650_7 $$00Z5B2CJX4D$$2NLM Chemicals$$aFluorodeoxyglucose F18
000137097 650_7 $$0207ZZ9QZ49$$2NLM Chemicals$$aMethylphenidate
000137097 650_7 $$0G9FWZ369GX$$2NLM Chemicals$$afallypride
000137097 650_2 $$2MeSH$$aAdult
000137097 650_2 $$2MeSH$$aAttention Deficit Disorder with Hyperactivity: drug therapy
000137097 650_2 $$2MeSH$$aAttention Deficit Disorder with Hyperactivity: metabolism
000137097 650_2 $$2MeSH$$aAttention Deficit Disorder with Hyperactivity: pathology
000137097 650_2 $$2MeSH$$aAttention Deficit Disorder with Hyperactivity: physiopathology
000137097 650_2 $$2MeSH$$aBenzamides
000137097 650_2 $$2MeSH$$aCorpus Striatum: drug effects
000137097 650_2 $$2MeSH$$aCorpus Striatum: metabolism
000137097 650_2 $$2MeSH$$aCorpus Striatum: pathology
000137097 650_2 $$2MeSH$$aCorpus Striatum: physiopathology
000137097 650_2 $$2MeSH$$aCross-Over Studies
000137097 650_2 $$2MeSH$$aDopamine Uptake Inhibitors: administration & dosage
000137097 650_2 $$2MeSH$$aDopamine Uptake Inhibitors: pharmacology
000137097 650_2 $$2MeSH$$aDouble-Blind Method
000137097 650_2 $$2MeSH$$aFluorodeoxyglucose F18
000137097 650_2 $$2MeSH$$aHumans
000137097 650_2 $$2MeSH$$aMagnetic Resonance Imaging: instrumentation
000137097 650_2 $$2MeSH$$aMagnetic Resonance Imaging: methods
000137097 650_2 $$2MeSH$$aMale
000137097 650_2 $$2MeSH$$aMesencephalon: drug effects
000137097 650_2 $$2MeSH$$aMesencephalon: metabolism
000137097 650_2 $$2MeSH$$aMesencephalon: pathology
000137097 650_2 $$2MeSH$$aMesencephalon: physiopathology
000137097 650_2 $$2MeSH$$aMethylphenidate: administration & dosage
000137097 650_2 $$2MeSH$$aMethylphenidate: pharmacology
000137097 650_2 $$2MeSH$$aMultimodal Imaging: instrumentation
000137097 650_2 $$2MeSH$$aMultimodal Imaging: methods
000137097 650_2 $$2MeSH$$aPositron-Emission Tomography: instrumentation
000137097 650_2 $$2MeSH$$aPositron-Emission Tomography: methods
000137097 650_2 $$2MeSH$$aPsychiatric Status Rating Scales
000137097 650_2 $$2MeSH$$aRadiopharmaceuticals
000137097 650_2 $$2MeSH$$aYoung Adult
000137097 7001_ $$0P:(DE-HGF)0$$aFryer, Tim D$$b1
000137097 7001_ $$0P:(DE-HGF)0$$aHong, Young T$$b2
000137097 7001_ $$0P:(DE-HGF)0$$aSmith, Rob$$b3
000137097 7001_ $$0P:(DE-HGF)0$$aBrichard, Laurent$$b4
000137097 7001_ $$0P:(DE-2719)2810751$$aAcosta-Cabronero, Julio$$b5$$udzne
000137097 7001_ $$0P:(DE-HGF)0$$aChamberlain, Samuel R$$b6
000137097 7001_ $$0P:(DE-HGF)0$$aTait, Roger$$b7
000137097 7001_ $$0P:(DE-HGF)0$$aIzquierdo, David$$b8
000137097 7001_ $$0P:(DE-HGF)0$$aRegenthal, Ralf$$b9
000137097 7001_ $$0P:(DE-HGF)0$$aDowson, Jonathan$$b10
000137097 7001_ $$0P:(DE-HGF)0$$aSuckling, John$$b11
000137097 7001_ $$0P:(DE-HGF)0$$aBaron, Jean-Claude$$b12
000137097 7001_ $$0P:(DE-HGF)0$$aAigbirhio, Franklin I$$b13
000137097 7001_ $$0P:(DE-HGF)0$$aRobbins, Trevor W$$b14
000137097 7001_ $$0P:(DE-HGF)0$$aSahakian, Barbara J$$b15
000137097 7001_ $$0P:(DE-HGF)0$$aMüller, Ulrich$$b16
000137097 77318 $$2Crossref$$3journal-article$$a10.1093/brain/awt263$$b : Oxford University Press (OUP), 2013-10-25$$n11$$p3252-3270$$tBrain$$v136$$x1460-2156$$y2013
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000137097 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1192/bjp.bp.107.048827$$o10.1192/bjp.bp.107.048827
000137097 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1002/syn.20734$$o10.1002/syn.20734
000137097 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1037/0033-2909.95.3.387$$o10.1037/0033-2909.95.3.387
000137097 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/S0002-7138(09)60604-X$$o10.1016/S0002-7138(09)60604-X
000137097 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/S0166-4328(97)00175-7$$o10.1016/S0166-4328(97)00175-7
000137097 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.biopsych.2006.07.032$$o10.1016/j.biopsych.2006.07.032
000137097 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1111/j.1469-8986.1984.tb00247.x$$o10.1111/j.1469-8986.1984.tb00247.x
000137097 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s00213-005-0025-4$$o10.1007/s00213-005-0025-4
000137097 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s00213-004-1993-5$$o10.1007/s00213-004-1993-5
000137097 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s00213-003-1457-3$$o10.1007/s00213-003-1457-3
000137097 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1006/nimg.2001.0978$$o10.1006/nimg.2001.0978
000137097 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neuroimage.2006.10.013$$o10.1016/j.neuroimage.2006.10.013
000137097 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1176/appi.ajp.163.3.359$$o10.1176/appi.ajp.163.3.359
000137097 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/npp.2012.127$$o10.1038/npp.2012.127
000137097 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1001/jama.2009.1308$$o10.1001/jama.2009.1308
000137097 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neuroimage.2006.10.014$$o10.1016/j.neuroimage.2006.10.014
000137097 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1001/archpsyc.64.8.932$$o10.1001/archpsyc.64.8.932
000137097 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/376572a0$$o10.1038/376572a0