RT Journal
A1 Ersche KD, Bullmore ET, Craig KJ, et al
T1 INfluence of compulsivity of drug abuse on dopaminergic modulation of attentional bias in stimulant dependence
JF Archives of General Psychiatry
JO Archives of General Psychiatry
YR 2010
FD June 1
VO 67
IS 6
SP 632
OP 644
DO 10.1001/archgenpsychiatry.2010.60
UL http://dx.doi.org/10.1001/archgenpsychiatry.2010.60
AB Context 
    There are no effective pharmacotherapies for stimulant dependence but there are many plausible targets for development of novel therapeutics. We hypothesized that dopamine-related targets are relevant for treatment of stimulant dependence, and there will likely be individual differences in response to dopaminergic challenges.Objective 
    To measure behavioral and brain functional markers of drug-related attentional bias in stimulant-dependent individuals studied repeatedly after short-term dosing with dopamine D2/D3 receptor antagonist and agonist challenges.Design 
    Randomized, double-blind, placebo-controlled, parallel-groups, crossover design using pharmacological functional magnetic resonance imaging.Setting 
    Clinical research unit (GlaxoSmithKline) and local community in Cambridge, England.Participants 
    Stimulant-dependent individuals (n = 18) and healthy volunteers (n = 18).Interventions 
    Amisulpride (400 mg), pramipexole dihydrochloride (0.5 mg), or placebo were administered in counterbalanced order at each of 3 repeated testing sessions.Main Outcome Measures 
    Attentional bias for stimulant-related words was measured during functional magnetic resonance imaging by a drug-word Stroop paradigm; trait impulsivity and compulsivity of dependence were assessed at baseline by questionnaire.Results 
    Drug users demonstrated significant attentional bias for drug-related words, which was correlated with greater activation of the left prefrontal and right cerebellar cortex. Attentional bias was greater in people with highly compulsive patterns of stimulant abuse; the effects of dopaminergic challenges on attentional interference and related frontocerebellar activation were different between high- and low-compulsivity subgroups.Conclusions 
    Greater attentional bias for and greater prefrontal activation by stimulant-related words constitute a candidate neurocognitive marker for dependence. Individual differences in compulsivity of stimulant dependence had significant effects on attentional bias, its brain functional representation, and its short-term modulation by dopaminergic challenges.