Striatal sensitivity during reward processing in attention-deficit/hyperactivity disorder.
OBJECTIVE
Attention-deficit/hyperactivity disorder (ADHD) has been linked to deficits in the dopaminergic reward-processing circuitry; yet, existing evidence is limited, and the influence of genetic variation affecting dopamine signaling remains unknown. We investigated striatal responsivity to rewards in ADHD combined type (ADHD-CT) using functional magnetic resonance imaging (fMRI), and whether it is modulated by variation in the dopamine transporter gene (DAT1).


METHODS
We tested 29 male adolescents with ADHD-CT and 30 age-, handedness-, and gender-matched healthy controls who were selected for DAT1(10/6) haplotype dosage. Based on previous research, we focused our analysis on the ventral striatum and the caudate nucleus.


RESULTS
Three main findings emerged. First, male adolescents with ADHD-CT did not differ from controls in terms of blood oxygen-level dependent (BOLD) fMRI response to reward-predicting cues (gain or loss-avoidance) in the ventral striatum. Second, male adolescents with ADHD-CT showed a relative increase, compared with controls, in the striatal BOLD response to successful outcomes. Third, DAT1(10/6) dosage differentially modulated neural activation to reward-predicting cues in the caudate nucleus in the ADHD-CT and control groups.


CONCLUSIONS
The findings challenge the idea of a deficit in anticipation-related activation in the ventral striatum in male adolescents with ADHD-CT, while suggesting that the processing of reward outcomes is dysfunctional, consistent with a recent neurobiological model of the disorder. Preliminary evidence suggests that polymorphic variations in genes affecting dopamine signaling need to be taken into consideration when investigating reward-related deficits in ADHD-CT.
King's College London, Medical Research Council Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, UK. Yannis.Paloyelis@kcl.ac.uk
Yannis
Y
Paloyelis
Mitul A
MA
Mehta
Stephen V
SV
Faraone
Philip
P
Asherson
Jonna
J
Kuntsi
D000293:Adolescent; D059031:Anticipation, Psychological / Q000502:physiology; D001143:Arousal / Q000502:physiology; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology; D001479:Basal Ganglia / Q000503:physiopathology*; D001931:Brain Mapping; D002421:Caudate Nucleus / Q000503:physiopathology; D003463:Cues; D003657:Decision Making / Q000502:physiology; D004292:Dominance, Cerebral / Q000502:physiology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics; D056344:Executive Function / Q000502:physiology; D030141:Feedback, Psychological / Q000502:physiology; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009042:Motivation / Q000502:physiology*; D009415:Nerve Net / Q000503:physiopathology; D010100:Oxygen / Q000097:blood; D012016:Reference Values; D012201:Reward
D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; D010100:Oxygen