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Chapter 4
Abstract
Attention-deficit/hyperactivity disorder (ADHD) is accompanied by impairments in
cognitive control, such as task-switching deficits. We investigated whether such problems,
and their remediation by medication, reflect abnormal reward motivation and associated
striatal dopamine transmission in ADHD. We employed functional genetic neuroimaging
to assess effects of dopaminergic medication and reward motivation on task switching and
striatal BOLD signal in 23 adults with ADHD ON and OFF methylphenidate and 26 healthy
controls. Critically, we took into account inter-individual variability in striatal dopamine
by exploiting a common genetic polymorphism (3’-UTR VNTR) in the DAT1 gene coding
for the dopamine transporter. Results revealed a highly significant group by genotype
interaction in the striatum. This was due to a subgroup of patients with ADHD exhibiting
greatly exaggerated effects of reward on striatal BOLD signal during task switching when
they were OFF their dopaminergic medication. Specifically, patients carrying the 9R allele
showed greater striatal signal than healthy controls carrying this allele, while no effect of
diagnosis was observed in 10R homozygotes. Aberrant striatal responses were normalized
when 9R-carrying patients with ADHD were ON medication. These pilot data demonstrate
an important role for aberrant reward motivation, striatal dopamine and inter-individual
genetic differences in cognitive processes in adult ADHD.