Attention-deficit/hyperactivity disorder (ADHD)--characterized by symptoms of inattention
and hyperactivity-impulsivity--is the most prevalent childhood psychiatric disorder
that frequently persists into adulthood, and there is increasing evidence of reward-motivation
deficits in this disorder.
To evaluate biological bases that might underlie a reward/motivation deficit by imaging
key components of the brain dopamine reward pathway (mesoaccumbens).
We used positron emission tomography to measure dopamine synaptic markers (transporters
and D(2)/D(3) receptors) in 53 nonmedicated adults with ADHD and 44 healthy controls
between 2001-2009 at Brookhaven National Laboratory.
We measured specific binding of positron emission tomographic radioligands for dopamine
transporters (DAT) using [(11)C]cocaine and for D(2)/D(3) receptors using [(11)C]raclopride,
quantified as binding potential (distribution volume ratio -1).
For both ligands, statistical parametric mapping showed that specific binding was
lower in ADHD than in controls (threshold for significance set at P < .005) in regions
of the dopamine reward pathway in the left side of the brain. Region-of-interest analyses
corroborated these findings. The mean (95% confidence interval [CI] of mean difference)
for DAT in the nucleus accumbens for controls was 0.71 vs 0.63 for those with ADHD
(95% CI, 0.03-0.13, P = .004) and in the midbrain for controls was 0.16 vs 0.09 for
those with ADHD (95% CI, 0.03-0.12; P < or = .001); for D(2)/D(3) receptors, the mean
accumbens for controls was 2.85 vs 2.68 for those with ADHD (95% CI, 0.06-0.30, P
= .004); and in the midbrain, it was for controls 0.28 vs 0.18 for those with ADHD
(95% CI, 0.02-0.17, P = .01). The analysis also corroborated differences in the left
caudate: the mean DAT for controls was 0.66 vs 0.53 for those with ADHD (95% CI, 0.04-0.22;
P = .003) and the mean D(2)/D(3) for controls was 2.80 vs 2.47 for those with ADHD
(95% CI, 0.10-0.56; P = .005) and differences in D(2)/D(3) in the hypothalamic region,
with controls having a mean of 0.12 vs 0.05 for those with ADHD (95% CI, 0.02-0.12;
P = .004). Ratings of attention correlated with D(2)/D(3) in the accumbens (r = 0.35;
95% CI, 0.15-0.52; P = .001), midbrain (r = 0.35; 95% CI, 0.14-0.52; P = .001), caudate
(r = 0.32; 95% CI, 0.11-0.50; P = .003), and hypothalamic (r = 0.31; CI, 0.10-0.49;
P = .003) regions and with DAT in the midbrain (r = 0.37; 95% CI, 0.16-0.53; P < or
= .001).
A reduction in dopamine synaptic markers associated with symptoms of inattention was
shown in the dopamine reward pathway of participants with ADHD.