Depressed Dopamine Activity in Caudate and Preliminary Evidence of Limbic Involvement in Adults With Attention-Deficit/Hyperactivity Disorder

Abstract

Context: Attention-deficit/hyperactivity disorder (ADHD) is the most prevalent psychiatric disorder of childhood. There is considerable evidence that brain dopamine is involved in ADHD, but it is unclear whether dopamine activity is enhanced or depressed.Objective: To test the hypotheses that striatal dopamine activity is depressed in ADHD and that this contributes to symptoms of inattention.Design: Clinical (ADHD adult) and comparison (healthy control) subjects were scanned with positron emission tomography and raclopride labeled with carbon 11 (D 2 /D 3 receptor radioligand sensitive to competition with endogenous dopamine) after placebo and after intravenous methylphenidate hydrochloride (stimulant that increases extracellular dopamine by blocking dopamine transporters). The difference in [11 C]raclopride's specific binding between placebo and methylphenidate was used as marker of dopamine release. Symptoms were quantified using the Conners Adult ADHD Rating Scales.Setting: Outpatient setting.Participants: Nineteen adults with ADHD who had never received medication and 24 healthy controls.Results: With the placebo, D 2 /D 3 receptor availability in left caudate was lower (PϽ.05) in subjects with ADHD than in controls. Methylphenidate induced smaller decrements in [11 C]raclopride binding in left and right caudate (blunted DA increases) (P Ͻ .05) and higher scores on self-reports of "drug liking" in ADHD than in control subjects. The blunted response to methylphenidate in caudate was associated with symptoms of inattention (P Ͻ .05) and with higher self-reports of drug liking (PϽ.01). Exploratory analysis using statistical parametric mapping revealed that methylphenidate also decreased [11 C]raclopride binding in hippocampus and amygdala and that these decrements were smaller in subjects with ADHD (PϽ .001).Conclusions: This study reveals depressed dopamine activity in caudate and preliminary evidence in limbic regions in adults with ADHD that was associated with inattention and with enhanced reinforcing responses to intravenous methylphenidate. This suggests that dopamine dysfunction is involved with symptoms of inattention but may also contribute to substance abuse comorbidity in ADHD. Psychiatry. 2007;64(8):932-940 Arch Gen

Clinical correlations of grey matter reductions in the caudate nucleus of adults with attention deficit hyperactivity disorder

“…41 It is not surprising that we found a reduced volume of a portion the caudate, given that studies using diverse functional imaging techniques (e.g., positron emission tomography) have shown a malfunction in the striatum of adults with ADHD. [42][43][44] Considering our findings and the fact that few studies involving adult ADHD patients have been published, there is a need for additional research into the volume of the caudate nucleus in adults with ADHD.…”

Relationship of Ferritin to Symptom Ratings Children with Attention Deficit Hyperactivity Disorder: Effect of Comorbidity

“…It has been found that iron is closely related to dopamine metabolism being a coenzyme of tyrosine hydroxylase, and that D2 and D4 receptor and dopamine transporter densities decrease with decreased brain iron levels [8][9][10]. It can be speculated that iron deficiency may cause further alterations in brain dopaminergic system, which seems to be already impaired in ADHD subjects [20]. It has been proposed that there might be multiple developmental pathways for ADHD that includes different neuropsychological subtypes [21].…”

Will Working Memory Training Generalize to Improve Off-Task Behavior in Children with Attention-Deficit/Hyperactivity Disorder?

“…A recent positron emission tomography report of 13 healthy adults [11] found increased density of cortical dopamine D1 receptor binding in the PFC and parietal cortex associated with WM training. Thus, training may improve behavioral and cognitive impairments of ADHD related to disturbances of the dopamine system [11,45]. These neuroimaging findings suggest that WM training may have the potential for improved generalization by targeting core weaknesses involved in executive functioning in ADHD populations.…”

“…A functional magnetic resonance study of training in ADHD using a broad package of exercises [44], focusing on response inhibition and selective attention rather than WM, found increased frontal, middle temporal, and cerebellar activity after training. Theoretically, improvement in dopamine functioning, which is altered in ADHD and is targeted by the most efficacious ADHD pharmacologic treatments [45], would also enhance the generalization of training effects. A recent positron emission tomography report of 13 healthy adults [11] found increased density of cortical dopamine D1 receptor binding in the PFC and parietal cortex associated with WM training.…”