Depressed Dopamine Activity in Caudate and Preliminary Evidence of Limbic Involvement in Adults With Attention-Deficit/Hyperactivity Disorder | Attention Deficit/Hyperactivity Disorders | JAMA Psychiatry | JAMA Network
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Original Article
August 2007

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

Author Affiliations

Author Affiliations: National Institute on Drug Abuse, Bethesda, Maryland (Dr Volkow); Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, Bethesda (Drs Volkow, Telang, and Ma); Medical and Chemistry Departments, Brookhaven National Laboratory, Upton, New York (Drs Wang, Fowler, and Logan and Mr Wong); Department of Psychiatry, Mount Sinai Medical Center, New York, New York (Drs Newcorn, Solanto, and Schulz); Department of Applied Mathematics, State University of New York at Stony Brook (Mr Pradhan); and Child Development Center, University of California, Irvine (Dr Swanson).

Arch Gen Psychiatry. 2007;64(8):932-940. doi:10.1001/archpsyc.64.8.932
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 (D2/D3 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 [11C]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, D2/D3 receptor availability in left caudate was lower (P < .05) in subjects with ADHD than in controls. Methylphenidate induced smaller decrements in [11C]raclopride binding in left and right caudate (blunted DA increases) (P < .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 < .05) and with higher self-reports of drug liking (P < .01). Exploratory analysis using statistical parametric mapping revealed that methylphenidate also decreased [11C]raclopride binding in hippocampus and amygdala and that these decrements were smaller in subjects with ADHD (P < .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.

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