• Online Features  This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (73)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Psychiatry  • Attention Deficit Hyperactivity Disorder  • Alert me on articles by topic  Social Bookmarking   What's this?

Nora D. Volkow, MD; Gene-Jack Wang, MD; Jeffrey Newcorn, MD; Frank Telang, MD; Mary V. Solanto, PhD; Joanna S. Fowler, PhD; Jean Logan, PhD; Yeming Ma, PhD; Kurt Schulz, PhD; Kith Pradhan, MS; Christopher Wong, MS; James M. Swanson, PhD

Arch Gen Psychiatry. 2007;64(8):932-940.

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.

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).

CiteULike    Connotea    Delicious    Digg    Facebook    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Methylphenidate-Elicited Dopamine Increases in Ventral Striatum Are Associated with Long-Term Symptom Improvement in Adults with Attention Deficit Hyperactivity Disorder
Volkow et al.
J. Neurosci. 2012;32:841-849.
ABSTRACT | FULL TEXT  

Role for the Membrane Receptor Guanylyl Cyclase-C in Attention Deficiency and Hyperactive Behavior
Gong et al.
Science 2011;333:1642-1646.
ABSTRACT | FULL TEXT  

Parcellating the neuroanatomical basis of impaired decision-making in traumatic brain injury
Newcombe et al.
Brain 2011;134:759-768.
ABSTRACT | FULL TEXT  

Gender-specific expression of the DRD4 gene on adolescent delinquency, anger and thrill seeking
Dmitrieva et al.
Soc Cogn Affect Neurosci 2011;6:82-89.
ABSTRACT | FULL TEXT  

Comorbidity of ADHD and Substance Use Disorder (SUD): A Neuroimaging Perspective
Frodl
J Atten Disord 2010;14:109-120.
ABSTRACT  

Stimulant Medication and Prefrontal Functional Connectivity During Working Memory in ADHD: A Preliminary Report
Sheridan et al.
J Atten Disord 2010;14:69-78.
ABSTRACT  

Dysregulation of Dopamine Transporters via Dopamine D2 Autoreceptors Triggers Anomalous Dopamine Efflux Associated with Attention-Deficit Hyperactivity Disorder
Bowton et al.
J. Neurosci. 2010;30:6048-6057.
ABSTRACT | FULL TEXT  

Emotional deficits in adult ADHD patients: an ERP study
Herrmann et al.
Soc Cogn Affect Neurosci 2009;4:340-345.
ABSTRACT | FULL TEXT  

Evaluating Dopamine Reward Pathway in ADHD: Clinical Implications
Volkow et al.
JAMA 2009;302:1084-1091.
ABSTRACT | FULL TEXT  

Mesolimbic Functional Magnetic Resonance Imaging Activations during Reward Anticipation Correlate with Reward-Related Ventral Striatal Dopamine Release
Schott et al.
J. Neurosci. 2008;28:14311-14319.
ABSTRACT | FULL TEXT  

Methylphenidate-Induced Increases in Vesicular Dopamine Sequestration and Dopamine Release in the Striatum: The Role of Muscarinic and Dopamine D2 Receptors
Volz et al.
J. Pharmacol. Exp. Ther. 2008;327:161-167.
ABSTRACT | FULL TEXT