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 (62)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Psychiatry  • Depression  • Randomized Controlled Trial  • Alert me on articles by topic  Social Bookmarking   What's this?

Altered Response to Dextroamphetamine

Lescia K. Tremblay, BSc; Claudio A. Naranjo, MD; Laura Cardenas, MD; Nathan Herrmann, MD; Usoa E. Busto, PharmD

Arch Gen Psychiatry. 2002;59:409-416.

Background  The state of the brain reward system in major depressive disorder was assessed with dextroamphetamine, which probes the release of dopamine within the mesocorticolimbic system, a major component of the brain reward system, and produces measurable behavioral changes, including rewarding effects (eg, euphoria). We hypothesized that depressed individuals would exhibit an altered response to dextroamphetamine due to an underlying brain reward system dysfunction reflected by anhedonic symptoms.

Methods  In a double-blind, placebo-controlled, randomized, parallel study, the behavioral and physiological effects of a single 30-mg dose of oral dextroamphetamine sulfate were measured. Forty patients with a diagnosis of DSM-IV major depressive disorder who were not taking antidepressant medications (22 assigned to dextroamphetamine and 18 to placebo) were compared with 36 control subjects (18 assigned to dextroamphetamine and 18 to placebo) using validated self-report drug effect measurement tools (eg, the Addiction Research Center Inventory), heart rate, and blood pressure.

Results  Multiple regression analysis showed that severity of depression as measured by the Hamilton Rating Scale for Depression correlated highly with the rewarding effects of dextroamphetamine in the depressed group (model R² = 0.63; interaction P = .04). A subsequent analysis categorizing the depressed group into patients with severe symptoms (Hamilton score >23) and those with moderate symptoms revealed a significant interaction between drug and depression (P = .02). Patients with severe symptoms reported rewarding effects 3.4-fold greater than controls.

Conclusions  The results suggest the presence of a hypersensitive response is present in the brain reward system of depressed patients, which may reflect a hypofunctional state and may provide a novel pathophysiologic and therapeutic target for future studies.

From the Psychopharmacology Research Program, Sunnybrook & Women's College Health Sciences Centre–Sunnybrook Campus (Ms Tremblay and Drs Naranjo, Herrmann, and Busto), the Centre for Addiction and Mental Health, Addiction Research Centre Site (Drs Cardenas and Busto), and the Departments of Pharmacology (Drs Cardenas, Herrmann, and Busto), Psychiatry (Drs Naranjo and Herrmann), Medicine (Drs Naranjo and Herrmann), and Pharmaceutical Sciences (Ms Tremblay and Dr Busto), University of Toronto, Toronto, Ontario.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Major Depressive Disorder
Belmaker and Agam
NEJM 2008;358:55-68.
FULL TEXT  

Neural Evidence for Enhanced Error Detection in Major Depressive Disorder
Chiu and Deldin
Am. J. Psychiatry 2007;164:608-616.
ABSTRACT | FULL TEXT  

The Role of Dopamine in the Pathophysiology of Depression
Dunlop and Nemeroff
Arch Gen Psychiatry 2007;64:327-337.
FULL TEXT  

Co-Occurring Mental and Substance Use Disorders: The Neurobiological Effects of Chronic Stress
Brady and Sinha
Focus 2007;5:229-239.
ABSTRACT | FULL TEXT  

Functional Neuroanatomical Substrates of Altered Reward Processing in Major Depressive Disorder Revealed by a Dopaminergic Probe
Tremblay et al.
Arch Gen Psychiatry 2005;62:1228-1236.
ABSTRACT | FULL TEXT  

Co-Occurring Mental and Substance Use Disorders: The Neurobiological Effects of Chronic Stress
Brady and Sinha
Am. J. Psychiatry 2005;162:1483-1493.
ABSTRACT | FULL TEXT  

Taste responses in patients with Parkinson's disease
Sienkiewicz-Jarosz et al.
J. Neurol. Neurosurg. Psychiatry 2005;76:40-46.
ABSTRACT | FULL TEXT  

Characteristics of Depressed Preschoolers With and Without Anhedonia: Evidence for a Melancholic Depressive Subtype in Young Children
Luby et al.
Am. J. Psychiatry 2004;161:1998-2004.
ABSTRACT | FULL TEXT  

Psychobiological Mechanisms of Resilience and Vulnerability: Implications for Successful Adaptation to Extreme Stress
Charney
Focus 2004;2:368-391.
ABSTRACT | FULL TEXT  

S32504, a Novel Naphtoxazine Agonist at Dopamine D3/D2 Receptors: III. Actions in Models of Potential Antidepressive and Anxiolytic Activity in Comparison with Ropinirole
Millan et al.
J. Pharmacol. Exp. Ther. 2004;309:936-950.
ABSTRACT | FULL TEXT  

Psychobiological Mechanisms of Resilience and Vulnerability: Implications for Successful Adaptation to Extreme Stress
Charney
Am. J. Psychiatry 2004;161:195-216.
ABSTRACT | FULL TEXT  

Brain Reward System Activity in Major Depression and Comorbid Nicotine Dependence
Cardenas et al.
J. Pharmacol. Exp. Ther. 2002;302:1265-1271.
ABSTRACT | FULL TEXT  

A Dimensional Approach to the Neurobiology of Depression
JWatch Psychiatry 2002;2002:4-4.
FULL TEXT