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Cited by 229Neurotransmitter Receptor Influence on BehaviorTreatment of Major DepressionNeural and Behavioral Psychology Studies

Probing Brain Reward System Function in Major Depressive Disorder: Altered Response to Dextroamphetamine

Tremblay, Lescia K., Naranjo, Claudio A., Cardenas, Laura, Herrmann, Nathan, Busto, Usoa E.·2002·Archives of General Psychiatry
DOI 10.1001/archpsyc.59.5.409
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Abstract

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 R(2) = 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.

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  • The severity of MDD correlates strongly with the magnitude of the rewarding effects of oral D-amphetamine, and anhedonic symptoms in the general population predict rewarded effort-based decision-making.

    “Additionally, the severity of MDD has been found to correlate strongly with the magnitude of the rewarding effects of administration of oral D-amphetamine, which increases DA availability [208], and anhedonic symptoms in the general population predict rewarded effort-based decision-making [209].”

    From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [208]

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Authors
Tremblay, L. K., Naranjo, C. A., Cardenas, L., Herrmann, N., & Busto, U. E.
Affiliations
Sunnybrook Health Science Centre (CA)
Corresponding author
Naranjo, Claudio A.
ORCID
Herrmann, Nathan
Venue
Archives of General Psychiatry
Publisher
American Medical Association (AMA)
Published
2002-05-01
Volume
59
Issue
5
Pages
409
ISSN
0003-990X (ISSN-L)
DOI
10.1001/archpsyc.59.5.409
OpenAlex
W2116248687
Cited by
229
References
81
Citations by year
2025: 3 · 2024: 3 · 2022: 1 · 2021: 5 · 2020: 44 · 2019: 5 · 2018: 9 · 2017: 3 · 2016: 2 · 2015: 6 · 2014: 14 · 2013: 10 · 2012: 14
FWCI
4.42
Type
journal article
Language
en
Open access
closed
Locations
  • Archives of General Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords
major depressive disorder, brain reward system, d-amphetamine, mesocorticolimbic dopamine system, anhedonia, rewarding effects, depression severity, heart rate, blood pressure
MeSH terms
Adult, Blood Pressure, Brain, Depressive Disorder, Dextroamphetamine, Dopamine, Double-Blind Method, Emotions, Euphoria, Female, Heart Rate, Humans, Limbic System, Male, Middle Aged, Neural Pathways, Personality Inventory, Placebos, Psychiatric Status Rating Scales, Regression Analysis, Reward, Severity of Illness Index

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