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Probing brain reward system function in major depressive disorder: altered response to dextroamphetamine
Lescia K Tremblay1, Claudio A Naranjo, Laura Cardenas
1Psychopharmacology Research Program, Sunnybrook & Women's College Health Sciences Centre-Sunnybook Campus, University of Toronto, 2075 Bayview Ave, Room F-327, Toronto, Ontario, Canada M4N 3M5.
Archives of General Psychiatry
|May 2, 2002
Summary
Major depressive disorder patients show a hypersensitive brain reward system response to dextroamphetamine, suggesting dysfunction. This finding may offer new therapeutic targets for depression treatment.
Area of Science:
- Neuroscience
- Psychiatry
- Pharmacology
Background:
- Major depressive disorder (MDD) is associated with dysfunction in the brain's reward system.
- Dopamine release in the mesocorticolimbic system is a key indicator of reward system function.
- Anhedonia, a common symptom of depression, suggests impaired reward processing.
Purpose of the Study:
- To assess the brain reward system's state in MDD using dextroamphetamine.
- To investigate the relationship between depression severity and dextroamphetamine's effects.
- To determine if MDD patients exhibit altered behavioral and physiological responses to dextroamphetamine.
Main Methods:
- A double-blind, placebo-controlled, randomized study.
- 30-mg oral dextroamphetamine sulfate dose administered to 40 MDD patients and 36 controls.
- Behavioral effects measured using self-report tools; physiological effects monitored via heart rate and blood pressure.
Main Results:
- Depression severity strongly correlated with dextroamphetamine's rewarding effects in MDD patients (R(2) = 0.63).
- Patients with severe MDD (Hamilton score >23) reported 3.4-fold greater rewarding effects compared to controls.
- A significant interaction between dextroamphetamine and depression severity was observed (P =.02).
Conclusions:
- Depressed patients exhibit a hypersensitive brain reward system response to dextroamphetamine.
- This hypersensitivity may indicate an underlying hypofunctional reward system in MDD.
- The findings suggest potential novel pathophysiologic mechanisms and therapeutic targets for depression.