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- Title
Regional Brain Metabolic Correlates of α-Methylparatyrosine–Induced Depressive Symptoms: Implications for the Neural Circuitry of Depression.
- Authors
Bremner, J. Douglas; Vythilingam, Meena; Ng, Chin K.; Vermetten, Eric; Nazeer, Ahsan; Oren, Dan A.; Berman, Robert M.; Charney, Dennis S.
- Abstract
Context: We previously used positron emission tomography (PET) measurement of brain metabolism with fluorodeoxyglucose to show that patients receiving selective serotonin reuptake inhibitors (SSRIs) who have a tryptophan depletion–induced return of depressive symptoms have an acute decrease in metabolism in orbitofrontal cortex, dorsolateral prefrontal cortex, and thalamus. Many patients with depression in remission while taking norepinephrine reuptake inhibitors (NRIs) (but not SSRIs) experience a return of depressive symptoms with depletion of norepinephrine and dopamine using α-methylparatyrosine (AMPT). Objective: To assess brain metabolic correlates of AMPT administration in patients with depression in remission while receiving NRIs. Design, Setting, and Participants: Randomized, controlled, double-blind trial in which 18 patients recruited in 1997-2000 from the general community who had depression in remission while taking NRIs had PET imaging in a psychiatric research unit following AMPT and placebo administration. Interventions: After initial medication with desipramine and follow-up until response, patients underwent active AMPT (five 1-g doses administered orally over 28 hours) and placebo (diphenhydramine hydrochloride, five 50- mg doses administered similarly) catecholamine depletion challenges in randomized order of assignment, after which PET imaging was performed on day 3 of each condition. Both study conditions were performed 1 week apart. Main Outcome Measures: Regional brain metabolism rates in patients with and without AMPT-induced return of depressive symptoms. Results: AMPT-induced return of depressive symptoms was experienced by 11 of the 18 patients and led to decreased brain metabolism in a number of cortical areas, with the greatest magnitude of effects in orbitofrontal (P = .002) and dorsolateral prefrontal (P = .03) cortex and thalamus (P = .006). Increased resting metabolism in prefrontal and limbic areas...
- Subjects
POSITRON emission tomography; SEROTONIN uptake inhibitors; MENTAL depression; BRAIN; FRONTAL lobe
- Publication
JAMA: Journal of the American Medical Association, 2003, Vol 289, Issue 23, p3125
- ISSN
0098-7484
- Publication type
Article
- DOI
10.1001/jama.289.23.3125