Journal
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
Volume 35, Issue 7, Pages 1623-1630Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pnpbp.2011.06.013
Keywords
Antidepressant; Brain-derived neurotrophic factor (BDNF); Depression; Neurotrophin; SSRI
Funding
- Forest Labs
- NIMH [1 R01 MH083784]
- O'Shaughnessy Foundation
- UCSF Academic Senate
- UCSF Research Evaluation and Allocation Committee (REAC)
- NIH/NCRR UCSF-CTSI [UL1 RR024131]
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Objectives: The neurotrophin hypothesis of depression posits a role of brain-derived neurotrophic factor (BDNF) in depression, although it is unknown whether BDNF is more involved in the etiology of depression or in the mechanism of action of antidepressants. It is also unknown whether pre-treatment serum BDNF levels predict antidepressant response. Methods: Thirty un-medicated depressed subjects were treated with escitalopram (N = 16) or sertraline (N = 14) for 8 weeks. Twenty-five of the depressed subjects completed 8 weeks of antidepressant treatment and had analyzable data. Twenty-eight healthy controls were also studied. Serum for BDNF assay was obtained at baseline in all subjects and after 8 weeks of treatment in the depressed subjects. Depression ratings were obtained at baseline and after 8 weeks of treatment in the depressed subjects. Results: Pre-treatment BDNF levels were lower in the depressed subjects than the controls (p = 0.001) but were not significantly correlated with pre-treatment depression severity. Depression ratings improved with SSRI treatment (p<0.001), and BDNF levels increased with treatment (p = 0.005). Changes in BDNF levels were not significantly correlated with changes in depression ratings. However, pre-treatment BDNF levels were directly correlated with antidepressant responses (p<0.01), and Responders to treatment (>= 50% improvement in depression ratings) had higher pre-treatment BDNF levels than did Non-responders (p<0.05). Conclusions: These results confirm low serum BDNF levels in un-medicated depressed subjects and confirm antidepressant-induced increases in BDNF levels, but they suggest that antidepressants do not work simply by correcting BDNF insufficiency. Rather, these findings are consistent with a permissive or facilitatory role of BDNF in the mechanism of action of antidepressants. (C) 2011 Elsevier Inc. All rights reserved.
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