Past Issues

Targeting Brain-derived Neurotrophic Factor (BDNF) Signaling Pathway as a Treatment Strategy for Depression

Shih-Jen Tsai, M.D.

Major depressive disorder (MDD) is a common mental disorder accounting for signifi cant morbidity and an increase in mortality worldwide. Antidepressants are often recommended as fi rst-line treatment options in MDD patients. But the clinical management of depression with antidepressants remains a major concern for psychiatrists, and there is a need for more effective and quick onset antidepressants beyond the monoaminergic modulation. Studies in recent two decades have provided strong evidence for the neurotrophic hypothesis of MDD, suggesting that stress and antidepressant treatments exert opposing infl uences on the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. BDNF-mediated changes in adult hippocampal neurogenesis is critical for the therapeutic actions of antidepressant treatments. Therefore, up-regulation of BDNF signaling represents an intriguing opportunity to enhance response rates, and to have faster therapeutic onset in MDD. Those drugs that have received preclinical testing include agents that increase BDNF levels (cysteamine, deltamethrin, zinc, hydrogen sulfi de, magnesium, S 47445, TC G-1008, sodium butyrate, inosine, curcumin, riluzole, and harmine), agents that activate BDNF receptors (7,8-dihydroxyfl avone, and isofl urane), and agents that increase BDNF/proBDNF ratio (atorvastatin, and zileuton). The neurotrophic hypothesis of MDD may provide opportunity to develop faster and more effi cient antidepressant drugs with higher response rates.
Key Word major depressive disorders, antidepressants, brain-derived neurotrophic factor (BDNF), tyrosine kinase B
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