The Role of Brain-Derived Neurotrophic Factor in Mediating the Action of Antidepressants in the Treatment of Depression

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Abstract


According to the neurotrophic hypothesis of depression proposed two decades ago, the most important role in the pathogenesis of depressive disorders is played by abnormalities in the maintenance of neuronal plasticity regulated by brain neurotrophic factor (BDNF). Although the decline in BDNF activity in depression is now widely documented, it remains unclear whether it is a factor contributing to the onset of depression, or a consequence of the chronic course of the disease. In preclinical studies, it was found that exogenous BDNF infusions causes antidepressant-like effects, prevents the depressogenic effects of chronic stress and increases cell survival in the hippocampus and the prefrontal cortex, but the mechanisms mediating these effects have not been fully studied. The results of molecular genetic studies confirmed that BDNF is essential in mediating the therapeutic effect of antidepressants, while the role of genetic polymorphisms in predicting antidepressant efficacy in depression remains uncertain. The mechanisms of action of monoaminergic antidepressants are related to their effect on the expression of BDNF and its TrkB receptor, however, apparently, the effect size varies for different drugs. Peripheral BDNF levels increase during treatment with antidepressants, and this increase is clearly observed only during the acute phase treatment of depression, but not during the period of maintenance therapy. The serum level of BDNF is a potentially useful marker for diagnosing depression and prediction of a therapeutic response.

Tamara I. Vazagaeva

V. Serbsky Federal Medical Research Centre of Psychiatry and Narcology

Author for correspondence.
Email: vazagaeva@mail.ru
ORCID iD: 0000-0002-6018-402X

Russian Federation

MD, PhD.

23, Kropotkinsky pereulok, 119034 Moscow

SPIN-код: 6469-6491

Roman V. Akhapkin

V. Serbsky Federal Medical Research Centre of Psychiatry and Narcology

Email: 4ahapkin@gmail.com
ORCID iD: 0000-0002-7045-0547

MD, PhD

SPIN-код: 9966-0084

Yuri A. Alexandrovsky

V. Serbsky Federal Medical Research Centre of Psychiatry and Narcology

Email: alexandrovsky_u@mail.ru
ORCID iD: 0000-0002-4362-2921

MD, PhD, Professor

SPIN-cod: 9010-2378

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