Mechanism of NMDA receptor-related changes in depression

The aim of the project is to investigate the role of the glutamatergic system in the treatment of depression - to verify the hypothesis that blocking the NMDA receptor with magnesium, zinc or acamprosate will intensify and accelerate the antidepressant effect of fluoxetine. Animal studies and clinical trials increasingly support the role of the NMDA receptor complex in the treatment of depression. Much research has shown that antidepressants (LPDs) can block the NMDA receptor and cause adaptive changes. The concept of the glutamatergic depression theory is also associated with the involvement of brain-derived neurotrophic factor (BDNF). The data contained in the current literature show that during the use of LPD, the level of BDNF in the blood increases. BDNF has been shown to reduce mRNA expression of NMDA receptor subunits. A lot of data also indicate the participation of inflammatory processes in the pathogenesis and treatment of depression. Under the influence of LPD, a decrease in the concentration of pro-inflammatory cytokines, in particular IL-6, was observed. In studies conducted on an animal model at the Institute of Pharmacology of the Polish Academy of Sciences in Krakow, it was shown that magnesium, zinc and acamprosate, by modulating the glutamatergic system, may have antidepressant effects. The data contained in the literature concern tests performed mainly on animals, clinical studies are scarce - they concern attempts to supplement the LPD therapy with zinc and magnesium ions, there are no studies on the potentialisation of LPD with acamprosate. Research method The serum will be collected from patients who have been diagnosed with a depressive episode in the course of recurrent depressive disorders according to ICD-10 or major depression according to DSM-IV. The NMDA receptor blocking effect will be assessed in three study groups: I - fluoxetine + magnesium; II - (Ą O fluoxetine + zinc; 111 - fluoxetine + acamprosate. Control will be fluoxetine + placebo. Serum will be drawn at 6 time points, duration of the study will be 8 weeks. The effect of NMDA receptor blocking will be assessed by a neurophysiological study: -assessment of changes in the pharmacoelectroencephalographic record (method developed at the Department of Psychiatry, Medical University of Warsaw); therapeutic response markers: BDNF and IL-6 levels, fluoxetine, magnesium, zinc and acamprosate levels of mental state: clinical status will be assessed at each time point using scales : Hamilton Depression Scale, Hamilton Scale Anxiety Scale, General Clinical Impression Scale and Adverse Symptoms Scale. The result of the project will be to develop the mechanism of action of NMDA receptor antagonists in the treatment of depression. on animals. It is planned to present the results in the form of a publication, two doctoral theses and a habilitation thesis.