Abstract

Based on WHO 2021, depressive disorders in adults have an incidence rate of 5% globally, where women experience them more than men, and these severe depressive disorders can lead to suicide. This value is about to increase each year and can also increase due to a certain global health condition like the COVID-19 pandemic. Depressive disorder is a complex mental disorder that involves some mechanisms of neural synaptic dysfunction, chemical imbalance, and brain plasticity. All these changes occur either at the cellular or molecular level and involve all neurotransmitters, ions, neural signaling pathways, neurotrophic factors such as BDNF, as well as the human immune system. It can be classified as a neurodegenerative disease since changes morphologically occur; some of them are in the size, volume, and shape of several brain regions and the disruption processes of their synaptic mechanisms, but only small changes occur in the number of neurons (based on a post mortem brain study). BDNF has dual roles in depression; it is one of the essential neurotropic factors involved in the disease progression and the response to antidepressant treatments that can result in decreased efficacy, while in the depression condition, the level of BDNF is commonly very low, although BDNF is not a biomarker of the disorder or severity. Not all antidepressant drugs successfully influence the level of BDNF, and some antidepressants can affect the level of BDNF after some weeks of treatment, even more than two months, and up to six months of treatment. Here, I would like to describe the specific mechanism of certain subunits of GABAA receptors on the level of BDNF and the related underlie mechanisms of depression, such as the alteration of neurotransmitter levels in certain brain regions, ions, and the fastest signaling pathways (compared to conventional antidepressant agents), as a new direction of major depression treatment.