Direct and indirect evidences of BDNF and NGF as key modulators in depression: role of antidepressants treatment

PURPOSE: Depression is one of the most prevalent, recurrent and life-threatening mental illnesses. However, the precise mechanism underlying the disorder is not yet clearly understood. It is therefore, essential to identify the novel biomarkers which may help in the development of effective treatment. METHODS: In this milieu, the profile of the brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were considered as biomarkers in the light of pathophysiology of depression and its treatment. RESULTS: Previously, we have reported that BDNF level in the postmortem brain of suicide victims was significantly lower than those of normal controls. We also found decreased BDNF levels in the specific brain regions of the learned helplessness model of depression in rat, and was found to increase normal level following chronic fluoxetine hydrochloride treatment. NGF is another important member of neurotrophin, which is dysregulated in the pathophysiology of depression in some models of peripheral nerve damage and stress. The results shown evidences of the effect of antidepressants on modulating depression via the NGF in preclinical and clinical models of depression, but conflicted, therefore make it currently difficult to affirm the therapeutic role of antidepressants. CONCLUSIONS: Here, we review some of the preclinical and clinical studies aimed at disclosing the role of BDNF and NGF mediated pathophysiological mechanisms of depression and the new therapeutic approaches targeting those key molecules. In addition, an important link between BDNF, NGF and depression has been discussed in the light of current existing knowledge.