The aim of the present study will be to observe the changes in the NTs like Nerve growth factor, Neurotrophin-3, and Neurotrophin-4 in patients with depression and study the effect of various antidepressants like Sertraline (SSRI), Dosulepin (TCA), and Venlafaxine (SNRI) on their levels.
Depression is one of the common psychiatric disorders, with a worldwide prevalence of around 16·2%, with multifactorial causality, but partially unknown pathophysiology. Depression likely involves, at a molecular and cellular level, dysfunctions of critical neurotrophic, cellular plasticity and resilience pathways and neuroprotective processes. In context to Neurotropic hypothesis, in depression there is reduction in Neurotrophins (NTs), which impairs the pruning of the neural network, alters neural plasticity, and impacts negatively on the structural and functional processes within the limbic system. NTs in general and Brain Derived Neurotrophic Factor (BDNF) in particular modulate depressive behavior and the response to antidepressant treatment, in part through the regulation of synaptic plasticity, synaptogenesis, and neurogenesis. Major neurotrophins like nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) have been identified in context to nervous system functioning. Previous studies have consistently proved the reduction in BDNF levels in patients with depression and antidepressants were found to increase BDNF protein levels with re-establishment of normative cortical networks in different areas of hippocampus. Recent studies have provided important links between the neurobiological characteristics of depression and NGF. Animal studies have revealed decreasing levels of NGF in specific brain areas of different mouse models, including anxiety vulnerability, stress-induced illness, and learned helplessness. In relation to the patients with depression, NGF has been recognized as an important factor in modulating their altered or dysfunctional hypothalamic-pituitary-adrenal (HPA) axis. Previous studies have compared the differences in peripheral NGF levels in patients with depression and healthy controls, others have investigated the effect of different treatments on their levels. The results have been conflicting in relation to NGF levels results before and after antidepressant treatment in patients with depression, thus, necessitating the need for further research in this area. Studies related to NT-3 levels in unipolar depression is limited, when researchers have reported of increased CSF levels of NT-3 in elderly depressed patients and increased serum NT-3 levels in the depressive phase of Bipolar disorder. Lower level of neurotrophins like BDNF, but higher level of NT-3, have been found in depressed patients with schizophrenia. NT-4 has been a potential candidate neurotropic factor for research in patients with mood disorder. Studies have reported of increased serum NT-4 levels in the depressive phase of Bipolar disorder, when others have found the increase in serum NT-4 levels in both the depressive and manic phases of the illness. Contrastingly, studies have also found reduction in NT-4 levels in the manic phase of Bipolar disorder. The literature search clearly reveals the lack of studies or inconsistent findings in relation to the role of major NTs like NGF, Neurotrophin-3, and Neurotrophin-4 in unipolar depression. It will be worth studying the changes in these NTs in depression and the effect of various antidepressants on their levels, this can help us in understanding the caveats in pathophysiology of depression better, which can have future treatment implications. The aim of the present study will be to observe the changes in the NTs like Nerve growth factor, Neurotrophin-3, and Neurotrophin-4 in patients with depression and study the effect of various antidepressants like Sertraline (SSRI), Dosulepin (TCA), and Venlafaxine (SNRI) on their levels.
Study Type
OBSERVATIONAL
Enrollment
105
Tab. Sertraline 50 mg/day, which will be optimized to 75mg/day after 2 weeks if required, and maintained on the same dose for a minimum period of 6 weeks.
Tab. Dosulepin 25mg/day, which will be gradually hiked up to 75mg/day over 2 weeks,and the patients will be continued on the same dose for a minimum period of 6 weeks.
Tab. Venlafaxine 75mg/day, which will be hiked to 112.5 mg/day after 2 weeks, and the patients will be continued on the same dose for a minimum period of 6 weeks.
Dept of Psychiatry, Aiims, Bhubaneswar
Bhubaneswar, Odisha, India
Change in serum nerve growth factor from baseline over 6 weeks
ELISA
Time frame: Baseline and 6 weeks
Change in serum neurotrophin 3 from baseline over 6 weeks
ELISA
Time frame: Baseline and 6 weeks
Change in serum neurotrophin 4 from baseline over 6 weeks
ELISA
Time frame: Baseline and 6 weeks
Change in severity of symptoms of depression from baseline over 6 weeks
Montgomery-Åsberg Depression Rating Scale
Time frame: Baseline and 6 weeks
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