Depressive Episode Clinical Trial
Official title:
Study of the Effect of Antidepressant Drugs on Neurotrophic Factors in Patients With Depression
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.
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