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How antidepressant drugs act: A primer on neuroplasticity as the eventual mediator of antidepressant efficacy

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Author(s): Andrade Chittaranjan | Rao N

Journal: Indian Journal of Psychiatry
ISSN 0019-5545

Volume: 52;
Issue: 4;
Start page: 378;
Date: 2010;
Original page

Keywords: Depression | stress | antidepressant drugs | electroconvulsive therapy | hippocampus | amygdala | prefrontal cortex | neuroplasticity | mechanism of action

ABSTRACT
Depression is conventionally viewed as a state of chemical imbalance, and antidepressants are suggested to act through increasing monoaminergic neurotransmission. These views are currently considered simplistic. This article examines the animal and human literature on the neurohistological mechanisms underlying stress, depression and antidepressant treatment. Pathological stress and depression are associated with changes such as loss of dendritic spines, shrinkage of the dendritic tree and loss of synapses in the hippocampus and prefrontal cortex. There is also a decrease in glia. Apoptosis may occur under extreme circumstances. In contrast, there is increased dendritic arborization and synaptogenesis in the amygdala. Antidepressant treatment protects against and even reverses some but not all of these stress-induced neurohistological changes. Pathological stress results in an aberrant neuroplasticity response characterized by abnormally increased activity in the amygdala and by impaired functioning of the hippocampus, prefrontal cortex and downstream structures. This aberrant neuroplasticity response directly explains most of the clinical symptoms of depression. Antidepressant treatment protects against stress-induced pathoplastic neurohistological and neurocognitive changes. Antidepressant treatment also restores functional neuroplasticity in stressed organisms and, thereby, presumably, facilitates re-adaptation through learning and memory mechanisms. Thus, the stress-depression syndrome and the therapeutic and prophylactic efficacy of antidepressant treatments can be explained through a hardwiring analogy. In this context, glutamate is an important neurotransmitter.
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