ReviewPathogenesis of depression: Insights from human and rodent studies

- Discoveries related to major depressive disorders (MDD) obtained in rodent models and validated in human depressed subjects.
- Recent findings on neuronal and synaptic remodeling, transcription and epigenetics.
- Functional role of the immune system in the development of depression symptomology.
- Involvement of glial cells in MDD pathogenesis.
- Necessity of novel therapeutic strategies targeting central and peripheral processes.

Major depressive disorder (MDD) will affect one out of every five people in their lifetime and is the leading cause of disability worldwide. Nevertheless, mechanisms associated with the pathogenesis of MDD have yet to be completely understood and current treatments remain ineffective in a large subset of patients. In this review, we summarize the most recent discoveries and insights for which parallel findings have been obtained in human depressed subjects and rodent models of mood disorders in order to examine the potential etiology of depression. These mechanisms range from synaptic plasticity mechanisms to epigenetics and the immune system where there is strong evidence to support a functional role in the development of specific depression symptomology. Ultimately we conclude by discussing how novel therapeutic strategies targeting central and peripheral processes might ultimately aid in the development of effective new treatments for MDD and related stress disorders.

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