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Updated: Apr 11, 2026
Animal Models of Depression - Chronic Despair Model CDM
Published on: September 23, 2021
Pathogenesis of depression: Insights from human and rodent studies
C Ménard1, G E Hodes1, S J Russo1
1Fishberg Department of Neuroscience and the Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Abstract:
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.
Insights
This review explores the biological underpinnings of major depressive disorder (MDD), examining shared findings in human patients and animal models to uncover potential causes and inform new treatments.
Area of Science:
- Neuroscience
- Psychiatry
- Genetics
Background:
- Major depressive disorder (MDD) is a global health issue, affecting 20% of individuals and causing significant disability.
- The precise mechanisms driving MDD pathogenesis remain unclear, limiting the effectiveness of current therapies for many patients.
Purpose of the Study:
- To review recent discoveries on the etiology of depression by comparing findings in human subjects with mood disorders and rodent models.
- To identify biological mechanisms, including synaptic plasticity, epigenetics, and immune system involvement, implicated in depression.
Main Methods:
- Comparative analysis of human clinical data and preclinical rodent models of mood disorders.
- Synthesis of recent research on synaptic plasticity, epigenetic modifications, and immune system function in relation to depression.
Main Results:
- Evidence suggests a functional role for synaptic plasticity, epigenetics, and the immune system in the development of specific depressive symptoms.
- Parallel findings in human and animal studies highlight conserved biological pathways relevant to MDD.
Conclusions:
- Understanding these complex mechanisms is crucial for developing novel therapeutic strategies for MDD.
- Targeting both central and peripheral processes offers a promising avenue for creating more effective treatments for depression and stress-related disorders.
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