Pathogenesis of depression: Insights from human and rodent studies

Neuroscience. 2016 May 3:321:138-162. doi: 10.1016/j.neuroscience.2015.05.053. Epub 2015 May 30.


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.

Keywords: astrocytes; cytokines; epigenetics; immune system; major depressive disorder; synaptic plasticity.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Behavior, Animal
  • Brain / pathology
  • Brain / physiopathology
  • Depression / immunology
  • Depression / pathology
  • Depression / physiopathology
  • Depression / psychology
  • Depressive Disorder, Major / immunology
  • Depressive Disorder, Major / pathology
  • Depressive Disorder, Major / physiopathology
  • Depressive Disorder, Major / psychology*
  • Disease Models, Animal*
  • Humans
  • Mice
  • Microglia / immunology
  • Microglia / physiology
  • Neuronal Plasticity
  • Neurons / pathology
  • Neurons / physiology
  • Rats
  • Synapses / pathology
  • Synapses / physiology