A longitudinal study of stress-induced hippocampal volume changes in mice that are susceptible or resilient to chronic social defeat

Hippocampus. 2014 Sep;24(9):1120-8. doi: 10.1002/hipo.22296. Epub 2014 May 7.


Hippocampal shrinkage is a commonly found neuroanatomical change in stress-related mood disorders such as depression and post-traumatic stress disorders (PTSD). Since the onset and severity of these disorders have been found to be closely related to stressful life events, and as stress alone has been shown to reduce hippocampal volume in animal studies, vulnerability to mood disorders may be related to a susceptibility to stress-induced hippocampal shrinkage. However, a smaller hippocampal volume before stress exposure has also been suggested to confer vulnerability of stressed individuals to PTSD or depression. In this study, we examined the contribution of either innate hippocampal volume differences or hippocampal susceptibility to stress-induced shrinkage to the formation of stress-related psychopathology using longitudinal MRI measurements of hippocampal volume in inbred C57 mice before and after chronic social defeat stress. We found that only half of the stressed C57 mice were susceptible to stress and developed psychopathological behaviors such as social avoidance. The other half was resilient to stress and exhibited no social avoidance. Before exposure to stress, we observed a positive correlation between hippocampal volume and social avoidance. After chronic social defeat stress, we found significant increases in left hippocampal volume in resilient and nonstressed control mice. Intriguingly, this increase in hippocampal volume was not found in susceptible mice, suggesting an arrestment of hippocampal growth in these mice. Our findings suggest that both a susceptibility to stress-induced hippocampal volume changes and a larger hippocampus before stress exposure confer vulnerability to psychopathology after chronic stress.

Keywords: chronic stress; individual differences; neuroimaging; resilience; social behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avoidance Learning
  • Body Weight
  • Chronic Disease
  • Disease Models, Animal
  • Dominance-Subordination
  • Functional Laterality
  • Hippocampus / pathology*
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Mice, Inbred C57BL
  • Organ Size
  • Resilience, Psychological*
  • Social Behavior
  • Stress, Psychological / pathology*
  • Stress, Psychological / psychology