Tse Yiu Chung, Montoya Ixchel, Wong Alice S, Mathieu Axel, Lissemore Jennifer, Lagace Diane C, Wong Tak Pan
Douglas Mental Health University Institute, McGill University, 6875 LaSalle Boulevard, Montreal, Quebec, Canada.
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.
海马体萎缩是在与压力相关的情绪障碍（如抑郁症和创伤后应激障碍（PTSD））中常见的神经解剖学变化。由于已发现这些障碍的发作和严重程度与应激性生活事件密切相关，并且在动物研究中已表明仅压力就会减少海马体体积，因此对情绪障碍的易感性可能与对应激诱导的海马体萎缩的易感性有关。然而，也有人提出在压力暴露之前较小的海马体体积会使受压力个体易患PTSD或抑郁症。在本研究中，我们使用近交C57小鼠在慢性社会挫败应激前后海马体体积的纵向MRI测量，研究了先天海马体体积差异或海马体对应激诱导萎缩的易感性对压力相关精神病理学形成的作用。我们发现，只有一半受压力的C57小鼠对应激敏感并出现社会回避等精神病理行为。另一半对应激具有弹性，没有表现出社会回避。在暴露于压力之前，我们观察到海马体体积与社会回避之间呈正相关。在慢性社会挫败应激后，我们发现有弹性和无压力的对照小鼠左海马体体积显著增加。有趣的是，在易感小鼠中未发现海马体体积的这种增加，这表明这些小鼠的海马体生长停滞。我们的研究结果表明，对应激诱导的海马体体积变化的易感性和压力暴露前较大的海马体都会使个体在慢性应激后易患精神病理学。
