Centre for Neuroscience, Swammerdam Institute of Life Sciences, University of Amsterdam, P.O. box 94214, 1090 GE Amsterdam, The Netherlands.
Neuropharmacology. 2010 May;58(6):940-9. doi: 10.1016/j.neuropharm.2010.01.012. Epub 2010 Feb 9.
Imaging studies have consistently documented hippocampal volume reductions in depression. Although depressive disorders are traditionally considered to have a neurochemical basis, recent studies suggest that impairments of structural plasticity contribute to the volume reductions and the related cognitive changes. This might result from repeated periods of stress that are a wellknown risk factor for depression. Adult neurogenesis is a prominent example of neuroplasticity that in rodents, is reduced by stress but stimulated by antidepressant drugs. Although reductions in neurogenesis have been proposed to contribute to the etiology of depression, only two studies have so far examined hippocampal cytogenesis in depression, but this was in a limited number of subjects with considerable interindividual variation, and these studies came to different conclusions. We therefore collected hippocampal tissue of 10 elderly control subject and 10 well-matched depressed patients that were highly comparable in terms of age, sex, pH-CSF and postmortem delay, and tested whether the numbers of MCM2-positive progenitors and PH3-positive proliferating cells were altered by depression or antidepressant treatment. A significant reduction was found in MCM2-, but not PH3-immunopositive cells in depression. Although this result is consistent with the concept that structural plasticity is decreased in depression, we could not confirm that antidepressant drugs had a stimulatory effect on these cells. This discrepancy may relate to anatomical differences, in medication, to neurogenesis-independent mechanisms of antidepressant action, or the age of the patients that was higher than in previous studies. Whether the reduction is a cause or consequence of depression awaits to be determined.
影像学研究一致记录了抑郁症中海马体积的缩小。尽管抑郁障碍传统上被认为具有神经化学基础，但最近的研究表明，结构可塑性的损伤导致了体积缩小和相关的认知变化。这可能是由于压力的反复作用，压力是抑郁症的一个众所周知的危险因素。成年神经发生是神经可塑性的一个突出例子，在啮齿动物中，它会被压力所减少，但会被抗抑郁药物所刺激。尽管神经发生减少被认为有助于抑郁的病因，但目前只有两项研究在抑郁症中检查了海马细胞发生，但是这只在数量有限的个体中进行，并且存在相当大的个体间变异性，这些研究得出了不同的结论。因此，我们收集了 10 名老年对照组和 10 名匹配良好的抑郁症患者的海马组织，这些患者在年龄、性别、pH-CSF 和死后延迟方面高度匹配，并测试了 MCM2 阳性祖细胞和 PH3 阳性增殖细胞的数量是否因抑郁或抗抑郁治疗而改变。我们发现，MCM2 阳性细胞而不是 PH3 阳性细胞在抑郁症中显著减少。尽管这一结果与结构可塑性在抑郁症中减少的概念一致，但我们不能证实抗抑郁药物对这些细胞有刺激作用。这种差异可能与解剖学差异、药物、抗抑郁作用的神经发生无关机制或患者年龄较高有关，这些患者的年龄高于以前的研究。这种减少是抑郁的原因还是后果还有待确定。
