Duman Ronald S, Monteggia Lisa M
Division of Molecular Psychiatry, Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06508, USA.
Biol Psychiatry. 2006 Jun 15;59(12):1116-27. doi: 10.1016/j.biopsych.2006.02.013. Epub 2006 Apr 21.
There is a growing body of evidence demonstrating that stress decreases the expression of brain-derived neurotrophic factor (BDNF) in limbic structures that control mood and that antidepressant treatment reverses or blocks the effects of stress. Decreased levels of BDNF, as well as other neurotrophic factors, could contribute to the atrophy of certain limbic structures, including the hippocampus and prefrontal cortex that has been observed in depressed subjects. Conversely, the neurotrophic actions of antidepressants could reverse neuronal atrophy and cell loss and thereby contribute to the therapeutic actions of these treatments. This review provides a critical examination of the neurotrophic hypothesis of depression that has evolved from this work, including analysis of preclinical cellular (adult neurogenesis) and behavioral models of depression and antidepressant actions, as well as clinical neuroimaging and postmortem studies. Although there are some limitations, the results of these studies are consistent with the hypothesis that decreased expression of BDNF and possibly other growth factors contributes to depression and that upregulation of BDNF plays a role in the actions of antidepressant treatment.
越来越多的证据表明，压力会降低控制情绪的边缘结构中脑源性神经营养因子（BDNF）的表达，而抗抑郁治疗可逆转或阻断压力的影响。BDNF以及其他神经营养因子水平的降低，可能导致某些边缘结构萎缩，包括在抑郁症患者中观察到的海马体和前额叶皮质。相反，抗抑郁药的神经营养作用可以逆转神经元萎缩和细胞丢失，从而有助于这些治疗的疗效。这篇综述对源于此项研究的抑郁症神经营养假说进行了批判性审视，包括对临床前细胞（成体神经发生）以及抑郁症和抗抑郁药作用的行为模型的分析，以及临床神经影像学和尸检研究。尽管存在一些局限性，但这些研究结果与以下假说一致：BDNF以及可能其他生长因子的表达降低导致抑郁症，而BDNF的上调在抗抑郁治疗作用中发挥作用。
