Malberg Jessica E
Wyeth Research, Princeton, NJ 08543, USA.
J Psychiatry Neurosci. 2004 May;29(3):196-205.
In the dentate gyrus of the hippocampus, cell birth and maturation into neurons, or neurogenesis, occur throughout the lifetime of animals and humans. Multiple factors have been shown to regulate adult neurogenesis, and a number of findings in this field have had a large impact on basic and clinical research in depression. It has been reported that both physical and psychosocial stress paradigms, as well as some animal models of depression, produce a decrease in hippocampal cell proliferation and neurogenesis. Conversely, long-term, but not short-term, treatment with different classes of antidepressant drug increases cell proliferation and neurogenesis. Patients with depressive disorders or post-traumatic stress disorder have reduced hippocampal volume. Given this interaction of stress, depression and neurogenesis, a current hypothesis is that reduced adult hippocampal cell proliferation or neurogenesis may be involved in the pathophysiology of depression and that reversal or prevention of the decrease in neurogenesis may be one way in which the antidepressant drugs exert their effects. Research from this emerging field will further our understanding of the effects of stress and depression on the brain and the mechanism of action of antidepressant drugs.
在海马体的齿状回中,细胞生成并成熟为神经元,即神经发生,这一过程贯穿动物和人类的一生。多种因素已被证明可调节成体神经发生,该领域的一些研究结果对抑郁症的基础和临床研究产生了重大影响。据报道,生理和心理社会应激范式以及一些抑郁症动物模型都会导致海马体细胞增殖和神经发生减少。相反,不同类别的抗抑郁药物进行长期(而非短期)治疗可增加细胞增殖和神经发生。患有抑郁症或创伤后应激障碍的患者海马体体积减小。鉴于应激、抑郁和神经发生之间的这种相互作用,目前的一个假说是,成体海马体细胞增殖或神经发生减少可能参与了抑郁症的病理生理学过程,而逆转或预防神经发生的减少可能是抗抑郁药物发挥作用的一种方式。这一新兴领域的研究将加深我们对应激和抑郁对大脑的影响以及抗抑郁药物作用机制的理解。