Feldmann Robert E, Sawa Akira, Seidler Guenter H
Department of Physiology and Pathophysiology, Division of Systems Physiology, University of Heidelberg, Im Neuenheimer Feld 326, D-69120 Heidelberg, Germany.
J Psychiatr Res. 2007 Nov;41(9):713-23. doi: 10.1016/j.jpsychires.2006.06.007. Epub 2006 Aug 4.
Mood disorders compose a considerable portion of the worldwide prevailing diseases with high suicide rates and urgent demand for novel therapeutic interventions as efficacious treatment is still lacking. Depression is thought to feature distinct morphological correlatives in the brain and has recently been linked to adult neurogenesis (NG) in the hippocampal formation. Numerous findings give rise to the hypothesis that depression and declining NG in the hippocampus may be causally connected. This implies that depressive symptoms could originate from impairments in NG and, vice versa, that improved NG could mediate antidepressant action and alleviate symptoms. Thus, great hopes rest on the question whether the observed increase in NG following antidepression treatment may have the potential to become a novel drug target and specific mechanism in the development of the next generation of antidepressants that specifically involves targeting of neuropoetic factors in addition to their "traditional" effects as modulators of synaptic transmission. Along the still hypothetical association of depression and NG, however, several controversies and unresolved questions exist with respect to the presently available data and interpretation. This article highlights and summarizes some of the most pressing issues and identifies the crucial ones that await urgent clarification and resolving. Without their reliable answering, the fascinating notion of a neurogenic basis for depression will remain to be greatly speculative.
情绪障碍在全球流行疾病中占相当大的比例，自杀率高，且由于仍缺乏有效的治疗方法，迫切需要新的治疗干预措施。抑郁症被认为在大脑中具有独特的形态学关联，最近还与海马结构中的成年神经发生（NG）有关。众多研究结果引发了这样一种假说，即抑郁症与海马体中NG的减少可能存在因果关系。这意味着抑郁症状可能源于NG的损伤，反之，NG的改善可能介导抗抑郁作用并缓解症状。因此，人们寄厚望于抗抑郁治疗后观察到的NG增加是否有可能成为新一代抗抑郁药开发中的新药物靶点和特定机制，新一代抗抑郁药除了具有作为突触传递调节剂的“传统”作用外，还特别涉及对神经生成因子的靶向作用。然而，沿着抑郁症与NG这一仍属假设的关联，就目前可得的数据和解释而言，存在一些争议和未解决的问题。本文重点介绍并总结了一些最紧迫的问题，并确定了亟待澄清和解决的关键问题。如果这些问题得不到可靠的答案，抑郁症具有神经源性基础这一引人入胜的概念仍将极具推测性。
