Hirschfeld R M
Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, Galveston 77555-0188, USA.
J Clin Psychiatry. 2000;61 Suppl 6:4-6.
The symptoms of depression can be improved by agents that act by various mechanisms to increase synaptic concentrations of monoamines. This finding led to the adoption of the monoamine hypothesis of depression, first put forward over 30 years ago, which proposes that the underlying biological or neuroanatomical basis for depression is a deficiency of central noradrenergic and/or serotonergic systems and that targeting this neuronal lesion with an antidepressant would tend to restore normal function in depressed patients. The hypothesis has enjoyed considerable support, since it attempts to provide a pathophysiologic explanation of the actions of antidepressants. However, in its original form it is clearly inadequate, as it does not provide a complete explanation for the actions of antidepressants, and the pathophysiology of depression itself remains unknown. The hypothesis has evolved over the years to include, for example, adaptive changes in receptors to explain why there should be only a gradual clinical response to antidepressant treatment when the increase in availability of monoamines is rapid. Still, the monoamine hypothesis does not address key issues such as why antidepressants are also effective in other disorders such as panic disorder, obsessive-compulsive disorder, and bulimia, or why all drugs that enhance serotonergic or noradrenergic transmission are not necessarily effective in depression. Despite these limitations, however, it is clear that the development of the monoamine hypothesis has been of great importance in understanding depression and in the development of safe and effective pharmacologic agents for its treatment.
抑郁症的症状可通过多种作用机制增加单胺类神经递质突触浓度的药物得到改善。这一发现促使人们采用了抑郁症的单胺假说，该假说于30多年前首次提出，其认为抑郁症潜在的生物学或神经解剖学基础是中枢去甲肾上腺素能和/或5-羟色胺能系统功能不足，且使用抗抑郁药针对这种神经元损伤进行治疗，有望使抑郁症患者恢复正常功能。这一假说得到了相当多的支持，因为它试图为抗抑郁药的作用提供病理生理学解释。然而，其最初形式显然并不充分，因为它没有为抗抑郁药的作用提供完整解释，而且抑郁症本身的病理生理学仍然未知。多年来，该假说不断演变，例如纳入了受体的适应性变化，以解释为何单胺类神经递质可用性迅速增加时，抗抑郁治疗的临床反应却较为缓慢。即便如此，单胺假说仍未解决一些关键问题，比如为何抗抑郁药对惊恐障碍、强迫症和贪食症等其他疾病也有效，或者为何所有增强5-羟色胺能或去甲肾上腺素能传递的药物不一定对抑郁症有效。尽管存在这些局限性，但单胺假说的发展对于理解抑郁症以及开发安全有效的治疗药物显然具有重要意义。
