Jesberger J A, Richardson J S
Int J Neurosci. 1985 Jul;27(1-2):19-47. doi: 10.3109/00207458509149132.
The role of aberrant neurochemical substrates in the etiology of depression and the neurochemical mechanisms of antidepressant therapies have been the subjects of many hypotheses in the last 30 years. Pharmacological studies of early antidepressant drugs indicated that brain monoamines were significantly affected by these drugs and these led to the formulation of the biogenic amine hypothesis of depression. Although this hypothesis has been of heuristic value in the study of drug mechanisms and has provided a basis for screening drugs for antidepressant potential, deficiencies in it have become apparent. Neuroanatomical and neurochemical considerations favour the view that brain noradrenaline and serotonin systems may serve as bias adjusting systems for each other and numerous other neural systems. As a consequence of such a relationship, a primary defect in some other neural system would appear amplified in measurements of serotonin or noradrenaline. A possible site for this primary defect may be in membrane composition and function. Recent studies have found that typical and other antidepressant therapies have a pronounced effect on membrane lipids. Thus, in view of the important functions of membrane lipids and the fact that they have been linked to the initiation and development of a number of other disease processes, it is now suggested that consideration be given to them as playing primary causal roles in the etiology of depression and as a site of action for antidepressant drugs.
在过去30年里，异常神经化学底物在抑郁症病因学中的作用以及抗抑郁治疗的神经化学机制一直是众多假说的主题。早期抗抑郁药物的药理学研究表明，这些药物会显著影响脑单胺类物质，进而促成了抑郁症的生物胺假说。尽管该假说在药物机制研究中具有启发价值，并为筛选具有抗抑郁潜力的药物提供了基础，但其不足之处已日益明显。从神经解剖学和神经化学角度考虑，倾向于认为脑去甲肾上腺素和5-羟色胺系统可能相互作为偏倚调节系统，以及众多其他神经系统的偏倚调节系统。由于这种关系，在5-羟色胺或去甲肾上腺素测量中，其他一些神经系统的原发性缺陷可能会显得更为突出。这种原发性缺陷的一个可能部位可能在于膜的组成和功能。最近的研究发现，典型的及其他抗抑郁治疗对膜脂质有显著影响。因此，鉴于膜脂质的重要功能以及它们与许多其他疾病过程的起始和发展相关联这一事实，现在有人提出应考虑它们在抑郁症病因学中起主要因果作用，并作为抗抑郁药物的作用位点。
