The outlines of a theory of the pathophysiology of depression are presented. The classic monoamine theory of depression as well as its more recent elaborations suggests that a deficit in monoamine neurotransmitters in the synaptic cleft is the primary cause of depression. We suggest that the primary defect emerges in the regulation of firing rates in brainstem monoaminergic neurons, which brings about a decrease in the tonic release of neurotransmitters in their projection areas, an increase in postsynaptic sensitivity and, concomitantly, exaggerated responses to acute increases in presynaptic firing rate and transmitter release. We propose that the initial defect involves, in particular, the noradrenergic innervation from the locus coeruleus, which in turn leads to dysregulation of 5-HT-ergic and dopaminergic neurotransmission.

译文

提出了抑郁症病理生理学理论的概述。抑郁症的经典单胺理论及其最近的阐述表明,突触间隙中单胺神经递质的缺陷是抑郁症的主要原因。我们建议,主要缺陷出现在脑干单胺能神经元放电速率的调节中,这导致其投射区域神经递质的强直释放减少,突触后敏感性增加,以及伴随而来的对急性增加的过度反应突触前放电速率和递质释放。我们建议最初的缺陷尤其涉及来自蓝斑的去甲肾上腺素能神经支配,这反过来又导致5-ht能和多巴胺能神经传递的失调。

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