Monoamine dysfunction and the pathophysiology and treatment of depression.
Monoamine dysfunction and the pathophysiology and treatment of depression.
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发表时间：
1998-04
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通讯作者：
D. Charney
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作者：
D. Charney
中枢神经系统（CNS）去甲肾上腺素能和血清素能功能的改变与抑郁症的病理生理和抗抑郁药物的作用机制有关。根据去甲肾上腺素和5 -羟色胺在中枢神经系统代谢的变化，假设可能存在对去甲肾上腺素和5 -羟色胺再摄取抑制剂有不同反应的患者亚组。α -甲基副酪氨酸（AMPT）引起脑内儿茶酚胺的快速消耗，已被用作去甲肾上腺素能探针，以验证通过儿茶酚胺系统的神经传递变化可能是去甲肾上腺素再摄取抑制剂治疗反应的基础。脑血清素依赖于必需氨基酸色氨酸的血浆水平。快速色氨酸耗竭，以不含色氨酸的氨基酸饮料的形式，已被用作5 -羟色胺能探针，以确定治疗反应的患者亚群。使用这些探针，我们最近研究了在3种不同状态下，使用各种血清素选择性再摄取抑制剂（SSRIs）或相对去甲肾上腺素选择性抗抑郁药地西帕明治疗的抑郁症患者脑单胺浓度降低的行为影响：无药和抑郁；服用抗抑郁药物缓解期；而且在缓解期没有药物。一系列的研究结果证实了单胺在调节抑郁情绪中的重要性，但也表明，在抑郁症的病理生理学中，其他脑神经系统可能比以前认为的更重要。去甲肾上腺素能和血清素能探针可以及时用于识别抑郁症患者的亚群，以确定哪些患者可能对新的选择性去甲肾上腺素再摄取抑制剂或SSRIs有不同的反应。
Alterations in noradrenergic and serotonergic function in the central nervous system (CNS) have been implicated in the pathophysiology of depression and the mechanism of action of antidepressant drugs. Based on changes in norepinephrine and serotonin metabolism in the CNS, it has been postulated that subgroups of patients with differential responses to norepinephrine and serotonin reuptake inhibitors may exist. Alpha-methylparatyrosine (AMPT), which causes rapid depletion of brain catecholamines, has been used as a noradrenergic probe to test the hypothesis that changes in neurotransmission through the catecholamine system may underlie the therapeutic response to norepinephrine reuptake inhibitors. Brain serotonin is dependent on plasma levels of the essential amino acid tryptophan. Rapid tryptophan depletion, in the form of a tryptophan-free amino acid drink, has been used as a serotonergic probe to identify therapeutically responsive subsets of patients. Using these probes, we have recently examined the behavioral effects of reduced concentrations of brain monoamines on depressed patients treated with a variety of serotonin selective reuptake inhibitors (SSRIs) or the relatively norepinephrine-selective antidepressant desipramine, during 3 different states: drug-free and depressed; in remission on antidepressant drugs; and drug-free in remission. The results of a series of investigations confirm the importance of monoamines in the mediation of depressed mood, but also suggest that other brain neural systems may have more of a primary role than previously thought in the pathophysiology of depression. Noradrenergic and serotonergic probes may be used in time to identify subsets of depressed patients to determine which patients might respond differentially to the new selective norepinephrine reuptake inhibitors or SSRIs.