Charney D S
Department of Psychiatry, Yale University School of Medicine, New Haven, Conn 06519, USA.
J Clin Psychiatry. 1998;59 Suppl 14:11-4.
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.
中枢神经系统（CNS）中去甲肾上腺素能和5-羟色胺能功能的改变与抑郁症的病理生理学及抗抑郁药物的作用机制有关。基于中枢神经系统中去甲肾上腺素和5-羟色胺代谢的变化，推测可能存在对去甲肾上腺素和5-羟色胺再摄取抑制剂反应不同的患者亚组。α-甲基对酪氨酸（AMPT）可使脑内儿茶酚胺迅速耗竭，已被用作去甲肾上腺素能探针，以检验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基础的假说。脑内5-羟色胺依赖于必需氨基酸色氨酸的血浆水平。以无色氨酸氨基酸饮料形式进行的快速色氨酸耗竭已被用作5-羟色胺能探针，以识别对治疗有反应的患者亚组。使用这些探针，我们最近研究了在3种不同状态下，脑单胺浓度降低对接受各种5-羟色胺选择性再摄取抑制剂（SSRI）或相对去甲肾上腺素选择性抗抑郁药地昔帕明治疗的抑郁症患者的行为影响：未服药且抑郁；服用抗抑郁药病情缓解；未服药且病情缓解。一系列研究结果证实了单胺在调节抑郁情绪中的重要性，但也表明其他脑神经系统在抑郁症病理生理学中的作用可能比以前认为的更为重要。去甲肾上腺素能和5-羟色胺能探针可能及时用于识别抑郁症患者亚组确定哪些患者可能对新型选择性去甲肾上腺素再摄取抑制剂或SSRI有不同反应。
