Katz M M, Maas J W, Frazer A, Koslow S H, Bowden C L, Berman N, Swann A C, Stokes P E
Department of Psychiatry, Albert Einstein College of Medicine-Montefiore Medical Center, Bronx, New York 10467.
Neuropsychopharmacology. 1994 Oct;11(2):89-100. doi: 10.1038/npp.1994.38.
Despite cumulative evidence that the tricyclic drugs result in significant changes in the functioning of brain serotonergic (5-HT) and nordrenergic (NE) systems, such changes have not been found to be associated with recovery from depression. Based upon evidence that the 5-HT and NE systems were associated with different emotions, it was hypothesized that changes in these systems were associated with different components of behavior in drug-responsive patients and not with changes in the "whole" disorder. Findings from this multihospital study of 104 unipolar and bipolar depressed patients showed early drug-associated reductions in anxiety and hostility in treatment responders to precede changes in motor retardation and depressed mood. Adopting this approach of looking for relationships between changes in components of major depression and changes in neurotransmitter system function, decreases in 5-HT and NE metabolite concentrations in cerebrospinal fluid (CSF) in patients treated with tricyclics, were found to be correlated with changes in specific behaviors. Results indicated the following: (1) drug-induced changes in the 5-HT system to be associated with mood aspects, notably anxiety, and depressed mood; changes in NE primarily with the psychomotor, secondarily with the mood components of the depressed state; (2) the pattern of relationships between changes in 5-HT and in mood in the unipolar was different than that in the bipolar subtype. The results indicate that in determining the relationships of biochemical changes to behavioral ones, that it is important to take into account the type of depression (bipolar or unipolar), as well as examining individually and over time those components that make up the disorder of depression. These results support evidence that tricyclics have multiple behavioral actions, that response is mediated through changes in specific behaviors and that this approach warrants further application in prospective studies of antidepressant drug mechanisms and their therapeutic actions.
尽管有越来越多的证据表明三环类药物会导致大脑血清素能（5 - HT）和去甲肾上腺素能（NE）系统的功能发生显著变化，但尚未发现这些变化与抑郁症的康复有关。基于5 - HT和NE系统与不同情绪相关的证据，有人推测这些系统的变化与药物反应性患者行为的不同组成部分有关，而与“整体”疾病的变化无关。这项对104名单相和双相抑郁症患者进行的多医院研究结果显示，在治疗有反应的患者中，与药物相关的焦虑和敌意的早期减轻先于运动迟缓及抑郁情绪的变化。采用这种寻找重度抑郁症组成部分变化与神经递质系统功能变化之间关系的方法，发现接受三环类药物治疗的患者脑脊液（CSF）中5 - HT和NE代谢物浓度的降低与特定行为的变化相关。结果表明：（1）药物引起的5 - HT系统变化与情绪方面相关，尤其是焦虑和抑郁情绪；NE的变化主要与精神运动方面相关，其次与抑郁状态的情绪组成部分相关；（2）单相抑郁症中5 - HT变化与情绪之间的关系模式与双相亚型不同。结果表明，在确定生化变化与行为变化的关系时，考虑抑郁症的类型（双相或单相）很重要，同时还要单独并随着时间检查构成抑郁症的那些组成部分。这些结果支持了以下证据：三环类药物具有多种行为作用，反应是通过特定行为的变化介导的，并且这种方法值得在抗抑郁药物机制及其治疗作用的前瞻性研究中进一步应用。
