MONOAMINE RECEPTORS: EFFECTS OF DEPRESSION & TREATMENT

β-脱敏作用假说的一个推论 肾上腺素能结合或反应性是最终的共同之处 产生抗抑郁作用的途径是 抑郁症的发病机制涉及β-肾上腺素能 受体复合体。我们发现)降低了对 无毒状态下的淋巴细胞β-肾上腺素能受体复合体 内源性抑郁症住院患者。次敏感的贝塔- 反应与一种更严重的、反复出现的 DST上的抑郁和非抑制；b)治疗 三环类抗抑郁药导致β-受体激动剂的再增敏 肾上腺素能受体复合体。建议将这些条款延长 研究人员： (一)进一步明确临床、神经内分泌和生化 钝化淋巴细胞β-肾上腺素能反应性的相关性 抑郁症患者； (2)阐明β受体异常的机制 (I)激动剂对抑郁症患者受体水平功能的影响 用于评估受体功能的结合研究，(Ii)NS的分析 和镍偶联蛋白以及(III)体外和体内的测定 突触非依赖性淋巴细胞β-受体的体内下调能力 受体； (3)间接评估突触后β1-肾上腺素能受体 通过测量心率在增加后的变化 儿茶酚胺水平； (4)调节受体的因素研究，包括(一) 仰卧位和体位挑战后血浆NE和EPI的变化 化验及24小时尿排泄量及(Ii) 治疗前后血、尿皮质醇水平 地塞米松； (5)在住院期间对病人进行纵向研究 并在门诊就诊六个月以确定治疗效果 (去甲替林)。测试将在6个月后进行 戒毒的欣快症患者的治疗已经完成， 管制以容许区分国家和- 性状依赖以及药物引起的生物差异。 初步数据表明淋巴细胞β-1再敏化 三环治疗后抑郁症患者的肾上腺素能反应性 治疗部分依赖于地塞米松的正常化。 对美沙酮耐药。重新敏化的基础将是 研究与心脏β-肾上腺素能反应性的关系， NT药物水平、临床改善、HYPAC状态、血浆CAs 级别将被确定。这些研究应该提供新的 对单相的潜在神经生物学亚型的洞察 内源性抑郁，β-肾上腺素能受体在抑郁症中的作用 抑郁症的病理生理学基础及其作用机制 三环类抗抑郁药。

A corollary of the hypothesis that desensitization of beta- adrenergic binding or responsiveness represents a final common pathway for generating an antidepressant effect is that the pathogenesis of depressive disorders involves the beta-adrenergic receptor complex. We have found a) diminished responsiveness of the lymphocyte beta-adrenergic receptor complex in drug-free inpatients with endogenous depression. Subsensitive beta- responses were associated with a more severe, recurrent form of depression and nonsuppression on the DST; b) treatment with tricyclic antidepressants resulted in resensitization of beta- adrenergic receptor complexes. It is proposed to extend these studies by: (1) further defining clinical, neuroendocrine and biochemical correlates of blunted lymphocyte beta-adrenergic responsiveness in depressed patients; (2) clarifying the mechanism of abnormalities in beta-receptor function in depressed patients at the receptor level by (i) agonist binding studies to assess receptor function, (ii) assays of the Ns and Ni coupling proteins and (iii) measurement of in vitro and in vivo downregulability of synapse independent lymphocyte beta- receptors; (3) indirectly assessing postsynaptic beta 1 - adrenergic receptors by measurement of heart rate change after an increase in catecholamine levels; (4) studies of factors that regulate the receptor including (i) plasma NE and EPI while supine and after a postural challenge test as well as 24 hour urinary excretion levels of CAs and (ii) plasma and urinary cortisol levels before and after dexamethasone; (5) studying patients longitudinally both during the inpatient phase and six months as an outpatient to determine treatment effects (nortriptyline). Testing will be carried out after 6 months of treatment is completed in drug-free euthymic patients and controls to permit a distinction to be made between state-and- trait dependent as well as drug-induced biological differences. Preliminary data suggest resensitization of lymphocyte beta- adrenergic responsiveness in depressed patients after tricyclic treatment is partly dependent on normalization of dexa- methasone resistance. The basis for resensitization will be studied and relationships to cardiac beta-adrenergic responsivity, NT drug level, clinical improvement, HYPAC status, plasma CAs levels will be determined. These studies should provide new insights into potential neurobiological subtypes of unipolar endogenous depression, the role of beta-adrenergic receptors in the pathophysiology of depression, and the mechanism of action of tricyclic antidepressants.