MONOAMINE RECEPTORS: EFFECTS OF DEPRESSION & TREATMENT

因为记录在案的正常衰老对儿茶酚胺水平的影响 和β受体功能；因为儿茶酚胺的潜在作用 重度抑郁障碍中的β受体与慢性抑郁症的作用 躯体抗抑郁治疗下调β受体；以及 由于严重抑郁症的发病率随着年龄的增长而增加， 中枢和外周β受体功能与正常的关系 衰老和抑郁是人们相当感兴趣的问题。因为它不是 直接研究人类中枢β受体功能是可行的，我们有 开发了测量两种β受体结合的简便方法 参数和异丙肾上腺素诱导的完整人cAMP的产生 淋巴细胞在相似的检测条件下。我们建议研究 ~(125)I-氰基吲哚结合参数与~(125)I的关系 异丙肾上腺素诱导的cAMP产生：衰老；性别；重度抑郁 精神障碍伴忧郁症；抗抑郁治疗的效果。 由于淋巴细胞上的受体可能受到循环激素的调节， 血浆和24小时尿儿茶酚胺和皮质醇水平(这是 可能因衰老或抑郁而改变)将进行检测。患者会 在无药物基线期间进行研究，以与年龄和 性别匹配的对照组受试者。这些措施将在每周进行一次。 电休克治疗与丙咪嗪治疗两组住院患者的疗效观察 对淋巴细胞β受体功能或恢复正负的影响 慢性三环治疗。 我们的初步数据表明：β受体的状态依赖性减少 无毒抑郁症患者的淋巴细胞敏感性：一个年龄 对β受体连接的腺苷环化酶敏感性的影响但不影响 125I-CYP结合参数；性别对结合和cAMP的影响 回应。这项研究将检验和推广这些初步发现，并 测试它们作为诊断抑郁症的生化手段的适用性 并监测抗抑郁药物治疗效果和预测预后 严重的抑郁症与忧郁症，以及增加我们对 正常衰老对β受体的影响。此外，它的敏感度 β受体对血浆体液因子(儿茶酚胺和 Crotisol)将在以下方面进行对比：年轻和老年对照组；男性和 女性；在抑郁和愉悦的患者中。

Because of the documented effects of normal aging upon catecholamine levels and beta receptor function; because of the potential role of catecholamines and beta receptors in Major Depressive Disorders and the action of chronic somatic antidepressant treatment in downregulating beta receptors; and since the incidence of Major Depression increases with aging, studies of the relationship of central and peripheral beta receptor function to normal aging and depression are of considerable interest. Since it is not feasible to directly study central beta receptor function in man, we have developed convenient assays for measuring both beta receptor binding parameters and isoproterenol-induced cAMP production in intact human lymphocytes under similar assay conditions. We propose to study the relationship of 125I-cyanopindolol binding parameters and isoproterenol-induced cAMP production to: aging; sex; Major Depressive Disorder with melancholia; and the effect of antidepressant treatment. Since receptors on lymphocytes may be modulated by circulating hormones, plasma and 24 hour urinary catecholamine and cortisol levels (which are potentially altered by aging or depression) will be assayed. Patients will be studied during a drug-free baseline period for comparison with age and sex-matched control subjects. Measures will be repeated weekly throughout treatment by ECT or imipramine in two groups of inpatients to study the effects upon lymphocyte beta receptor function or recovery plus or minus chronic tricyclic treatment. Our preliminary data suggest: a state-dependent reduction in beta receptor sensitivity in lymphocytes in drug-free patients with melancholia: an age effect upon beta receptor-linked adenylate cyclase sensitivity but not 125I-CYP binding parameters; and a sex effect upon both binding and cAMP response. This study will test and extend these preliminary findings and test their applicability as a biochemical means of diagnosis of depression and monitering antidepressant treatment effect and predicting outcome in major depression with melancholia, as well as increase our understanding of normal aging effects upon beta receptors. In addition, the sensitivity of beta receptors to modulation by plasma humoral factors (catecholamines and crotisol) will be contrasted in: young and old controls; males and females; and in patients while depressed and euthymic.