TYRAMINE SULFATE EXCRETION--TRAIT MARKER IN DEPRESSION

酪胺硫酸盐排泄——抑郁症的特征标志

• 批准号: 3376877
• 负责人: THOMAS B COOPER
• 金额: $ 10.1万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-01 至 1990-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3376877
• 关键词: chemical conjugate; clinical depression; depression; diagnosis design /evaluation; excretion; human subject; mental disorder diagnosis; neuropsychological tests; pharmacokinetics; platelets; sulfates; sulfotransferase; tyramine; urine

Discovery of trait markers for psychiatric disorders is an urgently sought but elusive goal. Trait markers with acceptable levels of sensitivity and specificity would not only facilitate differential diagnosis and choice of suitable treatment, but would help illuminate etiological factors and promote programs of primary prevention. There are currently no validated "trait" markers for depression. A promising area of inquiry is the tyramine test. Sandler et al. 1 reported that patients with endogenous unipolar depression excrete significantly lower amounts of urinary sulfate conjugated tyramine in response to an oral tyramine load than normals and that this apparent conjugation deficit persists after recovery from depression, suggesting a "trait" marker. Ghose and Coppen 2 observed an enhanced pressor response to intravenous tyramine in depressives. Their data suggest that the increased tyramine sensitivity persisted after recovery from depression (another trait marker?). Patient with depression will be re- challenged with oral tyramine during depression, while taking conventional antidepressants and after recovery to determine state independent, persistence of the deficit and the effect of medication on the reproducibility of the test. Normals will be re-tested at similar time intervals as controls. We hypothesize that the most likely mechanisms for the reduced tyramine sulfate excretion are an increase in monoamine oxidase or a defect in sulfate conjugation. We intend to test this in depressives and normal controls by: (1) measurement of platelet monoamine oxidase and phenolsulfotransferase activity; (2) determination of the pharmacokinetic profiles of tyramine-o-sulfate in plasma and urine. We also propose to determine whether there is any correlation between the apparent tyramine sulfate conjugation defect and enhanced intravenous tyramine dose-pressor response as putative trait markers by conducting both of these tests in the same subjects.

发现精神障碍的特质标记是一个迫切的问题。 追求但难以实现的目标。 具有可接受水平的性状标记 敏感性和特异性不仅有助于鉴别 诊断和选择适当的治疗，但将有助于 阐明原发性肝癌病因及促进方案 预防 目前还没有有效的“性状”标记， 萧条 一个有希望的调查领域是酪胺测试。 Sandler等人1报告，内源性单极性心律失常患者 抑郁症患者的尿硫酸盐排泄量显著降低 结合酪胺对口服酪胺负荷的响应， 正常，这种明显的共轭赤字持续后， 从抑郁症中恢复，这表明了一个“特征”标记。 Ghose和 Coppen 2观察到静脉注射 抑郁症中的酪胺。 他们的数据表明， 从抑郁症中恢复后，酪胺敏感性仍然存在 （另一个特征标记？）。 患有抑郁症的患者将被重新- 在抑郁症期间口服酪胺，同时服用 常规抗抑郁药和恢复后，以确定 国家独立，赤字的持续性和 药物对测试的可重复性。 常态将是 以与对照相似的时间间隔重新测试。 我们假设 酪胺硫酸盐减少的最可能机制 排泄是单胺氧化酶的增加或 硫酸盐共轭 我们打算在抑郁症患者中进行测试， 正常对照：（1）血小板单胺测定 氧化酶和酚磺基转移酶活性;（2） 血浆中酪胺-o-硫酸盐的药代动力学特征， 尿 我们亦建议确定是否有任何 表观酪胺硫酸盐结合 静脉酪胺剂量-升压反应缺陷和增强 作为假定的性状标记，通过进行这两个测试， 同样的主题。