TYRAMINE SULFATE EXCRETION--TRAIT MARKER IN DEPRESSION

发现精神障碍的特征标记是当务之急 追求但难以捉摸的目标。具有可接受水平的性状标记 敏感性和特异性不仅有助于区分 诊断和选择合适的治疗方法，但会有所帮助 阐明小儿麻痹症的致病因素及促进方案 预防。目前没有经过验证的“特征”标记 抑郁症。酪胺试验是一个很有前途的调查领域。 Sandler等人的研究成果。1报道内源性单相患者 抑郁症患者尿硫酸盐排泄量显著减少 结合酪胺对口服酪胺负荷的反应比 并且这种明显的结合缺陷在 从抑郁中恢复过来，表明这是一种“特质”标记。Ghose和 Copen 2观察到静脉注射后升压反应增强 抑郁症中的酪胺。他们的数据表明，增加的 从抑郁中恢复后对酪胺的敏感性持续存在 (另一个性状标记？)抑郁症患者将被重新治疗 在抑郁期间口服酪胺挑战，同时服用 常规抗抑郁药及康复后测定 国家独立性、赤字的持久性和 药物对检测的重复性有影响。法线将是 以与对照组相似的时间间隔重新测试。我们假设 还原的酪胺硫酸盐最可能的机制是 排泄是单胺氧化酶的增加或 硫酸盐结合。我们打算在抑郁症患者中测试这一点 正常对照组：(1)测定血小板单胺 氧化酶和酚磺基转移酶活性；(2) 酪胺-o-硫酸盐在人体内的药代动力学 尿液。我们还建议确定是否有任何 硫酸酪胺表观结合度之间的相关性 缺陷和增强的静脉注射酪胺剂量-升压反应 作为假定的性状标记，通过在 同样的主题。

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.