HUMAN NEUROENDOCRINE STUDIES

这项提案试图解决这样一个问题：监管失衡 边缘-下丘脑-垂体-肾上腺(LHPA)轴的观察 抑郁是压力的结果，这种压力要么促使 抑郁和/或由其引起的，还是LHPA轴发挥更大的作用 在抑郁症生物学中的基础作用？如果是后者 正确地说，我们假设那些容易患上 抑郁症对心理压力的反应可能不同于 受内分泌相关的监测，而且它们可能不仅在 在插曲的时候，也在插曲的时候。这会表明 充满负面影响的信息可能会被记住 与正常对照组相比，抑郁症患者的情况有所不同。 我们建议通过对抑郁症患者进行测试来检验这些想法。 走出剧集，面对社交压力源，测试他们对此的反应 在内分泌方面，他们终止这种反应的速度有多快，以及如何 嗯，他们习惯了它的重复呈现。我们还将使用 新设计的记忆测试对比了记忆中性的能力 对比负面材料，并询问抑郁的受试者是否在 或在剧集之外，显示与控件在处理方式上的差异 情感素材。此外，我们还将在节目中测试受试者 在纯粹的神经内分泌水平上使用一些敏感的挑战 我们已经设计并验证了，我们认为这反映了 LHPA轴的神经元而不是外周成分--这些 将包括在晚上节奏最低的时候进行甲孕酮测试 在那里我们观察到驾驶水平的严重失调，以及一项测试 早上的快速反馈，在节奏的顶峰，在那里我们 在糖皮质激素反馈方面出现了障碍。 解决这一中心问题的一个补充方法是研究 一组经历着非常紧张的生活环境的受试者(基因 检测家族性乳腺癌基因-BRCA1，以确定是否 不是它们携带了一种突变，这种突变使它们有近90%的机会 罹患乳腺癌和/或卵巢癌)；评估其 在这一点上的神经内分泌情况；并决定是否 与患有严重抑郁症的人相似。然后我们会问 神经内分泌异常是否与个人 或有严重抑郁症的家族史，或随后的 抑郁或情绪障碍的发生，根据6个月的确定 后续行动。 总而言之，这一系列研究应该会揭示出 抑郁症与应激失调的关系 响应性。

This proposal attempts to address the question: is the dysregulation of the Limbic-Hypothalamo-Pituitary-Adrenal (LHPA) Axis observed in depression a result of the stress which either precipitated the depression and/or resulted from it, or does the LHPA axis play a more fundamental role in the biology of depression? If the latter is correct, we would hypothesize that individuals who are prone to depression may respond to psychological stressors differently as monitored by endocrine correlates, and that they may do so not only when in episode, but also when out of episode. It would suggest that information which is laden with negative affect may be remembered differently by depressive individuals, as compared to normal controls. We propose to test these ideas by subjecting depressed patients, in and out of episode, to a social stressor and testing how they respond to it endocrinologically, how rapidly they terminate this response, and how well they habituate to its repeated presentation. We shall also use a newly devised memory test which contrast the ability to remember neutral vs. negative material, and ask whether depressed subjects, be they in or out of episode, show differences from controls in the way they handle emotional material. In addition, we shall test subjects out of episode at the purely neuroendocrine level using some sensitive challenges which we have devised and validated, and which we believe are reflective of the neuronal rather than the peripheral elements of the LHPA axis--these will include a metyrapone test in the evening at the nadir of the rhythm where we observe substantial dysregulation in drive level, and a test of fast feedback in the morning, at the peak of the rhythm, where we have shown a disturbance in glucocorticoid feedback. A complementary approach to addressing this central question is to study a group of subjects undergoing a very stressful life situation ( genetic test for a familial Breast Cancer Gene-BRCA1, to determine whether or not they carry a mutation which gives them an almost 90% chance of developing breast and/or ovarian cancer); evaluating their neuroendocrine profile at that point; and determining whether it resembles that of individuals with major depression. We shall then ask whether an abnormal neuroendocrine profile is correlated with a personal or a family history of major depression, or with the subsequent occurrence of depression or mood disorders, as determined with a 6 month follow-up. Together, this series of studies should shed light on the extent of the relationship between major depression and the dysregulation of stress responsiveness.