HORMONE RHYTHMS--METABOLIC SIGNIFICANCE IN DEPRESSION

激素节律——抑郁症中的代谢意义

• 批准号: 3375050
• 负责人: Robert T. Rubin
• 金额: $ 10.6万
• 依托单位: LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-12-01 至 1992-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3375050
• 关键词: adolescence (12-20); adrenal glands; adrenocorticotropic hormone; adult human (21+); anticholinergic agent; arginine vasopressin; bioassay; blood chemistry; cholinergic agents; cholinergic receptors; corticotropin releasing factor; cortisol; disease /disorder classification; endocrine pharmacology; hormone regulation /control mechanism; human subject; hypothalamic pituitary axis; laboratory rat; longitudinal human study; magnetic resonance imaging; major depression; mental disorder diagnosis; metyrapone; neuroendocrine system; norepinephrine; physostigmine; pituitary adrenal axis; pituitary disorders; psychobiology; radioimmunoassay; scopolamine; statistics /biometry

This is a five-year revised renewal application to continue our studies of HPA axis hyperactivity in major depression. Our hypothesis, bases on our and others'data, is that this is a central nervous system (CNS)-driven HPA hyperactivity, with normal adaptive physiology of the axis itself (no qualitative dysregulation or defects), as reflected in a reduced ACTH response to CRH administration (corticotroph downregulation) and perhaps adrenal hyperresponsivity to ACTH administration and hypertrophy as well. To elucidate this, we are undertaking investigations of the HPA axis in major depressives and individually matched controls. ACTH(1-24) stimulation is being used to assess the sensitivity of the adrenal gland, ovine CRH (oCRH) stimulation is being used to assess corticotroph downregulation, and magnetic resonance (MR) imaging of the adrenal glands is being used for size determination. Hormone measures include plasma ACTH(1-39),ACTH(1-24). cortisol, and OCRH. Bioactive ACTH will be determined as well. Adolescent major depressives in different pubertal stages also are being studied to ascertain the contribution of development from early puberty through adulthood to HPA axis activity an responsivity depressive illness. We hypothesize that HPA axis hyperactivity in depression is state- dependent, and that following treatment, the hormone measures will return to normal in a consistent manner. Thus, all patients are being tracked through their treatment and are being studied a second time when are in remission and off medication for at least one month. The studies proposed herein should add to the evidence that HPA axis hyperactivity is a coordinated physiologic phenomenon resulting from increased CNS stimulation of CRH production. This will give even more impetus to the study of CNS neurotransmitter regulation of HPA axis activity in major depression, stress states, and other condiitons leading to increased HPA axis activity.

这是一份为期五年的修订续订申请，以继续我们的研究 重度抑郁症中的 HPA 轴过度活跃。 我们的假设基于我们 和其他人的数据一样，这是一个中枢神经系统（CNS）驱动的 HPA 多动症，轴本身具有正常的适应性生理机能（无 质的失调或缺陷），如 ACTH 减少所反映 对 CRH 给药的反应（促肾上腺皮质激素下调），也许 肾上腺对 ACTH 的高反应性和肥大也是如此。 为了阐明这一点，我们正在对 HPA 轴进行研究 重度抑郁症和单独匹配的对照。 促肾上腺皮质激素(1-24) 刺激被用来评估肾上腺的敏感性， 绵羊 CRH (oCRH) 刺激用于评估促肾上腺皮质激素 下调和肾上腺磁共振 (MR) 成像 用于尺寸确定。 激素测量包括血浆 促肾上腺皮质激素 (1-39)、促肾上腺皮质激素 (1-24)。皮质醇和 OCRH。 具有生物活性的 ACTH 将 也确定了。 不同青春期阶段的青少年重度抑郁症也正在被 研究以确定青春期早期发育的贡献 成年后 HPA 轴活动成为一种反应性抑郁症。 我们假设抑郁症患者的 HPA 轴过度活跃处于以下状态： 依赖，并且在治疗后，激素测量将恢复 以一致的方式恢复正常。 因此，所有患者都被追踪 通过他们的治疗，并且正在接受第二次研究 缓解并停药至少一个月。 本文提出的研究应该增加 HPA 轴的证据 多动症是一种协调的生理现象 增加中枢神经系统对 CRH 产生的刺激。 这将给予更多 推动中枢神经递质对 HPA 轴调节的研究 重度抑郁、压力状态和其他导致的状况下的活动 增加 HPA 轴活性。