HORMONE RHYTHMS--METABOLIC SIGNIFICANCE IN DEPRESSION

这是一份为期五年的修订续期申请，以继续我们的研究 重度抑郁症患者HPA轴功能亢进。我们的假设，基于我们的 和其他人的数据是，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(否 质的失调或缺陷)，如ACTH降低所反映的 对CRH治疗的反应(促肾上腺皮质激素下调)，也许 肾上腺对ACTH和肥大的高反应性。 为了阐明这一点，我们正在对HPA轴进行研究。 重度抑郁者和单独配对的对照组。ACTH(1-24) 刺激被用来评估肾上腺的敏感性， 绵羊促肾上腺皮质激素释放激素(OCRH)刺激被用来评估促肾上腺皮质激素 肾上腺的磁共振(MR)成像 被用来确定大小。激素测量包括血浆 ACTH(1-39)、ACTH(1-24)。皮质醇和OCRH。生物活性ACTH将是 决心也很大。 青春期不同阶段的青少年抑郁症患者也在 研究从青春期早期就确定发育的贡献 成年后的HPA轴活动是一种反应性抑郁症。 我们假设抑郁症的HPA轴多动是一种状态- 依赖，并在治疗后，激素措施将恢复 以始终如一的方式回归正常。因此，所有的患者都在被追踪 通过他们的治疗，并正在进行第二次研究时， 缓解并停药至少一个月。 这里提出的研究应该增加HPA轴的证据 多动是一种协调的生理现象，由以下因素引起 中枢神经系统对CRH产生的刺激增加。这将给我们带来更多 中枢神经递质对HPA轴调节作用的研究进展 严重抑郁、应激状态和其他条件导致的活动 与HPA轴活动增加有关。

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.