HORMONE RHYTHMS--METABOLIC SIGNIFICANCE IN DEPRESSION

这是一个为期五年的修订更新申请，以继续我们的研究， 抑郁症患者HPA轴功能亢进 我们的假设是基于 和其他人的数据，这是一个中枢神经系统（CNS）驱动的HPA 多动，与轴本身的正常适应性生理（没有 质量失调或缺陷），如ACTH减少所反映的。 对CRH给药的反应（促肾上腺皮质激素下调）， 肾上腺对促肾上腺皮质激素的高反应性和肥大。 为了阐明这一点，我们正在对HPA轴进行调查， 重度抑郁症患者和单独匹配的对照组。 促肾上腺皮质激素（1-24） 刺激被用于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，以及肾上腺的磁共振（MR）成像 用于大小测定。 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。 生物活性ACTH将 也决心。 处于不同青春期阶段的青少年重度抑郁症患者也被 研究以确定青春期早期发育的贡献 通过成年对HPA轴活动的反应性抑郁症。 我们假设抑郁症的下丘脑-垂体-肾上腺轴过度活跃是状态- 依赖，并在治疗后，激素的措施将返回 以一种始终如一的方式恢复正常。 因此，所有患者都被跟踪 通过他们的治疗，并正在进行第二次研究时， 缓解并停止用药至少一个月。 本文提出的研究应增加证据表明，HPA轴 多动症是一种协调的生理现象， 增加CRH产生的CNS刺激。 这将使更多的 促进中枢神经递质对HPA轴调节的研究 活动在严重抑郁症，压力状态，和其他条件导致 HPA轴活动增加。

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.