THYROID AXIS IN MAJOR DEPRESSION

甲状腺轴严重抑制

• 批准号: 6351714
• 负责人: PHILIP T NINAN
• 金额: $ 22.89万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6351714
• 关键词: autoantibody; clinical research; electrocardiography; hormone therapy; human subject; human therapy evaluation; hypothalamic pituitary axis; immunologic assay /test; iodide peroxidase; major depression; mental disorder chemotherapy; mental disorder diagnosis; placebos; sertraline; thyroglobulin; thyroid function; thyroid gland; thyrotropin; thyrotropin releasing hormone; triiodothyronine

The goals of this proposal are to examine the relationship between Major Depressive Disorder (MDD) and abnormalities of the hypothalamic pituitary thyroid (HPT) axis. HPT abnormalities, specially subclinical hypothyroidism, are present in a significant number of patients with MDD. Yet the most common HPT abnormality reported in MDD is a blunted TSH response to TRH challenge suggesting central hyperactivity of the HPT axis. Perturbation of the normal functioning of the HPT axis is postulated to reflect central abnormality of TRH secretion which contribute to the heterogeneity of MDD, and plays a role in the response to antidepressant treatment. This application proposes to systematically examine the value of supplemental triiodothyronine (T3, Cytomel) with sertraline, a selective serotonin reuptake inhibitor (SSRI) in the treatment of MDD. The focus will be on two overlapping populations: 1) those with evidence of HPT abnormalities, and 2) those who did not respond to a previous adequate SSRI trial. This application proposes to programmatically develop a large study population of patients with MDD, classified with respect to HPT abnormalities and previous response to antidepressant treatment. The HPT axis will be systematically assessed in 200 patients with MDD and the benefit of triiodothyronine or placebo supplementation of sertraline examined. Half the study patients will have documented failure to a previous SSRI trial. The assessment of the HPT axis will include repeated peripheral baseline measures of TSH, total and free T3 and T4, antibodies to thyroglobulin and thyroid peroxidase; and the TRH stimulation test. Assessments will be repeated again after treatment. The primary hypothesis is that triiodothyronine supplementation sertraline will result in a greater improvement in HAM-D scores compared to placebo. Additional hypotheses will examine the role of HPT abnormalities and previous treatment response in the improvement to concomitant triiodothyronine with sertraline. This proposal is designed to provide a definitive clinical study of triiodothyronine augmentation of SSRI. It has the potential to significantly alter clinical practice in the management of MDD, particularly in patients who are non-responsive to antidepressants. The proposal will shed light on the role of the HPT axis in the pathophysiology and heterogeneity of MDD.

该提案的目标是检查主要之间的关系 抑郁症 (MDD) 和下丘脑异常 垂体甲状腺（HPT）轴。 HPT 异常，特别是亚临床异常 甲状腺功能减退症，存在于相当多的患者中 医学博士。 然而，MDD 中最常见的 HPT 异常是迟钝的 TSH 对 TRH 挑战的反应表明中枢机能亢进 HPT 轴。 HPT 轴正常功能的扰动是 推测反映 TRH 分泌的中枢异常 有助于 MDD 的异质性，并在响应中发挥作用 到抗抑郁治疗。 本申请建议 系统地检查补充三碘甲状腺原氨酸（T3、 Cytomel）与舍曲林（一种选择性血清素再摄取抑制剂） （SSRI）治疗MDD。 重点将放在两个重叠的地方 人群：1) 有 HPT 异常证据的人群，以及 2) 对先前充分的 SSRI 试验没有反应的人。 该应用程序建议以编程方式开发一项大型研究 MDD 患者群体，根据 HPT 进行分类 异常和先前对抗抑郁治疗的反应。 这 将对 200 名 MDD 患者进行系统性评估 HPT 轴 三碘甲状腺原氨酸或安慰剂补充舍曲林的益处 检查了。 一半的研究患者将有记录失败 之前的 SSRI 试验。 HPT 轴的评估将包括 重复外周基线 TSH、总 T3 和游离 T4 测量， 甲状腺球蛋白和甲状腺过氧化物酶抗体；和TRH 刺激测试。 治疗后将再次重复评估。 主要假设是补充三碘甲状腺原氨酸 舍曲林将导致 HAM-D 分数比 安慰剂。 其他假设将检验 HPT 的作用 异常情况和既往治疗反应的改善 三碘甲状腺原氨酸与舍曲林合用。 该提案旨在提供明确的临床研究 SSRI 的三碘甲状腺原氨酸增强作用。它有潜力 显着改变 MDD 管理的临床实践， 特别是对于抗抑郁药无反应的患者。 这 该提案将阐明 HPT 轴在 MDD 的病理生理学和异质性。