METABOLIC ASPECTS OF BODY WEIGHT CHANGE IN DEPRESSION

抑郁症中体重变化的代谢方面

• 批准号: 3380367
• 负责人: MADELYN H FERNSTROM
• 金额: $ 10.63万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1992-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3380367
• 关键词: antidepressants; bioenergetics; body temperature; body weight; caloric dietary content; desipramine; drug adverse effect; human subject; laboratory rat; major depression; metabolism; nutrition related tag; oximes; oxygen consumption; radioimmunoassay

Antidepressant treatment is reputed to be associated with unwanted, excessive weight gain. Regulation of body weight is a complex problem and can result from increase caloric intake, decreased caloric expenditure, or both. In this proposal, based on preliminary findings, the major focus in primarily on caloric expenditure, however selected studies also address food preference and caloric intake. The working hypothesis is that antidepressant-induced weight gain in humans follow from a reduction in caloric expenditure. The proposed studies will dissect the effects of antidepressant drugs on metabolism and metabolic rate. Studies will be performed in depressed humans and in rats. In depressed inpatients hospitalized for 4 weeks, the effects of two antidepressants (desipramine and fluvoxamine) on metabolic rate will be compared. Data will also be obtained on caloric intake in treated subjects. The results should expose which drug type(s) induce a decline in metabolic rate and/or influence body weight. Studies in depressed outpatients will explore for metabolic changes in subjects treated for 4 or more months with imipramine. These studies will characterize the time-course of metabolic effects, and determine if reductions in metabolic rate observed after 2-4 weeks of treatment are sustained over longer periods. Finally, experiments will be pursued in rats to elucidate the mechanism(s) by which drug- induced changes in metabolism occur. In both humans and rats, the actual experiments involve measurements of metabolic rate by quantitation of oxygen inspiration and carbon dioxide expiration. Measurements in blood of key energy substrates and insulin will also be made, by chemical and radioimmunoassay techniques. These latter determinations will be an important complement to the metabolic rate determinations made using inspired and expired gases. Overall, the results of these studied should help to determine that portion of the depressed population susceptible to antidepressant-induced weight gain, and the pharmacologic and metabolic causes of their increase in body weight. The findings may therefore be useful in formulating a pharmacologic strategy that will avoid weight gain as a side- effect to antidepressant treatment.

抗抑郁药物的治疗被认为与 不想要的，过度的体重增加。调节体重是一种 这是一个复杂的问题，可能是由于增加卡路里摄入量所致， 减少卡路里消耗，或者两者兼而有之。在本提案中，基于 初步发现，主要关注的是卡路里 支出，然而，选定的研究也涉及食品 喜好和卡路里摄入量。工作假说是 抗抑郁药物引起的人类体重增加源于 减少卡路里消耗。拟议的研究将 剖析抗抑郁药物对新陈代谢的影响 代谢率。研究将在抑郁症患者身上进行。 在老鼠身上也是如此。在住院4周的抑郁症患者中， 地塞帕明和氟伏沙明对抑郁症患者的影响 代谢率将被比较。数据也将在以下地址获得 受试者的卡路里摄入量。结果应该会暴露出来 哪种药物类型(S)会导致代谢率和/或 影响体重。对抑郁症门诊患者的研究将 探讨接受4次或4次以上治疗的受试者的代谢变化 服用丙咪嗪几个月。这些研究将描述 代谢影响的时间进程，并确定是否减少 治疗2-4周后观察到的代谢率为 在更长的时期内持续。最后，实验将是 在大鼠身上进行追踪，以阐明药物- 新陈代谢会发生诱导性变化。在人类和老鼠身上， 实际的实验包括代谢率的测量。 通过氧气吸入和二氧化碳的定量 过期了。血液中关键能量底物和 还将通过化学和放射免疫分析来制造胰岛素。 技巧。这些后一种决定将是一个重要的 对代谢率测定的补充 吸入和呼出的气体。总体而言，这些研究的结果 应该有助于确定萧条人口中的那部分人 易受抗抑郁剂引起的体重增加的影响， 它们在体内增加的药理和代谢原因 重量。因此，这些发现可能有助于制定一种 避免体重增加的药物策略- 对抗抑郁药物治疗的影响。