SEROTENERGIC MECHANISMS IN SLEEP AND DEPRESSION

睡眠和抑郁中的血清素机制

• 批准号: 2890952
• 负责人: JOHN C GILLIN
• 金额: $ 23.98万
• 依托单位: VETERANS MEDICAL RESEARCH FDN/SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-30 至 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2890952
• 关键词: REM sleep; aminoacid metabolism; bupropion; chronotherapy; clinical research; diet therapy; dietary aminoacid; emotions; human subject; human therapy evaluation; longitudinal human study; major depression; neuroendocrine system; neuropharmacology; neurotransmitter metabolism; nutrition related tag; pharmacokinetics; serotonin; serotonin inhibitor; sertraline; tryptophan

DESCRIPTION (Adapted from applicant's abstract): The proposed studies will attempt to investigate the effects of serotonin depletion on mood, nocturnal polygraphic sleep measures, and neuroendocrine secretion in (a) normal volunteer, (b) patients with Major Depressive Disorder before and during double-blind antidepressant treatment with either sertraline or bupropion, and (c) nonaffected individuals who are at high genetic risk for the development of a mood disorder. The investigator will experimentally induce serotonin depletion with the tryptophan-free amino acid drink (TFD), which has been reported to reduce brain serotonin or its metabolites in animals and humans and to briefly reverse the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) in euthymic patients. Based upon his pilot data, the investigator hopes to refine the current methodology with (a) the development of a new control drink which contains tryptophan but does not alter plasma tryptophan levels and (b) a lower dose of amino acids in the TFD which avoid side effects, such as nausea and vomiting in women, but still significantly and substantially reduces plasma tryptophan concentrations. We predict that the TFD, compared with the control drink, will significantly induce depressive symptoms in sertraline-but not bupropion-treated euthymic patients, but only at about 4-6 weeks rather than 4-6 months of treatment. In addition, he predicts that the TFD will reverse the rapid eye movement (REM) sleep suppressing effects of sertraline at both time points. He predicts that morning administration of TFD will increase midafternoon mean secretion of cortisol and prolactin 5-7 hours later in normal controls and depressed patients, with a greater increase in depressed patients. Finally, he hopes to extend and confirm the hypothesis that the TFD induces depressogenic symptoms and signs (greater shortening of REM latency, increased REM percentage and REM Density, and cortisol and prolactin secretion in unaffected individuals from family positive than from family negative homes.

描述（根据申请人的摘要改编）：拟议的研究 将尝试研究5-羟色胺耗竭对情绪的影响， 夜间聚会睡眠措施和神经内分泌分泌 （a）正常志愿者，（b）患有重度抑郁症的患者 在双盲抗抑郁药治疗期间，两种舍曲林 或安非他酮，以及（c）未受影响的人 有情绪障碍发展的风险。调查员会 实验诱导无色氨基的5-羟色胺耗竭 酸性饮料（TFD），据报道降低脑5-羟色胺或 它在动物和人类中的代谢产物，并短暂扭转 选择性5-羟色胺再摄取抑制剂的抗抑郁作用 （SSRIS）在正式患者中。根据他的飞行员数据 研究人员希望通过（a）完善当前的方法 开发包含色氨酸但不包含色氨酸的新控制饮料 改变血浆色氨酸水平和（b）较低剂量的氨基酸 避免副作用的TFD，例如女性恶心和呕吐，但 仍然显着并大大减少血浆色氨酸 浓度。我们预测TFD与对照相比 饮料，将大大引起舍曲林但抑郁症状 不是安非他酮治疗的格特符号患者，但仅在大约4-6周内 而不是4-6个月的治疗。此外，他预测 TFD将逆转快速眼动（REM）睡眠抑制效果 两个时间点的舍曲林。他预测那天早上 TFD的管理将增加中午的平均分泌 5-7小时后，皮质醇和催乳素在正常对照中和抑郁症 患者，抑郁症患者的增加。最后，他 希望扩展并确认TFD引起的假设 降低症状和体征（更大的REM潜伏期缩短， REM百分比和REM密度增加，皮质醇和催乳素 来自家庭积极的不受影响的人的分泌比 家庭负面的房屋。