Treatment Prediction in Adolescent and Adult Depression

青少年和成人抑郁症的治疗预测

• 批准号: 6779382
• 负责人: UMA RAO
• 金额: $ 35.1万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-09 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6779382
• 关键词: REM sleep; adolescence (12-20); adult human (21+); antidepressants; bupropion; clinical research; clinical trials; depression; drug screening /evaluation; electrocardiography; electroencephalography; electrooculography; human subject; human therapy evaluation; hypothalamic pituitary adrenal axis; mental disorder chemotherapy; neurobiology; neuropharmacology; patient oriented research; pediatric pharmacology; pharmacokinetics; prognosis; psychological stressor; public health; social psychology; social support network

DESCRIPTION (provided by applicant): Although there is growing evidence for continuities in adolescent and adult depression, with similarities in clinical presentation and natural history, maturational differences also have been highlighted. Specifically, several studies reported greater variations in electroencephalographic (EEG) sleep changes, hypothalamicpituitary-adrenal (HPA) activity and antidepressant (AD) response in depressed adolescents compared with the findings in adults. This proposal aims to understand the mechanism(s) underlying these developmental differences and to develop a strategy for use in identifying those patients, both youngsters and adults, who might benefit from AD treatment in general, and from bupropion treatment in particular. Based on the results of preliminary studies conducted in our laboratory, this investigation proposes to predict AD response to sustained-release bupropion in depressed adolescents and adults by assessing rapid eye movement (REM) sleep and HPA activity responses to single-dose bupropion administration prior to initiating treatment. Following completion of the sleep and neuroendrocrine assessments, subjects will receive clinical treatment with sustained-release bupropion for 8 weeks. In addition to examining the strength of association between REM sleep (and HPA) response to the bupropion challenge and clinical response to the drug, psychosocial measures (specifically stressful life experiences and social support) will be obtained in order to assess their contribution to AD response, both singly and in combination with the neurobiological measures. Bupropion was selected specifically because of its relatively subtle effects on REM sleep compared with the other AD compounds (tricyclic agents and selective serotonin reuptake inhibitors, in particular). The robust REM sleep suppression induced by the other AD compounds might mask inter-individual variability; inherent differences in sensitivity that relate to treatment response could be lost due to a "ceiling effect". Adolescent depression is a major public health problem that not only relates to the younger population, but also for the long-term mental health and social functioning of adults. Because depression in youngsters is associated with serious morbidity and mortality, and since it marks the gateway into recurrent mood disorders in a large proportion of adults, the early identification and effective treatment of depression in youngsters is of utmost importance. Because the long-term effects of AD agents on the developing human brain are not known, and because initial treatment can influence subsequent treatment compliance and clinical course, the identification of depressed youth who would (or would not) benefit from treatment with AD drugs is crucial. Results of the proposed study should not only be helpful in developing novel and more effective AD drugs and treatment strategies for youngsters, but also will enhance our understanding of the neurobiology of inadequate AD response in some adult patients with depression.

描述（由申请人提供）：尽管有越来越多的青少年和成人抑郁症连续性的证据，但在临床表现和自然历史方面具有相似性，但也强调了成熟差异。具体而言，几项研究报告了与成年人的发现相比，抑郁症的青少年的脑电图（EEG）睡眠变化，下丘脑 - 粘膜 - 肾上腺肾上腺（HPA）活性和抗抑郁（AD）反应的变化更大。该提案旨在了解这些发育差异的基础机制，并制定一种用于识别这些患者（包括年轻人和成年人）的策略，这些患者一般可以从AD治疗中受益，尤其是在安非他酮治疗中受益。 基于我们实验室中进行的初步研究的结果，这项研究建议通过评估抑郁症的青少年和成年人对持续释放的安非他酮的反应，通过评估快速眼动运动（REM）睡眠（REM）睡眠和HPA活性对单剂量bupropropion施用的反应。在完成睡眠和神经内分泌评估后，受试者将接受持续释放安非他酮8周的临床治疗。除了检查REM睡眠（和HPA）对安非他酮挑战的反应和对药物的临床反应之间的关联强度外，还将获得社会心理措施（特别是压力性的生活经验和社会支持），以评估其对AD反应的贡献，无论是单独且与神经生物学测量的贡献。 与其他AD化合物（尤其是三环剂和选择性5-羟色胺再摄取抑制剂，特别是对REM睡眠的影响相比），因此选择了安非他酮。其他AD化合物诱导的强大REM抑制可能会掩盖个体间的变异性；与治疗反应有关的敏感性固有差异可能会因“天花板效应”而丢失。 青春期抑郁症是一个主要的公共卫生问题，不仅与年轻人的人口有关，而且与成年人的长期心理健康和社会功能有关。由于年轻人的抑郁症与严重的发病率和死亡率有关，并且由于大部分成年人的反复情绪障碍的门户标志着，因此早期鉴定和有效治疗年轻人的抑郁症是至关重要的。由于广告药物对发展中人脑的长期影响尚不清楚，并且初始治疗会影响随后的治疗依从性和临床过程，因此鉴定抑郁症的年轻人（或不会）从AD药物治疗中受益至关重要。拟议的研究的结果不仅应有助于制定新颖，更有效的AD药物和年轻人的治疗策略，而且还将增强我们对一些成年抑郁症患者的AD反应不足的神经生物学的理解。