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）：尽管越来越多的证据表明青少年和成人抑郁症具有连续性，并且临床表现和自然史相似，但成熟方面的差异也得到了强调。具体来说，几项研究报告称，与成人相比，抑郁青少年的脑电图 (EEG) 睡眠变化、下丘脑垂体肾上腺 (HPA) 活动和抗抑郁 (AD) 反应存在更大的差异。该提案旨在了解这些发育差异背后的机制，并制定一种策略，用于识别可能从一般 AD 治疗、特别是安非他酮治疗中受益的患者（包括青少年和成人）。 根据我们实验室进行的初步研究结果，本研究建议通过评估抑郁症青少年和成人对单剂量安非他酮给药前的快速眼动 (REM) 睡眠和 HPA 活动反应来预测抑郁症青少年和成人对缓释安非他酮的 AD 反应。开始治疗。完成睡眠和神经内分泌评估后，受试者将接受为期 8 周的缓释安非他酮临床治疗。除了检查 REM 睡眠（和 HPA）对安非他酮挑战的反应与对药物的临床反应之间的关联强度外，还将获得心理社会测量（特别是压力生活经历和社会支持），以评估它们对 AD 反应的贡献，既可以单独使用，也可以与神经生物学措施结合使用。 之所以特别选择安非他酮，是因为与其他 AD 化合物（特别是三环类药物和选择性血清素再摄取抑制剂）相比，它对快速眼动睡眠的影响相对微妙。其他 AD 化合物引起的快速眼动睡眠强烈抑制可能掩盖个体间的差异；由于“上限效应”，与治疗反应相关的敏感性的固有差异可能会消失。 青少年抑郁症是一个重大的公共卫生问题，不仅关系到年轻人，还关系到成年人的长期心理健康和社会功能。由于青少年抑郁症与严重的发病率和死亡率相关，而且它标志着大部分成年人复发性情绪障碍的途径，因此早期识别和有效治疗青少年抑郁症至关重要。由于 AD 药物对发育中的人类大脑的长期影响尚不清楚，而且初始治疗会影响随后的治疗依从性和临床过程，因此需要确定哪些抑郁青少年会（或不会）从 AD 药物治疗中受益。至关重要的。这项研究的结果不仅有助于为青少年开发新型、更有效的 AD 药物和治疗策略，而且还将增强我们对一些成年抑郁症患者 AD 反应不足的神经生物学的理解。