Treatment Prediction in Adolescent and Adult Depression

描述（由申请人提供）：虽然有越来越多的证据表明青少年和成人抑郁症的连续性，在临床表现和自然史方面具有相似性，但成熟的差异也得到了强调。具体而言，几项研究报告了抑郁症青少年的脑电图（EEG）睡眠变化，下丘脑-垂体-肾上腺（HPA）活动和抗抑郁药（AD）反应与成人相比的更大变化。该提案旨在了解这些发育差异的潜在机制，并制定一项策略，用于识别可能从AD治疗中获益的青少年和成人患者，特别是安非他酮治疗。 基于在我们实验室进行的初步研究的结果，这项调查提出了预测AD的反应，缓释安非他酮在抑郁症的青少年和成年人通过评估快速眼动（REM）睡眠和HPA活性反应单剂量安非他酮管理开始治疗前。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的临床治疗8周。除了检查对安非他酮激发的REM睡眠（和HPA）反应与对药物的临床反应之间的关联强度外，还将获得心理社会指标（特别是压力生活经历和社会支持），以评估其对AD反应的贡献，包括单独和与神经生物学指标组合。 安非他酮之所以被特别选择，是因为与其他AD化合物（特别是三环类药物和选择性5-羟色胺再摄取抑制剂）相比，它对REM睡眠的影响相对轻微。其他AD化合物诱导的强REM睡眠抑制可能掩盖个体间差异;由于“天花板效应”，与治疗反应相关的敏感性的固有差异可能丢失。 青少年抑郁症是一个主要的公共卫生问题，不仅涉及年轻人口，而且还涉及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有关，并且由于它标志着大部分成年人复发性情绪障碍的大门，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，并且由于初始治疗可能影响后续治疗依从性和临床过程，因此识别将（或不会）从AD药物治疗中获益的抑郁青年至关重要。这项研究的结果不仅有助于开发新的、更有效的AD药物和青少年治疗策略，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。

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.