Treatment Prediction in Adolescent and Adult Depression

尽管有越来越多的证据表明青少年和成年人的抑郁症持续存在，但在 临床表现和自然病史、成熟期的差异也被强调。具体来说， 几项研究报告了脑电(EEG)睡眠变化的更大差异，下丘脑- 抑郁症青少年脑下垂体-肾上腺皮质(HPA)活性和抗抑郁药(AD)反应的比较 在成年人身上的研究结果。这一建议旨在了解这些发展背后的机制(S) 差异，并制定一种策略，用于识别哪些患者，包括青少年和成年人， 可能从AD治疗中受益，尤其是安非他酮治疗。 根据我们实验室进行的初步研究结果，这项调查建议预测 快眼评估对抑郁青少年和成人安非他酮缓释片的AD反应 运动(REM)睡眠和HPA活动对开始前单剂量安非他酮的反应 治疗。在完成睡眠和神经内分泌评估后，受试者将接受临床 安非他酮缓释片治疗8周。除了考察联合的力量之外 在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， 将获得心理社会措施(特别是有压力的生活经历和社会支持)，以便 评估他们对AD反应的贡献，包括单独和结合神经生物学措施。 之所以特别选择安非他酮，是因为与安非他明相比，安非他酮对快速眼动睡眠的影响相对较小 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)。健壮的 其他AD化合物引起的快速眼动睡眠抑制可能掩盖了个体间的变异性；固有的 由于“天花板效应”，与治疗反应有关的敏感性差异可能会消失。 青少年抑郁症是一个主要的公共卫生问题，不仅与年轻人口有关，而且 也是为了成年人的长期心理健康和社会功能。因为青少年中的抑郁症是 与严重的发病率和死亡率有关，因为它标志着进入复发情绪的大门 在很大比例的成年人精神障碍中，抑郁症的早期识别和有效治疗 年轻人是最重要的。因为AD药物对发育中的人类的长期影响 大脑是未知的，因为最初的治疗会影响随后的治疗依从性 临床病程，确定将(或不会)从AD治疗中受益的抑郁青年 毒品是至关重要的。拟议的研究结果不仅应该有助于开发新的和更多的 有效的青少年AD药物和治疗策略，也将增进我们对AD的了解 部分成年抑郁症患者AD反应不足的神经生物学研究。

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, hypothalamic- pituitary-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 specifcally 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.