Validation of Preschool Depressive Syndrome

描述（由申请人提供）：大量的发展研究已经发现了处于抑郁高风险的婴幼儿的早期行为和生物学变化。尽管有这些非常有启发性的发现，在研究者的初步研究之前，没有足够的数据来解决6岁以下的儿童是否会表现出临床显著的抑郁症的问题。已知的慢性和复发过程，以及6岁后发现的相对治疗抵抗，强调了在最早的发展点识别抑郁症的必要性。研究者和他的同事正在完成一项由联邦政府资助的关于学龄前抑郁症分类学的研究。本研究的发现首次证明，当根据年龄调整后的症状表现对评估进行修改时，使用DSM-IV MDD标准可以在学龄前儿童中识别出有效的抑郁综合征。该综合征的初步验证已经建立在与许多标志物的关联基础上，包括特定和稳定的症状群，相关疾病的家族史增加，与对照组相比显著的抑郁严重程度和社交障碍。研究结果提出了关于临床抑郁症发作的持续时间以及区分综合征和亚综合征状态的标准的问题。本申请建议利用从本研究中得出的敏感和特定的标准来确定基于社区的抑郁学龄前儿童样本（和适当的对照），进行实地试验和纵向随访。为了解决初步研究中提出的问题，本研究建议在评估多个领域的损害的基础上，使用一种新的综合和适合年龄的诊断方法来定义学龄前抑郁症的临床特征。在全国范围内，给这些幼儿开的未经核准的抗抑郁药处方惊人地增加，这代表着一场严重的公共卫生危机，因此，验证学龄前抑郁症诊断标准的必要性更加突出。虽然没有数据支持的治疗是一种明显的危险，但早期干预抑郁症的可能性是一种令人信服的可能性，必须积极探索。有效的诊断标准对于这些未来的治疗研究和促进这种疾病的发育神经生物学研究是必要的。

DESCRIPTION (provided by applicant): Numerous developmental studies have detected very early behavioral and biological changes in infants and toddlers at high-risk for depression. Despite these highly suggestive findings, prior to the investigator's preliminary study, there was insufficient data to address the question of whether children younger than six could manifest clinically significant depression. The need to identify depression at the earliest developmental point is underscored by the known chronic and relapsing course, and relative treatment resistance of the disorder when identified after six years of age. The investigator and colleagues are completing a federally funded study of the nosology of preschool depression. Findings from this study are the first to demonstrate that a valid depressive syndrome can be identified in preschool children using DSM-IV MDD criteria when the assessment is modified for age adjusted symptom manifestations. Preliminary validation of this syndrome has been established based on the association with numerous markers including a specific and stable symptom constellation, increased family history of related disorders, significant depression severity compared to controls and social impairment. Study findings raised questions about the duration of an episode of clinical depression and the criteria that distinguish syndromal from sub-syndromal states. This application proposes to utilize the sensitive and specific criteria derived from this study to ascertain a community based sample of depressed preschoolers (and appropriate controls) for a field trial and longitudinal follow-up. To address questions raised by the preliminary study, this investigation proposes to define the clinical characteristics of preschool depression using a new comprehensive and age appropriate diagnostic measure, in addition to assessing impairment in multiple domains. The need to validate diagnostic criteria for preschool depression is heightened by the alarming national increase in the off-label prescription of antidepressants to these young children, representing a serious public health crisis. While treatment unsupported by data is an obvious danger, the potential for earlier intervention in depression is a compelling possibility that must be aggressively explored. Valid diagnostic criteria are necessary for these future treatment studies and to facilitate investigations of the developmental neurobiology of this disorder.