Validation of Preschool Depressive Syndrome

描述(由申请人提供)：许多发育研究发现，患有抑郁症的婴儿和蹒跚学步的儿童早期的行为和生物变化。尽管有这些极具启发性的发现，但在研究人员进行初步研究之前，还没有足够的数据来解决六岁以下儿童是否会表现出临床上显著的抑郁症的问题。已知的慢性和复发病程，以及在六岁后发现抑郁症时的相对治疗抵抗，突显了在最早发育点识别抑郁症的必要性。这位研究人员和他的同事正在完成一项由联邦政府资助的学龄前抑郁症病因学研究。这项研究的发现首次证明，当评估针对年龄调整的症状表现进行修改时，可以使用DSM-IV MDD标准在学龄前儿童中识别有效的抑郁综合征。这种综合征的初步验证是基于与许多标记物的关联，包括特定和稳定的症状星座、相关疾病家族史的增加、与对照组相比显著的抑郁严重程度和社会损害。研究结果对临床抑郁症发作的持续时间以及区分症状和亚症状状态的标准提出了质疑。这项应用建议利用这项研究得出的敏感和特定的标准来确定社区为基础的抑郁学龄前儿童样本(和适当的对照)，用于现场试验和纵向跟踪。为了解决初步研究提出的问题，这项调查建议除了评估多个领域的损害外，还应使用一种新的全面的、与年龄相适应的诊断方法来确定学龄前抑郁症的临床特征。全国范围内给这些幼儿开出的抗抑郁药处方令人震惊地增加，这意味着严重的公共卫生危机，这加剧了验证学龄前抑郁症诊断标准的必要性。虽然没有数据支持的治疗是一个明显的危险，但对抑郁症进行早期干预的可能性是一个令人信服的可能性，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对这种疾病的发育神经生物学的研究是必要的。

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.