Personality Development and Vulnerability to First-Episode Depression

描述（由申请人提供）：重度抑郁症（MDD）是一种常见病，通常具有慢性或复发性病程。预防被认为是减轻这种疾病负担的关键。然而，一个有效的预防计划需要彻底了解诱发因素和它们传递风险的机制。人格特征是重度抑郁症发病的有力预测因素，但目前尚不清楚哪些特征是脆弱的最佳标志。此外，这些联系背后的机制还没有得到很好的理解。本项目旨在确定抑郁症发生的主要人格危险因素，并阐明相关的病因过程，包括与生活压力的相互作用以及神经和内分泌机制。另一个目标是了解伴随抑郁症在多大程度上扭曲了人格测试的分数，从而为基础人格研究和临床评估提供信息。我们建议招募575名从未经历过重度抑郁发作的14岁和15岁女性（发生率最高的人口阶层）。参与者将进行三次亲自评估：基线、第18个月和第36个月。他们将完成一项全面的诊断性访谈，一系列人格量表，以及负面生活事件、日常功能、皮质醇水平和大脑活动的测量。他们还将在评估之间参加简短的电话访谈，以尽量减少在回忆抑郁发作和压力生活事件时的偏见。家庭精神病史和告密者的性格评分将从父母那里获得。我们将使用结构方程模型（SEM）来高精度地估计性状得分，并使用生长模型来消除伴随抑郁引起的这些评分中的扭曲。我们期望这些分析策略能够大大提高我们的分析能力，并将在未来的研究中开发出修正人格分数的公式。接下来，我们将研究人格和环境在重度抑郁症易感性发展中的动态相互作用。我们还将测试两种有希望的病理发育轨迹的生物标志物。此外，我们将开发一种人格筛选，在青少年经历抑郁症之前识别出他们的风险。这个多学科项目将形成一个研究项目的基础，最终寻求设计和针对青少年抑郁症的新的预防干预措施。

DESCRIPTION (provided by applicant): Major depressive disorder (MDD) is a common illness that often has chronic or recurring course. Prevention is believed to be the key to reducing the burden of this disorder. However, an effective prevention program requires thorough knowledge of predisposing factors and mechanisms by which they convey risk. Personality characteristics are powerful predictors of MDD onset, but it is not yet clear which traits are the best markers of vulnerability. Also, the mechanisms underlying these links are not well understood. This project aims to identify main personality risk factors for depression onset and elucidate relevant etiologic processes, including interactions with life stress as well as neural and endocrinal mechanisms. Another objective is to learn how much concomitant depression distorts scores on personality measures, thus informing basic personality research and clinical assessment. We propose to recruit 575 14- and 15-year-old females (demographic stratum at highest risk for incident depression) who have never experienced a major depressive episode. Participants will be assessed in person three times: at baseline, month 18, and month 36. They will complete a thorough diagnostic interview, a battery of personality scales, as well as measures of negative life events, daily functioning, cortisol levels, and brain activity. They also will participate in brief phone interviews between assessments to minimize biases in recall of depressive episodes and stressful life events. Family psychiatric history and informant-ratings of personality will be obtained from a parent. We will use Structural Equation Modeling (SEM) to estimate trait scores with high precision, and growth modeling to remove distortions in these ratings induced by concomitant depression. We expect these analytic strategies to substantially enhance power of our analyses and will develop formulas for correcting personality scores in future studies. Next, we will examine the dynamic interplay between personality and environment in development of vulnerability to MDD. We also will test two promising biomarkers of pathological developmental trajectories. Furthermore, we will develop a personality screen to identify adolescents at risk well before they experienced depression. This multidisciplinary project will form the basis for a program of research that ultimately seeks to design and target new preventive interventions for adolescent depression.