Depression, Stress, and Down Syndrome. A Multimethod Approach to Assessment

项目摘要 患有唐氏综合症(DS)和其他智力和发育障碍(IDD)的人在 与普通人群相比，有压力的生活经历和抑郁的风险更大，但可能性更小 确诊并接受适当的治疗。这一群体缺乏经过验证的评估工具是一种 主要障碍是研究、诊断和治疗DS患者的抑郁症。最重要的是 这份K08提案的目的是为作为临床心理学家的候选人提供培训， 心理测量学和基因组研究相结合所需的指导和研究机会 在评估具有挑战性的人群中研究压力和抑郁的生物标记物的方法 支持候选人的长期目标，即进行联邦资助的基因信息测量 对患有DS和其他形式的IDD的人进行研究。候选人和指导团队已经创建了一个 全面的培训计划，包括课程作业、强化指导、暑期计划和会议 DS相关的发育和精神表型、统计学和表观遗传生物标记物。这个 多学科指导团队由领先的专家组成：Colleen Jackson-Cook博士(临床 细胞遗传学家和医学遗传学家；主要导师)，DS的表观遗传学和细胞遗传学的领先专家； 阿南达·阿姆施塔特博士(临床心理学家；共同导师)，压力和抑郁专家；乔治博士 卡彭(共同导师)，DS发育表型专家。导师团队由Dr。 阿卡多博士，董事会认证的发育儿科医生，具有发育障碍方面的专业知识。 他们提供表型测量、统计遗传学和生物信息学方面的专业知识。 应聘者将通过进行多阶段、多方法的测量研究来应用所获得的技能 精神障碍患者的应激性生活事件和抑郁。第一阶段将包括预赛 75例样本中自我报告、照顾者报告和临床诊断数据的心理测量学分析 患有马赛克障碍(MDS)的参与者，他们较高的认知和语言功能可以为 精神障碍患者的社会和情感体验。此数据将用于测量细化 在第二阶段进行部署，在该阶段中将在 100名患有完整(非马赛克)D的参与者的样本。第三个阶段将包括比较 诊断为抑郁症的完全性DS患者的全基因组甲基化和端粒长度 (病例；n=25)和没有(对照；n=25)，以确定潜在的抑郁症生物标志物。此外，这个角色 紧张性生活事件将在抑郁症的生物学嵌入中进行探索。这些人的身份 生物标记物不仅将补充患者报告的评估工具的有效性，它们还可能 作为经济高效的诊断工具，并在鉴别诊断和未来发挥着至关重要的作用 这一人群中抑郁症的药物和心理社会治疗研究。

Project Summary People with Down syndrome (Ds), and other intellectual and developmental disabilities (IDD), are at greater risk for stressful life experiences and depression than the general population, yet are less likely to be diagnosed and receive appropriate treatment. The lack of validated assessment tools for this population is a major impediment to research, diagnosis, and treatment of depression for people with Ds. The overarching goal of this K08 proposal is to provide the candidate, who is a clinical psychologist, with the training, mentorship, and research opportunities necessary to combine psychometric and genomic research methodologies to study biomarkers of stress and depression in populations that are challenging to assess, thus supporting the candidate's long-term goal of conducting federally-funded genomically-informed measurement research in people with Ds and other forms of IDD. The candidate and mentorship team have created a comprehensive training plan including coursework, intensive mentoring, summer programs, and conferences in Ds-related developmental and psychiatric phenotypes, statistics, and epigenetic biomarkers. The multidisciplinary mentorship team is comprised of leading experts: Dr. Colleen Jackson-Cook (clinical cytogeneticist and medical geneticist; primary mentor), a leading expert in epigenetics and cytogenetics of Ds; Dr. Ananda Amstadter (clinical psychologist; co-mentor), an expert in stress and depression; and Dr. George Capone (co-mentor), an expert in Ds developmental phenotypes. The mentorship team is rounded out by Dr. Accardo, board certified developmental pediatrician with expertise in developmental disabilities, and Drs. Aggen, and York, who provide expertise in phenotype measurement, statistical genetics, and bioinformatics. The candidate will apply the acquired skills by conducting a multistage, multi-method measurement study of stressful life events and depression in people with Ds. The first stage will involve the preliminary psychometric analyses of self-report, caregiver-report, and clinical diagnostic data from a sample of 75 participants with mosaic Ds (mDs), whose higher cognitive and verbal functioning can provide a “window” into the social and emotional experiences of people with Ds. This data will be used for measure refinement for deployment in the second stage in which the refined assessments will be administered and validated within a sample of 100 participants with complete (non-mosaic) Ds. The third stage will involve a comparison of genome-wide methylation and telomere length in participants with complete Ds diagnosed with depression (cases; n=25) and without (controls; n=25) to identify potential biomarkers of depression. Furthermore, the role of stressful life events will be explored in the biological embedding of depression. The identification of these biomarkers will not only complement the validation of patient-reported assessment tools, they may also serve as cost-effective diagnostic tools in their own right and play a vital role in differential diagnosis and future research on pharmacological and psychosocial treatments for depression in this population.