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Novel Associations of Anxiety, Depression and Telomeres across Mid- and Late-Life

中年和晚年焦虑、抑郁和端粒的新关联

基本信息

批准号：
9039154
负责人：
Olivia Ifeoma Okereke
金额：
$ 40.23万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-04-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9039154
关键词：
Address Age Aging Antidepressive Agents Anxiety Basic Science Biological Aging Biological Assay Biological Markers Blood Body mass index Cardiovascular Diseases Chronic Clinical Clinical Research Cohort Studies Collection Communities Comorbidity Data Data Quality Development Diabetes Mellitus Diagnosis Disease Disease Outcome Elderly Elements Exercise Female Fright Future Health Heart Diseases Hormone use Human Hypertension Impairment Incidence Individual Length Life Longevity Malignant Neoplasms Measures Mediating Mediation Medical Mental Depression Mental Health Mental Health Associations Mental disorders Modeling Moods Morbidity - disease rate National Institute of Mental Health Nurses&apos Health Study Outcome Oxidative Stress Participant Pathway interactions Patient Self-Report Pharmaceutical Preparations Phase Phobic anxiety Physicians Predictive Value Psychiatric therapeutic procedure Public Health Quality of life Questionnaires Registered nurse Resources Rewards Risk Risk Factors Role Sampling Scientist Smoking Telomere Shortening Testing Translations Update Validation Vascular Diseases Woman Work anxiety symptoms burden of illness clinically significant cohort cost depressive symptoms disorder risk follow-up functional disability health data high risk improved innovation late-life anxiety lifestyle factors middle age mood symptom novel psychological distress telomere

项目摘要

DESCRIPTION (provided by applicant): Anxiety and depression are both associated with substantial functional and quality of life impairment in older adults, and are related to development of major morbidities over- represented in aging, such as cardiovascular disease and cancer. Indeed, chronic mental disorders are now hypothesized to represent a model for accelerated aging via telomere shortening under conditions of high oxidative stress. Intriguingly, recent basic science evidence has demonstrated that high loading of oxidative stress may induce abnormal mood symptoms, such as anxiety and fear. However, implications of this work, the possibility that higher cumulative oxidative stress and accelerated biological aging may predispose individuals to later- life anxiety or depression - remain relatively unexplored in humans. Thus, a lifespan-oriented approach to addressing mood and telomere lengths provides an ideal strategy, and this project aims to identify and characterize potential reciprocal associations of phobic anxiety and depression with telomere length. By leveraging existing data, as well as collecting new data on telomere lengths and mental health outcomes, from a long-standing, large cohort study of female participants (the Nurses' Health Study), we plan to examine prospectively the relations of: 1) mid-life anxiety and depression to telomere length change over 10 years; 2) mid-life telomere length to development of later-life anxiety and depression. Further, by exploring mediation by medical conditions, such as vascular diseases and risk factors, we can elucidate pathways - addressing whether any identified telomere-mental health associations are explained, in part, by medical comorbidity. In summary, this study will conduct hypothesis testing of an innovative clinical translational model in which telomere shortening not only may be a consequence of psychological distress but also may be assessed at earlier life windows to predict later-life anxiety and depression. In addition, study aims will be achieved with enormous cost- and resource-efficiency. Findings could enrich biologic understanding of late-life anxiety and depression, informing new pathways involving telomeres, along with the possibility of novel future treatments addressing such pathways.

描述（由申请人提供）：焦虑和抑郁均与老年人的实质性功能和生活质量受损相关，并与衰老中过度表现的主要疾病（如心血管疾病和癌症）的发生相关。事实上，慢性精神障碍现在被假设为在高氧化应激条件下通过端粒缩短加速衰老的模型。有趣的是，最近的基础科学证据表明，高负荷的氧化应激可能会引起异常的情绪症状，如焦虑和恐惧。然而，这项工作的影响，更高的累积氧化应激和加速生物衰老可能使个体更容易患上晚年焦虑或抑郁症的可能性，在人类中仍然相对未被探索。因此，以寿命为导向的方法来解决情绪和端粒长度提供了一个理想的策略，该项目的目的是确定和表征潜在的相互关联的恐惧性焦虑和抑郁症与端粒长度。通过利用现有数据，以及收集关于端粒长度和心理健康结果的新数据，从一项长期的女性参与者大型队列研究（护士健康研究）中，我们计划前瞻性地研究：1）中年焦虑和抑郁与端粒长度变化的关系超过10年; 2）中年端粒长度与晚年焦虑和抑郁的发展。此外，通过探索医疗条件（如血管疾病和风险因素）的中介作用，我们可以阐明途径-解决任何已确定的端粒-心理健康关联是否部分由医疗合并症解释。总之，本研究将对一种创新的临床转化模型进行假设检验，在该模型中，端粒缩短不仅可能是心理困扰的结果，而且可能在早期生活窗口进行评估，以预测晚年的焦虑和抑郁。此外，研究目标将以巨大的成本和资源效率实现。这些发现可以丰富对晚年焦虑和抑郁的生物学理解，为涉及端粒的新途径提供信息，沿着新的未来治疗方法可能解决这些途径。