Depression, Stress, Aging & Proinflammatory Cytokines

抑郁、压力、衰老

基本信息

批准号：
7847756
负责人：
JANICE KIECOLT-GLASER
金额：
$ 0.98万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-15 至 2009-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7847756
关键词：
Address Age Aging Alleles Alzheimer&apos s Disease Antigens Anxiety Anxiety Disorders Behavioral C-reactive protein Caregivers Caring Chronic Chronic stress Coronary Data Dementia Depressive disorder Development Disease Distress Elderly Event Exhibits Family Gene Frequency Genes Genetic Genetic Polymorphism Genetic Predisposition to Disease Genetic Variation Genotype Health Heart Husband Hypertension IL6 gene Immune Immune response Immune system Incidence Individual Inflammatory Response Interleukin-6 Knowledge Laboratories Life Link Longitudinal Studies Major Depressive Disorder Metric Moods Neuraxis Neurosecretory Systems Neurotic Disorders Paper Participant Pathogenesis Pathway interactions Personality Pneumococcal Pneumonia Predisposition Production Proteins Psyche structure Recording of previous events Relative Risks Reporting Research Personnel Risk Risk Factors Role Sampling Serotonin Serotonin Receptor 5-HT1A Serum Signal Transduction Spouse Caregiver Spouses Stress Stressful Event Susceptibility Gene Symptoms Syndrome TNF gene Testing Time Variant Wife Woman Work Wound Healing aging population caregiving cohort cytokine depression depressive symptoms disorder control environmental stressor experience inflammatory marker influenzavirus meetings men mortality negative mood physical conditioning programs prospective response stressor tumor young adult

项目摘要

DESCRIPTION (provided by applicant): A growing body of evidence has implicated dementia family caregiving as a risk factor for mental and physical health. Recent work provides evidence of one core pathway behind the diverse health risks associated with caregiving and other chronic stressors among older adults: sustained overproduction of a key proinflammatory cytokine, interleukin-6 (IL-6). This study will address whether genes for two proteins involved in serotonin (5-HT) signaling, the 5-HT transporter (5-HTT) and the 5-HT1A receptor, are susceptibility genes for depression and anxiety in 192 dementia spousal caregivers and 192 sociodemographically-matched noncaregiver controls. Use of a caregiver sample provides a way to replicate and extend key 5-HT vulnerability findings with a aging population that is clearly at risk; moreover, given the links between depression and enhanced secretion of IL-6 and tumor neurosis factor-alpha (TNF-a), we can also assess ties between genetic vulnerability to depression and overproduction of key proinflammatory cytokines. Additionally, this study will expand the well-documented associations between stress or depression and markers of inflammation by investigating the effects of depression, anxiety, and chronic stress on production of IL-6, CRP, and TNF-a, as well as the effect of genetic variation in these three markers on expression levels. Thus, we will also examine polymorphisms for IL-6, TNF-a, and CRP, and assess whether the differences in cytokine levels among the various groups (noncaregivers vs. caregivers, depression vs. no depression) are influenced by the cytokine genotypes, as well as relationships with age. Our specific aims are: 1) to determine if 5-HTT and the 5-HT1A receptor represent susceptibility genes for depression and anxiety among caregivers and noncaregiving controls; 2) to determine the effects of polymorphisms in the genes for IL-6, CRP, and TNF-a on the relationship between cytokine expression levels and depression and anxiety in caregivers and noncaregiver controls; 3) to determine the extent to which the chronic stresses of caregiving, depressive and anxiety symptoms, genetic vulnerability (polymorphisms for 5-HTT and 5-HT1A), and genetic variability (polymorphisms for IL-6, CRP, and TNF-a) influence proinflammatory responses following the occurrence of stressful life events; and 4) to determine the interactive contributions of age and distress to proinflammatory cytokine and CRP production. The proposed study will expand our knowledge of how genetic polymorphisms interact with environmental stressors to enhance risk for adverse mental and physical health changes.

描述（由申请人提供）：越来越多的证据暗示痴呆症家庭护理是精神和身体健康的危险因素。最近的工作提供了证明与护理和其他慢性压力相关的多种健康风险背后的核心途径：持续生产过多的关键促炎细胞因子，白介素6（IL-6）。这项研究将解决两种参与5-羟色胺（5-HT）信号传导，5-HT转运蛋白（5-HTT）和5-HT1A受体的蛋白质的基因，是192个痴呆症配偶护理人的抑郁和焦虑的易感基因，以及192社交人口统计学匹配的非护理人员对照。护理人员样本的使用提供了一种复制和扩展关键5-HT脆弱性发现的方法，其人口的老龄化显然处于危险之中；此外，鉴于抑郁症与IL-6的分泌增强与肿瘤神经症因子-Alpha（TNF-A）之间的联系，我们还可以评估遗传易受抑郁症与关键促炎细胞因子的过度生产之间的联系。此外，这项研究将通过研究抑郁症，焦虑和慢性应激对IL-6，CRP和TNF-A产生的影响以及效果，扩大压力或抑郁症之间有据可查的炎症之间的据可查的关联这三个标记在表达水平上的遗传变异。因此，我们还将检查IL-6，TNF-A和CRP的多态性，并评估各组之间的细胞因子水平差异（非照顾者与看护人，抑郁症与无抑郁症）受细胞因子基因型的影响，是细胞因子基因型的影响。以及与年龄的关系。我们的具体目的是：1）确定5-HTT和5-HT1A受体是否代表护理人员和非护理控制中抑郁和焦虑的易感基因； 2）确定IL-6，CRP和TNF-A基因中多态性对细胞因子表达水平与抑郁症与焦虑症之间的关系的影响； 3）确定护理，抑郁和焦虑症状的慢性应力，遗传脆弱性（5-HTT和5-HT1A的多态性）以及遗传变异性（IL-6，CRP和TNF-A的多态性）在发生压力大的生活事件发生后影响促炎的反应； 4）确定年龄和困扰对促炎性细胞因子和CRP产生的互动贡献。拟议的研究将扩大我们对遗传多态性如何与环境压力源相互作用的知识，以增加心理和身体健康的不良风险。