Risk Genes for Late-Life Depression after Hip Fracture

髋部骨折后晚年抑郁症的风险基因

• 批准号: 8033176
• 负责人: Eric J Lenze
• 金额: $ 37.37万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8033176
• 关键词: Acute; Affect; Aging; Alleles; Biological; Blood specimen; Brain-Derived Neurotrophic Factor; Butter; Censuses; Clinical Research; Cognitive; Collaborations; Comorbidity; DNA; Data; Data Set; Delirium; Diagnostic; Dinucleotide Repeats; Doctor of Medicine; Doctor of Philosophy; Elderly; Environmental Risk Factor; Epidemic; Etiology; Event; Future; Genes; Genetic; Genetic Polymorphism; Genetic Research; Genetic Risk; Genetic Techniques; Genetic screening method; Genotype; Geriatrics; Grant; HTR2A gene; Hip Fractures; Human Genetics; Individual; Institutionalization; Investigation; Lead; Life; Link; Measures; Medical; Mental Depression; Mental disorders; Methods; Modeling; Molecular Genetics; National Institute of Mental Health; Occupational Therapy; Other Genetics; Pain; Pathogenesis; Patients; Personality; Persons; Pharmaceutical Preparations; Physical Medicine; Population; Prevention; Prevention strategy; Preventive; Psychiatry; Quality of life; Recording of previous events; Recovery of Function; Recruitment Activity; Rehabilitation therapy; Research; Research Methodology; Research Personnel; Resources; Risk; Risk Factors; Sampling; Sampling Studies; Serotonin; Severities; Social Change; Social support; Symptoms; System; Testing; Tryptophan; Universities; Washington; Work; age related; comparison group; depressive symptoms; disability; disorder prevention; follow-up; gene environment interaction; genetic analysis; geriatric depression; health care service utilization; high risk; improved; innovation; medical schools; mortality; non-genetic; outcome forecast; prevent; programs; promoter; psychogenetics; psychologic; public health relevance; serotonin transporter; social; stressor; translational neuroscience; treatment strategy

DESCRIPTION (provided by applicant): Disabling medical events are a major risk factor for late-life depression (LID), which in turn leads to poor functional recovery and increased mortality. Effective prevention of LLD in this setting requires research on its etiology and risk factors. Thus, we will examine genetic polymorphisms in the serotonergic system, and psychological, social, and aging-related factors as risk factors for the onset of LLD after a hip fracture, a severe and disabling event. In our pilot work, the serotonin transporter promoter polymorphism (5-HTTLPR) s allele and the 5-HT2a (-1438)A/G allele were associated with an increased likelihood of LLD and/or higher levels of depressive symptoms after hip fracture. This grant integrates clinical research methods for assessing LLD with state of the art genetic methods. We will examine association of five genetic polymorphisms in the serotonin system (5-HTTLPR, 5-HT2a (-1438)A/G, 5-HT1a (-1019)C/G, TPH-2 (1463)G/A and BDNF dinucleotide repeat) with the onset and course of LLD in 470 elderly persons who have had a hip fracture. We will collect samples for genotyping, and we will follow subjects for one year. We will longitudinally assess LLD as well as variables related to vulnerability to LLD (e.g., cognitive status, disability, medical and psychiatric comorbidity, medication use, and life events). We will collect the same information over one year on a comparison group of 100 elderly persons who have not suffered a hip fracture. We hypothesize that these polymorphisms will be associated with LLD in the hip fracture group. Beyond the testing of study hypotheses, we will model risk for LLD using both genetic and non-genetic factors (e.g., vulnerability due to personality, disposition, or prior depression; age-related changes; social support). We will replicate genetic results in a second sample of hip fracture subjects. Data and samples from this study will be made available for future genetic studies, by our group as well as other investigators. The public health relevance is great, as LLD is a devastating and difficult-to-treat illness. The proposed research will be essential to reducing the burden of LLD by improving our understanding of the etiology of this illness: additionally, findings from this research could lead risk profiling using genetic and other risk factors, a necessary step for prevention.

描述（由申请人提供）：致残医疗事件是晚年抑郁症 (LID) 的主要危险因素，进而导致功能恢复不良和死亡率增加。在这种情况下有效预防 LLD 需要对其病因和危险因素进行研究。因此，我们将检查血清素系统中的遗传多态性，以及心理、社会和衰老相关因素，作为髋部骨折（一种严重致残事件）后 LLD 发生的危险因素。在我们的试点工作中，血清素转运蛋白启动子多态性 (5-HTTLPR) s 等位基因和 5-HT2a (-1438)A/G 等位基因与髋部骨折后 LLD 的可能性增加和/或更高水平的抑郁症状相关。该资助将评估 LLD 的临床研究方法与最先进的遗传方法相结合。我们将检查血清素系统中五种遗传多态性的关联（5-HTTLPR、5-HT2a (-1438)A/G、5-HT1a (-1019)C/G、TPH-2 (1463)G/A 和 BDNF二核苷酸重复）与 470 名髋部骨折老年人的 LLD 的发病和病程有关。我们将收集样本进行基因分型，并对受试者进行为期一年的跟踪。我们将纵向评估 LLD 以及与 LLD 脆弱性相关的变量（例如认知状态、残疾、医疗和精神合并症、药物使用和生活事件）。我们将在一年内收集 100 名未发生髋部骨折的老年人作为对照组的相同信息。我们假设这些多态性与髋部骨折组的 LLD 相关。除了测试研究假设之外，我们还将利用遗传和非遗传因素（例如，由于性格、性情或既往抑郁症而导致的脆弱性；与年龄相关的变化；社会支持）来模拟 LLD 的风险。我们将在髋部骨折受试者的第二个样本中复制遗传结果。本研究的数据和样本将由我们的小组以及其他研究人员用于未来的基因研究。由于 LLD 是一种毁灭性且难以治疗的疾病，因此与公共卫生相关性很大。拟议的研究对于通过提高我们对这种疾病病因学的理解来减轻 LLD 的负担至关重要：此外，这项研究的结果可能会导致使用遗传和其他风险因素进行风险分析，这是预防的必要步骤。

项目成果

Fear of Falling after Hip Fracture: Prevalence, Course, and Relationship with One-Year Functional Recovery.

髋部骨折后对跌倒的恐惧：患病率、病程以及与一年功能恢复的关系。

• 发表时间: 2016-12
• 作者: Bower, Emily S;Wetherell, Julie Loebach;Petkus, Andrew J;Rawson, Kerri S;Lenze, Eric J
• 通讯作者: Lenze, Eric J

Predictors of Posttraumatic Stress Symptoms and Association with Fear of Falling After Hip Fracture.

创伤后应激症状的预测因素以及与髋部骨折后跌倒恐惧的关联。

• 发表时间: 2017-06
• 影响因子: 6.3
• 作者: Kornfield, Sara L;Lenze, Eric J;Rawson, Kerri S
• 通讯作者: Rawson, Kerri S

A new measure of fear of falling: psychometric properties of the fear of falling questionnaire revised (FFQ-R).

跌倒恐惧的新衡量标准：跌倒恐惧问卷修订版的心理测量特性（FFQ-R）。

• 发表时间: 2015-07
• 影响因子: 7
• 作者: Bower, Emily S;Wetherell, Julie Loebach;Merz, C Caroline;Petkus, Andrew J;Malcarne, Vanessa L;Lenze, Eric J
• 通讯作者: Lenze, Eric J

Short-term affective recovery from hip fracture prospectively predicts depression and physical functioning.

髋部骨折的短期情感恢复可以前瞻性地预测抑郁和身体功能。

• 发表时间: 2015-01
• 作者: Langer, Julia K;Weisman, Jaclyn S;Rodebaugh, Thomas L;Binder, Ellen F;Lenze, Eric J
• 通讯作者: Lenze, Eric J

Cognitive Improvement in Older Adults in the Year After Hip Fracture: Implications for Brain Resilience in Advanced Aging.

髋部骨折后一年老年人的认知改善：对晚期衰老中大脑恢复能力的影响。

• 发表时间: 2018
• 作者: Oughli, Hanadi Ajam;Chen, Gengsheng;Philip Miller, J;Nicol, Ginger;Butters, Meryl A;Avidan, Michael;Stark, Susan;Lenze, Eric J
• 通讯作者: Lenze, Eric J