Experimental Model of Depression in Aging: Insomnia, Inflammation, and Affect Mechanisms

衰老过程中抑郁症的实验模型：失眠、炎症和影响机制

• 批准号: 9925164
• 负责人: Michael R Irwin
• 金额: $ 55.27万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9925164
• 关键词: Acute; Affect; Affective; Aging; Antidepressive Agents; Biological; Brain region; Chronic; Clinical; Coupled; Cytokine Gene; Development; Disease; Disease remission; Dose; Double-Blind Method; Elderly; Emotions; Endotoxins; Experimental Models; Face; Feeling; Fibrinogen; Genetic Polymorphism; Immune response; Infection; Inflammation; Inflammatory; Inflammatory Response; Intervention; Ketamine; Learning; Measures; Mental Depression; Modeling; Molecular Target; Monitor; Morbidity - disease rate; Older Population; Patient Self-Report; Pharmacology; Placebos; Preventive Intervention; Public Health; Randomized; Recurrence; Rewards; Risk; Sex Differences; Signal Transduction; Sleep disturbances; Sleeplessness; Stress; Translating; Woman; base; depressed patient; depression model; depression prevention; depressive symptoms; effective intervention; emotion regulation; geriatric depression; high risk population; improved; men; mortality; negative affect; prevent; primary outcome; prospective; response; reward processing; sex; sleep behavior; social

Depression, one of the most common diseases in older adults, carries significant risk for morbidity and mortality. Because of the burgeoning population of older adults, the enormous burden of late-life depression, and the limited efficacy of current antidepressants in older adults, biologically plausible models that translate into depression prevention efforts are needed. Insomnia predicts depression recurrence, and is a modifiable target for depression prevention. Yet, it is not known how insomnia gets converted into biological- and affective risk for depression, which is critical for identification of molecular targets for pharmacologic interventions, and for refinement of insomnia treatments that target affective responding to improve efficacy. This study will use an inflammatory challenge (i.e., endotoxin) to probe acute inflammatory- and depression responses (primary outcome) in older adults as a function of insomnia. Older adults with insomnia show chronic inflammation; sleep disturbance also activates inflammatory signaling; chronic inflammation primes acute inflammatory responses; chronic inflammation, as well as acute inflammatory reactivity, predict depression over the following year; and finally, endotoxin induces acute inflammation along with depressive symptoms, with preliminary evidence that “two-hits” (i.e., sleep disturbance and inflammatory challenge) are associated with exaggerated increases in depression, especially in women. In this placebo-controlled, randomized, double-blind study of low dose endotoxin in older adults (60-80 y; stratified by sex) with insomnia (n=80) vs. comparisons without insomnia (n=80), we hypothesize that older adults with insomnia will show heightened inflammatory- and affective responding to inflammatory challenge as compared to those without insomnia. We aim to: 1) examine differences in depressive symptoms and measures of negative affect responding as a function of insomnia and inflammatory challenge; 2) examine differences in measures of positive affect responding as a function of insomnia and inflammatory challenge; and 3) examine differences in experimentally-induced inflammation in relation to depressive symptoms and measures of negative- and positive affect responding as a function of insomnia. If the hypotheses are confirmed, older adults with two “hits”, insomnia and inflammation, would represent a high risk group to be prioritized for monitoring and for depression prevention efforts using treatments that target insomnia or inflammation. Moreover, this study will inform the development of mechanism-based treatments that target affect responses in addition to sleep behaviors, and which might also be coupled with efforts to reduce inflammation to optimize efficacy of depression prevention.

抑郁症是老年人最常见的疾病之一，有很大的发病和死亡风险