Vulnerability to major depression: The role of delta sleep in patients receiving

易患重度抑郁症：德尔塔睡眠对接受治疗的患者的作用

• 批准号: 8106346
• 负责人: FRANCIS E LOTRICH
• 金额: $ 31.56万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-06 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8106346
• 关键词: Adult; Alleles; Anger; Biological; Biological Markers; Brain; Circadian Rhythms; Clinical assessments; Communication; Cross-Sectional Studies; Data; Depressed mood; Development; Future; Genes; Genetic Polymorphism; Genetic Predisposition to Disease; Glucocorticoids; Hepatitis C; Hepatitis C virus; Human; Immune system; Incidence; Inflammation; Inflammatory; Influentials; Interferon-alpha; Interferons; Interleukin-6; Lead; Link; Major Depressive Disorder; Measures; Mediating; Mental Depression; Mental disorders; NIH Program Announcements; National Institute of Mental Health; Neuraxis; Pathway interactions; Patient Self-Report; Patients; Peripheral; Pharmacogenomics; Polysomnography; Population; Predictive Value; Prevention; Prevention strategy; Preventive Intervention; Process; Recruitment Activity; Relative (related person); Reporting; Resistance; Risk; Role; Self Assessment; Sleep; Sleep Architecture; Sleeplessness; Slow-Wave Sleep; Strategic Planning; Stress; Symptoms; Syndrome; Testing; Time; base; cytokine; density; depressive symptoms; design; disorder control; genetic variant; hazard; high risk; novel; prevent; promoter; public health relevance; serotonin transporter; sleep regulation

DESCRIPTION (provided by applicant): Delineating vulnerability to episodes of major depressive disorder (MDD) is important for designing and targeting preventive interventions. We are thus examining non-depressed adult people at high risk for depression and prospectively following for the incidence of an MDD episode. In particular, we are currently focusing on patients who have been prescribed interferon-alpha (IFN-a) for hepatitis C. Among patients not currently depressed, about 25% have elevated vulnerability and develop an MDD episode during subsequent IFN- a therapy. We have discovered that a major marker of vulnerability, observed prior to starting IFN- a, is poor self-reported sleep quality. Notably, poor sleep quality's relationship with vulnerability was independent from any other self-reported concurrent depression symptoms. Because delta (or 'slow wave') sleep has been associated with restorative processes in the brain, and low levels have been cross-sectionally observed during depression or insomnia, we hypothesize that low delta sleep power in non-depressed people is related to vulnerability for subsequent MDD. We will test this hypothesis by using polysomnography and power spectral analysis to examine non-depressed people before they start IFN- a. Well-characterized subjects will then be prospectively followed during treatment. Concurrently, we will examine potential influences on the sleep quality/MDD vulnerability relationship. One likely influence is interleukin-6 (IL-6), whose elevated daytime levels prior to treatment are associated with both worsening depression and sleep during IFN- a therapy. It is plausible that glucocorticoid resistance may lead to flattening of the circadian IL-6 rhythm, increased daytime levels, and impaired sleep regulation. Secondly, we and others have observed that promoter polymorphisms in the serotonin transporter may be associated with poor sleep quality, plausibly mediating their relationship to MDD. We also have preliminary evidence for other related genetic polymorphisms that may influence depression vulnerability via their effects on sleep. Our careful clinical assessment of the longitudinal relationships among depression, sleep, inflammatory cytokines, and genetic vulnerability in people receiving IFN- a could lead to novel targeted strategies for prevention of depression in the millions of people with hepatitis C, and could have broader relevance to depression prevention more generally. This high-impact agenda for this re-submission (MH090250-01-A1) coincides with the 2008 NIMH strategic plan to determine the biologic bases leading to MDD. PUBLIC HEALTH RELEVANCE: Delineating vulnerability to major depression is important for designing and targeting preventive interventions. We are thus examining non-depressed adult people at high risk for depression -- because they are prescribed interferon-alpha (IFN- a) for hepatitis C -- to determine whether differences in sleep predict who gets depressed. This may be a common pathway for genes, stress, and inflammation to influence risk for depression.

描述（由申请人提供）：描述重度抑郁症（MDD）发作的脆弱性对于设计和确定预防性干预措施非常重要。因此，我们正在检查患有抑郁症高风险的非抑郁成年人，并前瞻性地跟踪 MDD 发作的发生率。我们目前特别关注使用干扰素-α (IFN-a) 治疗丙型肝炎的患者。在目前没有抑郁症的患者中，约 25% 的患者易感性升高，并在随后的 IFN-a 治疗期间出现 MDD 发作。我们发现，在开始使用 IFN-α 之前观察到的脆弱性的一个主要标志是自我报告的睡眠质量差。值得注意的是，睡眠质量差与脆弱性的关系独立于任何其他自我报告的并发抑郁症状。由于 Delta（或“慢波”）睡眠与大脑的恢复过程相关，并且在抑郁或失眠期间横断面观察到低水平睡眠，因此我们假设非抑郁人群的低 Delta 睡眠能力与随后患 MDD 的脆弱性有关。我们将通过在非抑郁症患者开始使用 IFN-α 之前使用多导睡眠图和功率谱分析对他们进行检查来检验这一假设。然后在治疗期间对特征良好的受试者进行前瞻性随访。同时，我们将研究对睡眠质量/MDD 脆弱性关系的潜在影响。一个可能的影响是白细胞介素 6 (IL-6)，其治疗前白天水平升高与 IFN-α 治疗期间抑郁症和睡眠恶化有关。糖皮质激素抵抗可能会导致昼夜节律 IL-6 节律变平、白天水平升高以及睡眠调节受损。其次，我们和其他人观察到，血清素转运蛋白的启动子多态性可能与睡眠质量差有关，似乎介导了它们与 MDD 的关系。我们还有其他相关基因多态性的初步证据，这些多态性可能通过影响睡眠来影响抑郁症的易感性。我们对接受 IFN-α 治疗的抑郁症、睡眠、炎症细胞因子和遗传脆弱性之间的纵向关系进行了仔细的临床评估，可能会为数百万丙型肝炎患者制定新的有针对性的预防抑郁症的策略，并且可能与更广泛的抑郁症预防具有更广泛的相关性。此次重新提交的高影响力议程 (MH090250-01-A1) 与 2008 年 NIMH 确定导致 MDD 的生物学基础的战略计划相一致。 公共卫生相关性：描绘重度抑郁症的脆弱性对于设计和确定预防性干预措施非常重要。因此，我们正在检查患有抑郁症高风险的非抑郁成年人——因为他们服用了治疗丙型肝炎的α干扰素（IFN-a）——以确定睡眠差异是否可以预测谁会患上抑郁症。这可能是基因、压力和炎症影响抑郁风险的常见途径。