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: 8240527
• 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/8240527
• 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）：描述对主要抑郁症发作（MDD）发作的脆弱性对于设计和靶向预防性干预措施很重要。因此，我们正在检查不抑郁的成年人患抑郁症的高风险，并前瞻性地跟随MDD发作的发生率。特别是，我们目前正在专注于针对乙型肝炎的干扰素 - α（IFN-A）处方的患者。在目前尚未抑郁的患者中，约25％的脆弱性升高并在随后的IFN-疗法期间发展为MDD发作。我们发现，在启动IFNA之前观察到的一个主要脆弱性标记是自我报告的睡眠质量差。值得注意的是，睡眠质量与脆弱性的关系差与任何其他自我报告的并发抑郁症状无关。由于三角洲（或“慢波”）睡眠与大脑的恢复过程有关，并且在抑郁症或失眠期间在横截面上观察到了较低的水平，因此我们假设非抑郁症患者中的三角洲睡眠能力低与随后MDD的脆弱性有关。我们将通过使用多肌仪和功率频谱分析来检验这一假设，以检查不抑郁的人在启动IFN-a之前。然后，在治疗期间将遵循良好特征的受试者。同时，我们将研究对睡眠质量/MDD脆弱性关系的潜在影响。可能的影响是白介素6（IL-6），其治疗前的白天水平升高与抑郁症恶化和IFN疗法期间的睡眠有关。糖皮质激素耐药性可能导致昼夜节律IL-6节奏，白天水平增加和睡眠调节受损。其次，我们和其他人观察到5-羟色胺转运蛋白中的启动子多态性可能与睡眠质量差有关，从而使它们与MDD的关系合理地介导。我们也有其他相关遗传多态性的初步证据，这些遗传多态性可能会通过对睡眠的影响影响抑郁症。我们仔细评估抑郁症，睡眠，炎症细胞因子和接受IFN的人的遗传脆弱性之间的纵向关系，可能会导致预防数百万丙型肝炎患者的抑郁症的新型策略，并且可以更广泛地预防抑郁症。该重新提交（MH090250-01-A1）的这一高影响力议程与2008年NIMH战略计划相吻合，以确定导致MDD的生物基础。 公共卫生相关性：描述对重度抑郁症的脆弱性对于设计和针对预防性干预措施很重要。因此，我们正在检查抑郁症高风险的不抑郁的成年人（因为他们的丙型肝炎处方干扰素 - α（IFN-A），以确定睡眠差异是否预测谁会抑郁。这可能是影响抑郁症风险的基因，压力和炎症的常见途径。