Prospective Study of Depressed Mood, Short Sleep and Serotonergic Genes

抑郁情绪、短睡眠和血清素基因的前瞻性研究

• 批准号: 7581372
• 负责人: Mary A Carskadon
• 金额: $ 57.39万
• 依托单位: EMMA PENDLETON BRADLEY HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-19 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7581372
• 关键词: Adolescent; Affect; Alcohol consumption; Alleles; Behavioral; Buspirone; Chronic; Circadian Rhythms; Data; Depressed mood; Development; Diagnostic; Electroencephalography; Enrollment; Epidemiologic Studies; Event; Face; Family; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Genotype; Hydrocortisone; Individual; Internet; Knowledge; Laboratories; Lead; Life; Link; Major Depressive Disorder; Mediating; Mental Health; Mood Disorders; Moods; Natural experiment; Nature; Outcome; Participant; Patients; Pattern; Performance; Phase; Phase I Clinical Trials; Phenotype; Precipitating Factors; Predisposition; Prevention; Promoter Regions; Prospective Studies; Questionnaires; REM Sleep; Rattus; Receptor Gene; Recording of previous events; Relative (related person); Reporting; Role; Sampling; Screening procedure; Serotonin; Serotonin Receptor 5-HT1A; Sleep; Sleep Stages; Sleeplessness; Slow-Wave Sleep; Stress; Structure; Students; Subgroup; Surveys; Symptoms; System; Testing; Therapeutic; Time; Universities; Variant; base; biobehavior; center for epidemiological studies depression scale; cohort; college; depressed; depression; depressive symptoms; desensitization; diaries; experience; pediatric trauma; preference; prospective; public health relevance; receptor; receptor sensitivity; research study; response; serotonin 5 receptor; serotonin transporter; suicidal risk; university student; young adult

DESCRIPTION (provided by applicant): This proposal is a revised submission of a project whose principal aim is to assess prospectively the association between reduced sleep and depressed mood. As many as 20% of college students suffer from depressed mood, and mood problems are considered among the top 5 impediments to academic performance. We propose that short sleep may be a precipitating factor for depressed mood in young adults, a link mediated by the serotonin system. Depression and short sleep have both been associated with insensitivity of the serotonin 1A receptor. Indeed, depression is favored by certain polymorphisms of the serotonin 1A receptor gene and serotonin transporter gene, and these variations may indicate vulnerability for depression or depressed mood in the context of chronically restricted sleep. Study 1. A prospective study follows students before college through the first semester of their freshman collegiate year in several annual cohorts from a residential Ivy League university and a small local chiefly "commuter" college. Students' pre-collegiate reported total sleep time will be used to stratify healthy, nondepressed young people in the collegiate samples. Daily sleep/wake diaries completed on the web, along with genotyping for the serotonin "vulnerability" markers will be examined in students found with and without depressed mood using the Center for Epidemiological Studies-Depression (CES-D) scale in the eighth week of the college semester. Symptoms of depression and other mental health conditions will be assessed with the Psychiatric Diagnostic Screening Questionnaire (PDSQ) at three time points (pre- collegiate, enrollment, and 8 weeks). Markers of the circadian timing system and alcohol use data will also be examined, along with family and life-time history of depression, childhood trauma, and stress-related susceptibility to insomnia (in contrast to `volitional' short sleep). Additional psychiatric co-morbid symptoms will be assessed using the PDSQ. Study 2. A second study will assess the sensitivity of the serotonin 1A receptor with a pharmacological (buspirone) challenge, in which blunting of the hypothermic and cortisol responses are expected in the students who have depressed mood and short sleep, particularly when associated with specific serotonin transporter and/or 1A receptor polymorphisms. This test will help to confirm whether an association of depressed mood and short sleep is related to altered serotonin sensitivity. Study 3. Sleep structure will be analyzed in a subgroup of participants from Study 1 to examine whether sleep structure changes previously associated with major depressive disorder are associated with depressed mood, short sleep, and genetic vulnerability. PUBLIC HEALTH RELEVANCE: This project will examine whether chronically reduced sleep can lead to depressed mood in college students, which is a serious concern as an impediment to academic performance and a risk for suicide. These studies will examine whether students are susceptible to depression if they have the combination of a certain genetic background and then get too little sleep; additional tests will examine whether the association of too little sleep and depressed mood is related the serotonin system and whether sleep structure is affected. Such knowledge can help target prevention for the development of depressed mood in young people undergoing a major stressful life event.

描述（由申请人提供）：该提案是一个项目的修订，其主要目的是评估睡眠减少与情绪低落之间的关联。多达20％的大学生情绪低落，情绪问题被认为是学习成绩的前5名障碍之一。我们建议短暂的睡眠可能是年轻人情绪低落的促成因素，这是5-羟色胺系统介导的链接。抑郁和短睡眠都与5-羟色胺1A受体的不敏感性有关。的确，抑郁症受到5-羟色胺1A受体基因和5-羟色胺转运蛋白基因的某些多态性的青睐，这些变化可能表明在长期受到限制的睡眠的背景下，抑郁症或情绪低落。研究1。一项前瞻性研究跟踪大学前的学生在新生大学的第一学期之前，每年的同一年级众多同胞，来自一所住宅常春藤联盟大学和一所小型当地的主要“通勤”学院。学生的学前班报告称，总的睡眠时间将用于对大学样本中健康，不抑郁的年轻人进行分层。每天在网络上完成的每日睡眠/唤醒日记，以及在大学学期第八周的流行病学研究抑郁症中心（CES-D）量表中，将在学生和没有情绪低落的学生中检查5-羟色胺“脆弱性”标记的基因分型。抑郁症和其他心理健康状况的症状将在三个时间点（大学前，入学和8周）的精神诊断筛查问卷（PDSQ）评估。还将检查昼夜节律定时系统和饮酒数据的标志物，以及抑郁症，儿童创伤的家庭和终身历史，以及与压力有关的失眠症的敏感性（与“自愿”短睡眠相反）。将使用PDSQ评估其他精神病症状。研究2。第二项研究将评估血清素1a受体的敏感性，并具有药理学（丁螺酮）挑战，其中在情绪低落和睡眠较短的学生中，预计低温和皮质醇反应的趋势会降低，尤其是与特定的5-羟色胺转运蛋白和/或1A受体受体多态性相关的学生。该测试将有助于确认情绪低落和短睡眠的关联是否与5-羟色胺敏感性的改变有关。研究3。将在研究1的参与者的子组中分析睡眠结构，以检查先前与重度抑郁症相关的睡眠结构变化是否与情绪低落，睡眠短和遗传脆弱性有关。公共卫生相关性：该项目将检查长期减少的睡眠是否会导致大学生心情沮丧，这是一个严重的关注，这是对学业表现和自杀风险的障碍。这些研究将检查学生是否有某种遗传背景的组合而睡眠太少，是否容易受到抑郁的影响。其他测试将检查睡眠和情绪低落的关联是否与5-羟色胺系统以及睡眠结构相关。这种知识可以帮助预防预防，以发展年轻人经历重大压力生活事件的年轻人。