Sleep spindles in early course schizophrenia and first-degree relatives

早期精神分裂症及其一级亲属的睡眠纺锤波

• 批准号: 9702857
• 负责人: MATCHERI S. KESHAVAN
• 金额: $ 55.46万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-07 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9702857
• 关键词: Adolescence; Age; Antipsychotic Agents; Area; Biological Markers; Chronic; Cognition; Cognitive deficits; Cognitive remediation; Contralateral; Development; Early Intervention; Eszopiclone; Family; First Degree Relative; Functional disorder; General Hospitals; Hospitals; Impaired cognition; Impairment; Individual; Israel; Laboratories; Learning; Link; Literature; Massachusetts; Measures; Mediating; Medical center; Modeling; Motor; Neurobiology; Participant; Patients; Pilot Projects; Population; Predisposition; Prevention; Psychopathology; Psychotic Disorders; Recording of previous events; Relative Risks; Resistance; Risk; Sampling; Schizophrenia; Sleep; Sleep Deprivation; Sleep disturbances; Socioeconomic Status; Structure; Symptoms; Task Performances; Time; Work; base; cognitive function; density; effective therapy; emerging adult; endophenotype; executive function; experience; functional disability; functional outcomes; high risk; improved; memory consolidation; mental health center; neural correlate; neuroimaging; non rapid eye movement; novel; public health relevance; recruit; relating to nervous system; sex; sleep abnormalities; sleep spindle; trait

 DESCRIPTION (provided by applicant): A burgeoning literature suggests that sleep spindles mediate sleep-dependent memory consolidation and cognitive function more generally. At the same time, several recent studies show that sleep spindles are dramatically reduced in SZ. Cognitive deficits are a core feature of schizophrenia (SZ) that underlie significant functional disability and effective treatments are lacking. Previous work from our laboratories links the sleep spindle deficit with an impairment of sleep-dependent memory consolidation, IQ and executive function in SZ, and suggests that it is treatable. But it is unclear whether this sleep spindle deficit is present early in SZ, and whether it reflects a core disturbance central to its pathophysiology and familial risk of illness. In this study, we will examine sleep spindles, their relationship to memory consolidation and cognition more generally, and their neural underpinnings in early-course patients both with SZ (E-SZ; n=30), and with other psychoses (E-NSZ; n=30), in young relatives of SZ patients at familial high risk for SZ (FHR; n=60) and in healthy comparison (HC) subjects matched for age, sex and parental socioeconomic status. We hypothesize (i) that E-SZ and FHR, but not E-NSZ, will show reduced spindles compared with HC; (ii) that spindle number and density will correlate with sleep-dependent memory consolidation, IQ and overall cognitive function in all groups, and that deficient sleep spindles will correlate with positive and prodromal symptoms in E-SZ and FHR; and (iii) that during the sleep that follows motor task learning, HC and E-NSZ, but not E-SZ or FHR participants, will show increased spindle density and coherence, specifically in the motor network. We also predict that reduced spindle density will correlate with a reduction in thalamocortical functional and structural connectivity. Our hypotheses, if confirmed, will help establish the sleep spindle deficit as (i) an endophenotype of SZ, which can serve as a biomarker of familial risk (for studying the etiopathology of SZ), and (ii) a target for novel treatments of cognitive impairment.

 描述（由申请人提供）：一个新兴的文献表明，睡眠纺锤波介导睡眠依赖性记忆巩固和认知功能更普遍。与此同时，最近的几项研究表明，睡眠纺锤波在SZ中显着减少。认知缺陷是精神分裂症（SZ）的一个核心特征，是严重功能障碍的基础，缺乏有效的治疗方法。我们实验室以前的工作将睡眠纺锤体缺陷与SZ的睡眠依赖性记忆巩固、智商和执行功能受损联系起来，并表明它是可治疗的。但目前尚不清楚这种睡眠纺锤体缺陷是否存在于SZ的早期，以及它是否反映了其病理生理学和家族性疾病风险的核心障碍。在这项研究中，我们将研究睡眠纺锤波，它们与记忆巩固和认知的关系，以及它们在早期SZ患者中的神经基础。（E-SZ; n=30），并伴有其他精神病（E-NSZ; n=30），在SZ家族性高风险SZ患者的年轻亲属中（FHR; n=60）和在年龄、性别和父母社会经济地位匹配的健康对照（HC）受试者中。我们假设：（i）E-SZ和FHR，而不是E-NSZ，与HC相比，将显示出减少的纺锤波;（ii）纺锤波的数量和密度将与所有组的睡眠依赖性记忆巩固、智商和整体认知功能相关，并且睡眠纺锤波不足将与E-SZ和FHR的阳性和前驱症状相关;和（iii）在运动任务学习后的睡眠期间，HC和E-NSZ，而不是E-SZ或FHR参与者，将显示增加的纺锤体密度和连贯性，特别是在运动网络中。我们还预测，减少纺锤体密度将与丘脑皮质功能和结构连接的减少。我们的假设，如果得到证实，将有助于建立睡眠梭形缺陷作为（i）SZ的内在表型，可以作为家族风险的生物标志物（用于研究SZ的病因学），和（ii）认知障碍的新治疗的目标。