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

基本信息

批准号：
9139499
负责人：
MATCHERI S. KESHAVAN
金额：
$ 62.48万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-07 至 2020-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9139499
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 Health 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 Recruitment Activity Relative Risks Resistance Risk Sampling Schizophrenia Sleep Sleep disturbances Socioeconomic Status Staging 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 relating to nervous system sex trait

项目摘要

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）：新兴文献表明，睡眠纺锤波更普遍地介导睡眠依赖性记忆巩固和认知功能。同时，最近的几项研究表明，睡眠纺锤波在 SZ 中显着减少，这是一个核心特征。我们实验室之前的研究缺乏将睡眠纺锤波缺陷与睡眠依赖性记忆巩固、智商和执行功能损害联系起来的精神分裂症（SZ）的严重功能障碍和有效的治疗方法。但尚不清楚这种睡眠纺锤波缺陷是否存在于 SZ 早期，以及它是否反映了其病理生理学和家族疾病风险的核心紊乱。纺锤体，它们与记忆巩固和认知的关系，以及它们在 SZ（E-SZ；n=30）和其他精神病（E-NSZ；n=30）早期病程患者中的神经基础。 n = 30），在 SZ 家族高风险的 SZ 患者的年轻亲属中（FHR；n = 60）以及年龄、性别和父母社会经济状况匹配的健康对照（HC）受试者，但不匹配 E-。与 HC 相比，NSZ 会显示纺锤波减少；(ii) 纺锤波数量和密度将与所有组中的睡眠依赖性记忆、智商和整体认知功能相关，并且睡眠纺锤波不足将导致与 E-SZ 和 FHR 中的阳性和前驱症状相关；(iii) 在运动任务学习后的睡眠期间，HC 和 E-NSZ（而非 E-SZ 或 FHR 参与者）将表现出纺锤体密度和连贯性增加，我们还预测，纺锤体密度的降低将与丘脑皮质功能和结构连接的减少相关，如果得到证实，我们的假设将有助于将睡眠纺锤体缺陷确定为 (i) SZ 的内表型。可以作为家族风险的生物标志物（用于研究 SZ 的病因病理学），以及 (ii) 认知障碍新疗法的目标。