Sleep spindles in early course schizophrenia and first-degree relatives

 描述(由申请者提供)：一篇新兴的文献表明，睡眠纺锤波更广泛地调节了睡眠依赖记忆的巩固和认知功能。与此同时，最近的几项研究表明，在深圳，睡眠纺锤波显著减少。认知缺陷是精神分裂症(SZ)的一个核心特征，它是导致严重功能残疾的基础，缺乏有效的治疗。我们实验室以前的工作将睡眠纺锤体缺陷与SZ睡眠依赖记忆巩固、智商和执行功能的损害联系在一起，并表明它是可以治疗的。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，也不清楚它是否反映了以其病理生理学和家族疾病风险为中心的核心障碍。在这项研究中，我们将检查睡眠纺锤体，它们与记忆巩固和认知的更广泛的关系，以及它们的神经基础在早期SZ患者(E-SZ；n=30)和其他精神病患者(E-NSZ；n=30)中，在SZ患者家族高危的年轻亲属(FHR；n=60)和年龄、性别和父母社会经济状况匹配的健康对照(HC)受试者中。我们假设：(I)与HC相比，E-SZ和FHR的纺锤体数量和密度将减少；(Ii)纺锤体的数量和密度将与所有组的睡眠依赖记忆巩固、智商和整体认知功能相关，睡眠纺锤体不足将与E-SZ和FHR的阳性症状和前驱症状相关；(Iii)在运动任务学习之后的睡眠中，HC和E-NSZ的纺锤体密度和连贯性将增加，特别是在运动网络中。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性的降低相关。如果我们的假设得到证实，将有助于确定睡眠纺锤体缺陷是(I)SZ的一种内表型，它可以作为家族风险的生物标记物(用于研究SZ的病因)，以及(Ii)认知障碍的新治疗目标。

 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.