Characterize differences in sleep spindles between Clinical High Risk and healthy controls longitudinally.

纵向描述临床高风险组和健康对照组之间睡眠纺锤波的差异。

• 批准号: 9750107
• 负责人: Fabio Ferrarelli
• 金额: $ 53.79万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-20 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9750107
• 关键词: Address; Adolescent and Young Adult; Affect; Attenuated; Cell Nucleus; Characteristics; Chronic; Chronic Schizophrenia; Clinical; Clinical assessments; Cognitive; Control Groups; Data; Defect; Development; Disease; Disease remission; Dorsal; Early Intervention; Early identification; Electroencephalography; Electrophysiology (science); Functional Magnetic Resonance Imaging; Functional disorder; Health Care Costs; Healthcare; Impaired cognition; Impairment; Individual; Intervention; Longitudinal Studies; Magic; Magnetic Resonance Spectroscopy; Measures; Mental disorders; Modeling; Molecular; Neurobiology; Neurons; Neurophysiology - biologic function; Participant; Patients; Performance; Play; Population; Prefrontal Cortex; Psychopathology; Psychotic Disorders; Public Health; Relative Risks; Research Priority; Rest; Risk Factors; Role; Sampling; Scalp structure; Scanning; Schizophrenia; Schizotypal Personality Disorder; Severities; Sleep; Social Functioning; Societies; Source; Structure; Symptoms; Syndrome; Testing; Thalamic structure; Thinking; Waxes; Work; Youth; base; clinical care; clinical risk; cognitive ability; cognitive function; density; disability; early onset; experience; follow up assessment; functional disability; gamma-Aminobutyric Acid; high risk; in vivo; innovation; insight; longitudinal analysis; longitudinal design; neural circuit; neurophysiology; neurotransmission; non rapid eye movement; novel; relating to nervous system; sleep spindle; social; social deficits; source localization; spectroscopic imaging; symptomatology; trait

Characterize differences in sleep spindles between Clinical High Risk and healthy controls longitudinally Project summary: Schizophrenia and related disorders are one of leading causes of disability worldwide, thus making the early identification of neurobiological vulnerabilities, which may serve as treatment targets, a critical research priority. In recent work, we found that individuals with chronic schizophrenia had a striking deficit in sleep spindles. A hallmark of Stage 2 Non-Rapid Eye Movement (N2) Sleep, spindles are short (0.5-2 s), waxing/waning oscillations within the 12-16 Hz range. Spindle abnormalities are also present in early course and early onset schizophrenia, and spindle-related measures, including amplitude, duration, and density, are associated with cognitive ability, social functioning, and tendency for magical thinking in healthy individuals, including adolescents and young adults. By investigating individual spindle parameters, we established that reduced spindle density and amplitude are associated with severity of symptoms and cognitive impairments respectively, in chronic schizophrenia patients. We also found that Integrated Spindle Activity (ISA), which combines individual spindle parameters in a single value, was the most discriminating measure, yielding ~90% separation between schizophrenia and control groups. Youth at Clinical High Risk (CHR) are a unique population enriched for precursors of major psychiatric disorders, such as schizophrenia, who also experience emergent cognitive impairments, social dysfunction, and sub-syndromal clinical symptoms. What we do not know is when spindle impairments occur, and how they may affect the development of psychopathology in this population. Thus, the first broad aim of this project is to characterize the role of sleep spindle parameters in moderating cognitive, social, and clinical functioning trajectories, including transition to psychosis, among youth at CHR. Sleep spindles are initiated by the interplay of the Thalamic Reticular Nucleus (TRN) with the dorsal thalamus. Thalamic activity is then relayed to the cortex, where spindle oscillations are synchronized. Specific features of spindles—density, amplitude and duration—reflect neural function in the thalamus, cortex, and thalamo-cortical connections, respectively. Moreover, GABA neurotransmission and thalamo-cortical connectivity play a critical role in generating and sustaining spindle oscillations. In recent work, we found that spindle deficits were most prominent in frontal and prefrontal scalp regions, and that reduced medio-dorsal (MD) thalamic volumes were associated with decreased sleep spindles in source localized prefrontal cortex (PFC) in schizophrenia. Building on these findings, we will integrate data across multiple levels of analysis, from electrophysiology to neural to molecules, to characterize this spindle-related thalamo-cortical circuitry. Specifically, the second broad aim of this project is to identify the neuronal and molecular underpinnings of sleep spindle defects using sleep high density (hd)-EEG, 7T resting state (rs)-fMRI, and Magnetic Resonance Spectroscopy Imaging (MRSI). In order to address these general aims, we propose to conduct longitudinal studies in 45 CHR and 45 healthy controls (HC), with three assessments of clinical and cognitive function, hd-EEG, fMRI, and MRSI over two years.

表征临床高风险和健康对照之间的睡眠纺锤体差异纵向 项目摘要：精神分裂症和相关疾病是全球残疾的主要原因之一，因此 使神经生物学脆弱性的早期识别可能充当治疗目标，这是关键的 研究优先。在最近的工作中，我们发现患有慢性精神分裂症的人在 睡眠主轴。第2阶段非比型眼运动（N2）睡眠的标志，纺锤体短（0.5-2 s）， 在12-16 Hz范围内的打蜡/衰减振荡。纺锤体异常也存在于早期课程中，并且 早期发作精神分裂症和与纺锤相关的措施（包括放大器，持续时间和密度）是 与认知能力，社会功能和健康个体魔法思维的趋势有关， 包括青少年和年轻人。通过调查单个主轴参数，我们确定了 降低的主轴密度和放大器与符号和认知障碍的严重程度有关 分别在慢性精神分裂症患者中。我们还发现集成主轴活动（ISA）， 在单个值中结合单个主轴参数是最有区别的测量值，产生了〜90％ 精神分裂症和对照组之间的分离。临床高风险（CHR）的青年是独特的人群 富含精神分裂症等主要精神疾病的前体，他们也经历了新兴 认知障碍，社会功能障碍和亚综合临床症状。我们不知道什么时候 主轴损伤发生，以及它们如何影响该人群的心理病理学发展。 这是该项目的第一个广泛目的是表征睡眠主轴参数在调节中的作用 Chr的年轻人中的认知，社会和临床功能轨迹，包括向精神病的过渡。 睡眠纺锤是由丘脑网状核（TRN）与背丘脑的相互作用引发的。 然后将丘脑活性中继到皮层，并在该皮层中同步。特定功能 纺锤体 - 密度，放大器和持续时间 - 丘脑，皮质和丘脑皮层的神经功能 连接分别。此外，GABA神经传递和Thalamo-cortical连通性起着至关重要的作用 在产生和维持主轴振荡中的作用。在最近的工作中，我们发现主轴定义最多 在额叶和前额叶头皮区域中突出，而丘脑的中质（MD）减少为 与精神分裂症的局部局部前额叶皮层（PFC）中的睡眠纺锤体减少有关。建筑 根据这些发现，我们将整合跨多个分析的数据，从电生理学到神经元到 分子，以表征与纺锤相关的丘脑皮层电路。具体而言，第二个范围的目标 该项目是识别使用高睡眠的睡眠纺锤体缺陷的神经元和分子基础 密度（HD）-EEG，7T静止状态（RS）-FMRI和磁共振光谱成像（MRSI）。 为了解决这些总体目标，我们建议在45个CHR和45个健康中进行纵向研究 对照（HC），对临床和认知功能进行了三次评估，HD-EEG，fMRI和MRSI在两年内。