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: 9376357
• 负责人: Fabio Ferrarelli
• 金额: $ 41.19万
• 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 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9376357
• 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); Employee Strikes; Functional Magnetic Resonance Imaging; Functional disorder; Health; Health Care Costs; Impaired cognition; Impairment; Individual; Intervention; Longitudinal Studies; Magic; Magnetic Resonance Spectroscopy; Measures; Medial Dorsal Nucleus; 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 testing; 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; social; 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.

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 项目摘要：精神分裂症和相关疾病是全世界残疾的主要原因之一，因此 早期识别神经生物学脆弱性（可作为治疗目标）是一个关键 在最近的研究中，我们发现慢性精神分裂症患者在以下方面存在显着的缺陷。 睡眠纺锤波是第 2 阶段非快速眼动 (N2) 睡眠的标志，纺锤波很短（0.5-2 秒）， 12-16 Hz 范围内的渐强/渐弱振荡也出现在早期病程和早期阶段。 早发性精神分裂症和纺锤体相关测量，包括振幅、持续时间和密度， 与健康个体的认知能力、社会功能和神奇思维倾向相关， 通过调查个体主轴参数，我们确定了这一点。 纺锤体密度和振幅降低与症状和认知障碍的严重程度相关 我们还分别在慢性精神分裂症患者中发现了综合纺锤体活动（ISA）。 将各个主轴参数组合在一个值中，是最具辨别力的措施，产量约为 90% 精神分裂症和对照组之间的区别 临床高危青少年 (CHR) 是一个独特的人群。 丰富了主要精神疾病的前兆，例如精神分裂症，这些人也会经历紧急情况 我们不知道什么时候会出现认知障碍、社交功能障碍和亚综合征临床症状。 纺锤体损伤的发生，以及它们如何影响该人群精神病理学的发展。 因此，该项目的首要目标是表征睡眠纺锤波参数在调节睡眠中的作用。 CHR 青少年的认知、社会和临床功能轨迹，包括向精神病的转变。 睡眠纺锤波是由丘脑网状核 (TRN) 与背侧丘脑的相互作用启动的。 然后丘脑活动被传递到皮层，在那里纺锤体的振动是同步的。 纺锤体——密度、振幅和持续时间——反映丘脑、皮质和丘脑皮质的神经功能 此外，GABA 神经传递和丘脑皮质连接分别发挥着关键作用。 在最近的工作中，我们发现主轴缺陷最为严重。 额叶和前额叶头皮区域突出，丘脑内侧 (MD) 体积减少 与睡眠相关的精神分裂症源局部前额皮质（PFC）纺锤体减少。 根据这些发现，我们将整合多个分析层面的数据，从电生理学到神经学到 具体来说，是第二个广泛的目标。 该项目旨在利用睡眠高位来确定睡眠纺锤体缺陷的神经和分子基础 密度 (hd)-EEG、7T 静息态 (rs)-fMRI 和磁共振波谱成像 (MRSI)。 为了实现这些总体目标，我们建议对 45 个 CHR 和 45 个健康受试者进行纵向研究 对照（HC），在两年内对临床和认知功能、hd-EEG、fMRI 和 MRSI 进行三项评估。