A spectrum of altered non-rapid eye movement sleep in schizophrenia.

IF 5.6 2区 医学 Q1 Medicine Sleep Pub Date : 2024-09-19 DOI:10.1093/sleep/zsae218
Nataliia Kozhemiako, Chenguang Jiang, Yifan Sun, Zhenglin Guo, Sinéad Chapman, Guanchen Gai, Zhe Wang, Lin Zhou, Shen Li, Robert G Law, Lei A Wang, Dimitrios Mylonas, Lu Shen, Michael Murphy, Shengying Qin, Wei Zhu, Zhenhe Zhou, Robert Stickgold, Hailiang Huang, Shuping Tan, Dara S Manoach, Jun Wang, Mei-Hua Hall, Jen Q Pan, Shaun M Purcell
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Abstract

Multiple facets of sleep neurophysiology, including electroencephalography (EEG) metrics such as non-rapid eye movement (NREM) spindles and slow oscillations, are altered in individuals with schizophrenia (SCZ). However, beyond group-level analyses, the extent to which NREM deficits vary among patients is unclear, as are their relationships to other sources of heterogeneity including clinical factors, ageing, cognitive profiles and medication regimens. Using newly collected high-density sleep EEG data on 103 individuals with SCZ and 68 controls, we first sought to replicate our previously reported group-level differences between patients and controls (original N=130) during N2 stage. Then in the combined sample (N=301 including 175 patients), we characterized patient-to-patient variability. We replicated all group-level mean differences and confirmed the high accuracy of our predictive model (AUC=0.93 for diagnosis). Compared to controls, patients showed significantly increased between-individual variability across many (26%) sleep metrics. Although multiple clinical and cognitive factors were associated with NREM metrics, collectively they did not account for much of the general increase in patient-to-patient variability. Medication regimen was a greater contributor to variability. Some sleep metrics including fast spindle density showed exaggerated age-related effects in SCZ, and patients exhibited older predicted biological ages based on the sleep EEG; further, among patients, certain medications exacerbated these effects, in particular olanzapine. Collectively, our results point to a spectrum of N2 sleep deficits among SCZ patients that can be measured objectively and at scale, with relevance to both the etiological heterogeneity of SCZ as well as potential iatrogenic effects of antipsychotic medication.

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精神分裂症患者非快速眼动睡眠的改变谱系。
精神分裂症(SCZ)患者的睡眠神经生理学的多个方面,包括脑电图(EEG)指标,如非快速眼动(NREM)棘波和慢振荡,都会发生改变。然而,除了群体层面的分析之外,非快速眼动缺陷在患者之间的差异程度还不清楚,它们与其他异质性来源的关系也不清楚,这些异质性来源包括临床因素、年龄、认知状况和药物治疗方案。利用新收集的103名SCZ患者和68名对照组患者的高密度睡眠脑电图数据,我们首先试图复制之前报道的患者和对照组(原始样本数=130)在N2阶段的组间差异。然后,在合并样本(N=301,包括 175 名患者)中,我们描述了患者之间的变异性。我们复制了所有组别的平均差异,并证实了我们的预测模型具有很高的准确性(诊断的 AUC=0.93)。与对照组相比,患者在多项(26%)睡眠指标上的个体间变异性明显增加。虽然多种临床和认知因素与 NREM 指标相关,但总体而言,这些因素并不能解释患者间变异性的普遍增加。用药方案是造成变异的主要原因。包括快速纺锤体密度在内的一些睡眠指标在SCZ患者中显示出与年龄相关的夸张效应,而且根据睡眠脑电图,患者显示出较高的预测生物年龄;此外,在患者中,某些药物会加剧这些效应,尤其是奥氮平。总之,我们的研究结果表明,SCZ 患者的 N2 睡眠缺陷是可以客观测量的,与 SCZ 的病因异质性以及抗精神病药物的潜在先天效应都有关系。
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来源期刊
Sleep
Sleep Medicine-Neurology (clinical)
CiteScore
8.70
自引率
10.70%
发文量
0
期刊介绍: SLEEP® publishes findings from studies conducted at any level of analysis, including: Genes Molecules Cells Physiology Neural systems and circuits Behavior and cognition Self-report SLEEP® publishes articles that use a wide variety of scientific approaches and address a broad range of topics. These may include, but are not limited to: Basic and neuroscience studies of sleep and circadian mechanisms In vitro and animal models of sleep, circadian rhythms, and human disorders Pre-clinical human investigations, including the measurement and manipulation of sleep and circadian rhythms Studies in clinical or population samples. These may address factors influencing sleep and circadian rhythms (e.g., development and aging, and social and environmental influences) and relationships between sleep, circadian rhythms, health, and disease Clinical trials, epidemiology studies, implementation, and dissemination research.
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