Au Chi Hung, Harvey Christopher-James
Queen Mary Hospital, Hong Kong.
Imperial College London, UK.
Sleep Med X. 2020 Aug 29;2:100025. doi: 10.1016/j.sleepx.2020.100025. eCollection 2020 Dec.
Sleep disturbances are associated with worse cognitive and psychotic symptoms in individuals with schizophrenia. Growing literature reveals sleep spindle deficits in schizophrenia may be an endophenotype reflecting a dysfunctional thalamo-thalamic reticular nucleus-cortical circuit. Since thalamic functions link to cognitive, positive and negative symptoms, it is possible that sleep spindle activity is associated with these symptoms. The primary objectives of this systematic review were to assess the associations of sleep spindle activity in psychotic patients with 1) cognitive functions; and 2) positive and negative symptom severity. A secondary objective was to examine which spindle parameter would be the most consistent parameter correlating with cognitive functions, and positive and negative symptoms.
Observational studies reporting an association between sleep spindle activity and cognitive functions, positive and negative symptoms in patients with psychotic disorders were considered eligible. We developed a comprehensive electronic search strategy to identify peer-reviewed studies in Pubmed, Embase, PsycINFO and CINAHL covering all dates up to the search date in May 2020 with no language restriction. The references of published articles were hand-searched for additional materials. The authors of published articles were contacted for newer or unpublished data. Risk of bias was assessed by Appraisal of Cross-sectional Studies (AXIS).
A total 11 cross-sectional studies (n = 255) with low-to-moderate quality, were selected for the systematic review. 8 of them addressed the association between sleep spindle activity and cognitive functions (n = 193), of which 6 studies reported positive correlations (r only reported in 4 studies, from 0.45 to 0.75). Out of multiple cognitive domains, we have only found attention/cognitive processing speed to have a more consistent positive association with sleep spindle activity. On the other hand, 8 studies investigated the relationship between sleep spindle and positive/negative symptom severity (n = 190), but findings were inconsistent. Spindle density is the most consistent parameter correlating with cognitive functions, while the best spindle parameter for correlating with positive and negative symptom severity cannot be identified due to mixed results.
This systematic review confirms the linkage between sleep spindle activity and cognitive functions. However, included studies had small sample sizes, with high risks of sampling and response bias. Moreover, confounders were often not controlled. The heterogeneous report of spindle parameters and use of cognitive assessment tools rendered meta-analysis infeasible. It is necessary to examine the longitudinal change of sleep spindle activity with the course of illness, as well as the effect of sleep spindle enhancing agents on cognitive function.
睡眠障碍与精神分裂症患者更差的认知和精神病性症状相关。越来越多的文献表明，精神分裂症患者的睡眠纺锤波缺陷可能是一种内表型，反映了丘脑 - 丘脑网状核 - 皮质回路功能失调。由于丘脑功能与认知、阳性和阴性症状相关，睡眠纺锤波活动有可能与这些症状相关。本系统评价的主要目的是评估精神病患者睡眠纺锤波活动与1）认知功能；以及2）阳性和阴性症状严重程度之间的关联。次要目的是研究哪个纺锤波参数是与认知功能以及阳性和阴性症状最一致的相关参数。
报告睡眠纺锤波活动与精神病性障碍患者认知功能、阳性和阴性症状之间关联的观察性研究被视为合格。我们制定了全面的电子检索策略，以识别在Pubmed、Embase、PsycINFO和CINAHL中经过同行评审的研究，涵盖截至2020年5月检索日期的所有文献，无语言限制。对已发表文章的参考文献进行手工检索以获取更多材料。联系已发表文章的作者获取更新或未发表的数据。通过横断面研究评估（AXIS）评估偏倚风险。
共选择了11项质量低至中等的横断面研究（n = 255）进行系统评价。其中8项研究探讨了睡眠纺锤波活动与认知功能之间的关联（n = 193），其中6项研究报告了正相关（仅4项研究报告了r值，范围为0.45至0.75）。在多个认知领域中，我们仅发现注意力/认知处理速度与睡眠纺锤波活动有更一致的正相关。另一方面，8项研究调查了睡眠纺锤波与阳性/阴性症状严重程度之间的关系（n = 190），但结果不一致。纺锤波密度是与认知功能最一致的参数，而由于结果不一，无法确定与阳性和阴性症状严重程度最相关的最佳纺锤波参数。
本系统评价证实了睡眠纺锤波活动与认知功能之间的联系。然而，纳入研究的样本量较小，存在抽样和应答偏倚的高风险。此外，混杂因素往往未得到控制。纺锤波参数的异质性报告以及认知评估工具的使用使得荟萃分析不可行。有必要研究睡眠纺锤波活动随病程的纵向变化，以及睡眠纺锤波增强剂对认知功能的影响。
