Insomnia disorder subtypes derived from life history and traits of affect and personality
Insomnia disorder subtypes derived from life history and traits of affect and personality
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DOI：
10.1016/s2215-0366(18)30464-4
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发表时间：
2019-02-01
影响因子：
64.3
通讯作者：
Van Someren, Eus J. W.
中科院分区：
文献类型：
--
作者：
Blanken, Tessa F.;Benjamins, Jeroen S.;Van Someren, Eus J. W.
背景失眠症是第二常见的精神疾病，也是抑郁症的主要危险因素。失眠症患者的临床和生物标志物发现不一致，表明存在异质性，这种疾病的亚型仍未得到识别。以前在疾病分类学中自上而下提出的亚型已经不够有效。在这项大规模的研究中，我们的目的是通过对一组多维度的生物学特征进行数据驱动分析，揭示失眠症的强大亚型。方法在这一系列研究中，我们从荷兰睡眠登记处招募了参与者，这是一个年龄在18岁或以上的志愿者数据库，我们在线跟踪调查了他们的特征，睡眠，生活事件，和健康史与34个选定的问卷，其中参与者完成至少一个。我们通过潜在类别分析确定了失眠症的亚型。我们通过使用第二个非重叠队列来评估我们确定的失眠症亚型的价值，这些队列是通过电子邮件发送给荷兰睡眠登记处参与者的新样本的时事通讯招募的，并通过评估几年随访的受试者内稳定性。我们广泛测试了这些亚型对睡眠主诉、合并症（包括抑郁症）和苯二氮卓类药物反应的临床有效性;在两种失眠症亚型中，我们还通过使用脑电图生物标志物和认知行为治疗的有效性评估了这些亚型的临床相关性。为了便于实施，我们随后构建了一个简洁的亚型问卷，我们验证了这份问卷在第二个，非重叠cohol.Findings 4322荷兰睡眠登记参与者完成了至少一个选定的问卷，人口统计学问卷，并评估他们的失眠严重程度指数（ISI）之间的2010年3月2日，2016年10月28日。2224名（51%）参与者可能患有失眠症，定义为ISI评分至少为10分，2098名（49%）ISI评分较低的参与者作为对照组。通过对2224名参与者的问卷调查进行潜在类别分析，我们确定了五种新的失眠症亚型：高度苦恼，中度苦恼但对奖励敏感（即对愉快情绪的反应完整），中度苦恼和奖励不敏感，轻度苦恼与高反应（对环境和生活事件），以及轻度苦恼与低反应。在2017年6月12日至2017年11月26日期间评估的251名新参与者的第二个非重叠重复样本中，也确定了五种亚型是最佳的。在发育样本和复制样本中，每个参与者都被归类为只有一个亚型，后验概率高（0.91-1.00）。在4.8年（SD 1.6）后（2017年4月13日至2017年6月21日）重新评估的2224名失眠参与者的原始样本中，215人保持原始亚型的概率为0.87，表明分类的稳定性很高。我们发现了所识别的亚型之间在发育轨迹、对治疗的反应、脑电图生物标志物的存在以及抑郁症的风险方面的差异，这些差异在组间高达5倍，这表明这些亚型具有临床相关性。解释失眠症患者的高维数据驱动亚型已经解决了未满足的需求，以减少失眠症的异质性。分型有助于识别失眠的根本原因，开发个性化治疗，并选择抑郁风险最高的患者纳入预防抑郁症的试验。版权所有（C）2019 Elsevier Ltd.保留所有权利。
Background Insomnia disorder is the second most prevalent mental disorder, and it is a primary risk factor for depression. Inconsistent clinical and biomarker findings in patients with insomnia disorder suggest that heterogeneity exists and that subtypes of this disease remain unrecognised. Previous top-down proposed subtypes in nosologies have had insufficient validity. In this large-scale study, we aimed to reveal robust subtypes of insomnia disorder by use of data-driven analyses on a multidimensional set of biologically based traits.Methods In this series of studies, we recruited participants from the Netherlands Sleep Registry, a database of volunteers aged 18 years or older, who we followed up online to survey traits, sleep, life events, and health history with 34 selected questionnaires of which participants completed at least one. We identified insomnia disorder subtypes by use of latent class analyses. We evaluated the value of our identified subtypes of insomnia disorder by use of a second, non-overlapping cohort who were recruited through a newsletter that was emailed to a new sample of Netherlands Sleep Registry participants, and by assessment of within-subject stability over several years of follow-up. We extensively tested the clinical validity of these subtypes for the development of sleep complaints, comorbidities (including depression), and response to benzodiazepines; in two subtypes of insomnia disorder, we also assessed the clinical relevance of these subtypes by use of an electroencephalogram biomarker and the effectiveness of cognitive behavioural therapy. To facilitate implementation, we subsequently constructed a concise subtype questionnaire and we validated this questionnaire in the second, non-overlapping cohort.Findings 4322 Netherlands Sleep Registry participants completed at least one of the selected questionnaires, a demographic questionnaire, and an assessment of their Insomnia Severity Index (ISI) between March 2, 2010, and Oct 28, 2016. 2224 (51%) participants had probable insomnia disorder, defined as an ISI score of at least 10, and 2098 (49%) participants with a lower ISI score served as a control group. With a latent class analysis of the questionnaire responses of 2224 participants, we identified five novel insomnia disorder subtypes: highly distressed, moderately distressed but reward sensitive (ie, with intact responses to pleasurable emotions), moderately distressed and reward insensitive, slightly distressed with high reactivity (to their environment and life events), and slightly distressed with low reactivity. In a second, non-overlapping replication sample of 251 new participants who were assessed between June 12, 2017, and Nov 26, 2017, five subtypes were also identified to be optimal. In both the development sample and replication sample, each participant was classified as having only one subtype with high posterior probability (0.91-1.00). In 215 of the original sample of 2224 participants with insomnia who were reassessed 4.8 (SD 1.6) years later (between April 13, 2017, and June 21, 2017), the probability of maintaining their original subtype was 0.87, indicating a high stability of the classification. We found differences between the identified subtypes in developmental trajectories, response to treatment, the presence of an electroencephalogram biomarker, and the risk of depression that was up to five times different between groups, which indicated a clinical relevance of these subtypes.Interpretation High-dimensional data-driven subtyping of people with insomnia has addressed an unmet need to reduce the heterogeneity of insomnia disorder. Subtyping facilitates identification of the underlying causes of insomnia, development of personalised treatments, and selection of patients with the highest risk of depression for inclusion in trials regarding prevention of depression. Copyright (C) 2019 Elsevier Ltd. All rights reserved.