Delirium is a clinical syndrome occurring in heterogeneous patient populations. It affects 45–87% of critical care patients and is often associated with adverse outcomes including acquired dementia, institutionalisation, and death. Despite an exponential increase in delirium research in recent years, the pathophysiological mechanisms resulting in the clinical presentation of delirium are still hypotheses. Efforts have been made to categorise the delirium spectrum into clinically meaningful subgroups (subphenotypes), using psychomotor subtypes such as hypoactive, hyperactive, and mixed, for example, and also inflammatory and non-inflammatory delirium. Delirium remains, however, a constellation of symptoms resulting from a variety of risk factors and precipitants with currently no successful targeted pharmacological treatment. Identifying specific clinical and biological subphenotypes will greatly improve understanding of the relationship between the clinical symptoms and the putative pathways and thus risk factors, precipitants, natural history, and biological mechanism. This will facilitate risk factor mitigation, identification of potential methods for interventional studies, and informed patient and family counselling. Here, we review evidence to date and propose a framework to identify subphenotypes. Endotype identification may be done by clustering symptoms with their biological mechanism, which will facilitate research of targeted treatments. In order to achieve identification of delirium subphenotypes, the following steps must be taken: (1) robust records of symptoms must be kept at a clinical level. (2) Global collaboration must facilitate large, heterogeneous research cohorts. (3) Patients must be clustered for identification, validation, and mapping of subphenotype stability.

中文翻译：

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谵妄的表型和亚表型：对当前分类和进展建议的回顾

谵妄是一种发生在异质患者群体中的临床综合征。它影响了 45-87% 的重症监护患者，并且通常与不良后果有关，包括获得性痴呆、住院治疗和死亡。尽管近年来谵妄研究呈指数增长，但导致谵妄临床表现的病理生理机制仍是假设。已经努力将谵妄谱分类为具有临床意义的亚组（亚表型），使用精神运动亚型，例如活动不足、活动过度和混合，以及炎症性和非炎症性谵妄。然而，谵妄仍然是由各种风险因素和诱发因素引起的一系列症状，目前还没有成功的靶向药物治疗。识别特定的临床和生物学亚表型将大大提高对临床症状与假定途径之间关系的理解，从而提高对风险因素、沉淀物、自然史和生物学机制的理解。这将有助于减轻风险因素，确定介入研究的潜在方法，并为患者和家庭提供知情咨询。在这里，我们回顾了迄今为止的证据并提出了一个识别亚表型的框架。内型鉴定可以通过将症状与其生物学机制聚类来完成，这将有助于靶向治疗的研究。为了识别谵妄亚型，必须采取以下步骤： (1) 必须在临床水平上保留可靠的症状记录。(2) 全球合作必须促进大规模、异质研究队列。(3) 必须对患者进行聚类以进行亚表型稳定性的鉴定、验证和作图。