Embracing the Complexity of Heterogeneity in Schizophrenia: A New Perspective From Latent Clinical-Anatomical Dimensions.
Embracing the Complexity of Heterogeneity in Schizophrenia: A New Perspective From Latent Clinical-Anatomical Dimensions.
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拥抱精神分裂症异质性的复杂性：潜在临床解剖维度的新视角。
DOI：
10.1093/schbul/sbaa122
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发表时间：
2020
影响因子：
6.6
通讯作者：
Mittal,VijayA
中科院分区：
文献类型：
--
作者：
Gratton,Caterina;Mittal,VijayA
越来越多的人支持这样一种观点，即精神分裂症，正如我们所知，不是一种离散的疾病，而是大脑功能障碍的普遍症状。不同的个体群体，共享一些共同的症状，可能会受到不同的潜在病理生理学的影响。这一想法是由许多因素驱动的，包括临床观察结果表明患者现象学、病程、人口统计学和预后存在广泛差异（例如，缺陷综合征1）。进一步的支持来自一系列新的研究，这些研究采用了无监督的机器学习方法，并产生了令人信服的证据，表明生物学和临床相关的离散生物型2以及临床高风险（HRR）亚型。[3]当然，如上所述，精神分裂症中有一些共同的症状表型，与任何亚组无关，并且有一个合理的论点可以证明，这些症状表型是诊断系统和临床经验交流的核心。在精神病中也广泛观察到一系列大脑异常，这些异常在多大程度上映射到特定的症状或功能，或引起更广泛的临床特征，仍然是一个悬而未决的问题。这些发现也可能与代偿机制或将精神分裂症与神经型对照区分开来的任何混淆有关。目前尚不清楚特定的大脑异常是否有助于特定的亚型，或反映或有助于跨越精神分裂症谱的维度。事实是，这一切都非常复杂，而且这些可能性并不相互排斥;在所有的可能性中，每一个都可能是正确的和揭示的。但是，我们如何才能接受这种复杂性并向前迈进呢？作为一个领域，我们继续受到现有工具和方法的限制。例如，虽然生物分型有许多好处，但它以牺牲任何共享的症状和组件（机制）为代价强制离散的类别，这些症状和组件（机制）在各个亚组中维度上运行。从本质上讲，虽然这种方法具有巨大的潜力，
Support continues to grow for the idea that schizophrenia, as we know it, is not a discrete illness but rather a generalized symptom of brain dysfunction. Distinct groups of individuals, sharing some common symptoms, may be affected by different underlying pathophysiology. This idea is driven by a number of factors, including clinical observations suggesting a wide variation in patient phenomenology, course, demographics, and prognosis (eg, deficit syndrome 1). Further support comes from a series of new studies that have adopted unsupervised machine learning approaches and generated compelling evidence to suggest biological and clinically relevant discrete biotypes 2 as well as clinical high-risk (CHR) subtypes. 3 Of course, as noted above, there are common symptom phenotypes across schizophrenia, irrespective of any subgroups, and there is a reasonable argument to be made that these are central to diagnostic systems and in communicating the clinical experience. A range of brain abnormalities is also widely observed in psychosis, and the extent to which these map on to specific symptoms or functions, or give rise to broader constellations of clinical features, remains an open question. Clouding this picture, findings may also relate to compensatory mechanisms or to any number of confounds that separate schizophrenia from neurotypical controls. It is presently unclear whether particular brain abnormalities contribute to particular subtypes, or reflect or contribute to dimensions that cut across the schizophrenia spectrum. The truth is that this is all very complicated and that these possibilities are not mutually exclusive; in all likelihood each is probably correct and revealing. But how then can we embrace this complexity and move forward?As a field, we have continued to be limited by our available tools and approaches. For example, while biotyping has many benefits, it forces discrete categories at the expense of any shared symptoms and components (mechanisms) that run dimensionally across subgroups. Essentially, while this method holds enormous potential for promoting