Why has it taken so long for biological psychiatry to develop clinical tests and what to do about it?
Why has it taken so long for biological psychiatry to develop clinical tests and what to do about it?
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DOI：
10.1038/mp.2012.105
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发表时间：
2012-12-01
影响因子：
11
通讯作者：
Insel, T. R.
中科院分区：
文献类型：
--
作者：
Kapur, S.;Phillips, A. G.;Insel, T. R.
精神障碍患者表现出许多与正常人不同的生理异常；然而，其中很少有临床应用的试验。造成这种延迟的原因有以下几个：缺乏对精神疾病的生物学“黄金标准”定义；大量具有统计学意义，但差异极小的生物学发现；以一种既不证实也不反驳这些发现的方式近似地重复这些发现；重点是将原型患者与健康对照进行比较，从而产生临床适用性有限的区分。克服这些障碍需要一种新的方法。与其寻求能够“诊断”dsm定义的疾病的生物医学测试，该领域应该专注于识别跨越表型诊断的生物学同质亚型，从而避开黄金标准的问题。为了确保临床相关性和适用性，该领域需要关注相关临床人群之间有临床意义的差异，而不是假设排斥与正常对照。验证这些新的生物标志物定义的亚型将需要纵向研究与标准化的措施，可以在研究之间共享和比较，从而克服显著性追逐和近似重复的问题。这样的生物学测试，以及它们定义的亚型，将为“分层精神病学”提供一个自然的基础，这将改善跨越传统诊断界限的临床结果。
Patients with mental disorders show many biological abnormalities which distinguish them from normal volunteers; however, few of these have led to tests with clinical utility. Several reasons contribute to this delay: lack of a biological 'gold standard' definition of psychiatric illnesses; a profusion of statistically significant, but minimally differentiating, biological findings; approximate replications' of these findings in a way that neither confirms nor refutes them; and a focus on comparing prototypical patients to healthy controls which generates differentiations with limited clinical applicability. Overcoming these hurdles will require a new approach. Rather than seek biomedical tests that can 'diagnose' DSM-defined disorders, the field should focus on identifying biologically homogenous subtypes that cut across phenotypic diagnosis-thereby sidestepping the issue of a gold standard. To ensure clinical relevance and applicability, the field needs to focus on clinically meaningful differences between relevant clinical populations, rather than hypothesis-rejection versus normal controls. Validating these new biomarker-defined subtypes will require longitudinal studies with standardized measures which can be shared and compared across studies-thereby overcoming the problem of significance chasing and approximate replications. Such biological tests, and the subtypes they define, will provide a natural basis for a 'stratified psychiatry' that will improve clinical outcomes across conventional diagnostic boundaries.