Identification of Distinct Psychosis Biotypes Using Brain-Based Biomarkers.
Identification of Distinct Psychosis Biotypes Using Brain-Based Biomarkers.
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DOI：
10.1176/appi.ajp.2015.14091200
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发表时间：
2016-04-01
期刊：
影响因子：
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通讯作者：
Tamminga CA
中科院分区：
文献类型：
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作者：
Clementz BA;Sweeney JA;Hamm JP;Ivleva EI;Ethridge LE;Pearlson GD;Keshavan MS;Tamminga CA
尽管有大量证据表明临床现象学方法无法完全捕捉到具有生物学意义的差异，但它仍然是对精神病进行分类的主要手段。本项目没有将临床诊断作为金标准，而是利用精神病病例之间的神经生物学异质性来描绘出独立于其现象学表现的亚组。
对患有精神分裂症、分裂情感性障碍和伴有精神病性症状的双相情感障碍的个体（N = 711）、他们的一级亲属（N = 883）以及在人口统计学上具有可比性的健康受试者（N = 278）收集了一个大型生物标志物组合（神经心理学、停止信号、眼跳控制和听觉刺激范式），这些范式表征了大脑功能的不同方面。利用不同范式之间的生物标志物差异创建了九个综合变量，用于捕捉精神病病例之间的神经生物学差异。还收集了关于外部验证指标（社会功能、结构磁共振成像、家族生物标志物和临床信息）的数据。
多变量分类分析确定了三种在神经生物学上不同的精神病生物型，它们不受临床诊断界限的限制。以临床《精神障碍诊断与统计手册》（DSM）诊断为标准的相同分析过程，最好用一个单一的严重程度连续体来描述（精神分裂症比分裂情感性障碍严重，分裂情感性障碍比双相精神病严重）；但生物型并非如此。与临床诊断相比，外部验证指标支持了这些亚组的独特性，突显了神经生物学分类方案相对于临床分类方案在区分精神病性障碍方面可能具有的优势。
这些数据说明了多种途径可能导致临床上相似的精神病表现，并且当把DSM诊断作为金标准时，它们为不同实验室在相同生物标志物变量上观察到的显著异质性提供了解释。
Clinical phenomenology remains the primary means for classifying psychoses despite considerable evidence that this method incompletely captures biologically meaningful differentiations. Rather than relying on clinical diagnoses as the gold standard, this project drew on neurobiological heterogeneity among psychosis cases to delineate subgroups independent of their phenomenological manifestations. A large biomarker panel (neuropsychological, stop signal, saccadic control, and auditory stimulation paradigms) characterizing diverse aspects of brain function was collected on individuals with schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis (N=711), their first-degree relatives (N=883), and demographically comparable healthy subjects (N=278). Biomarker variance across paradigms was exploited to create nine integrated variables that were used to capture neurobiological variance among the psychosis cases. Data on external validating measures (social functioning, structural magnetic resonance imaging, family biomarkers, and clinical information) were collected. Multivariate taxometric analyses identified three neurobiologically distinct psychosis biotypes that did not respect clinical diagnosis boundaries. The same analysis procedure using clinical DSM diagnoses as the criteria was best described by a single severity continuum (schizophrenia worse than schizoaffective disorder worse than bipolar psychosis); this was not the case for biotypes. The external validating measures supported the distinctiveness of these subgroups compared with clinical diagnosis, highlighting a possible advantage of neurobiological versus clinical categorization schemes for differentiating psychotic disorders. These data illustrate how multiple pathways may lead to clinically similar psychosis manifestations, and they provide explanations for the marked heterogeneity observed across laboratories on the same biomarker variables when DSM diagnoses are used as the gold standard.