Current clinical phenomenological diagnosis in psychiatry neither captures biologically homologous disease entities nor allows for individualized treatment prescriptions based on neurobiology. In this report, we studied two large samples of cases with schizophrenia, schizoaffective, and bipolar I disorder with psychosis, presentations with clinical features of hallucinations, delusions, thought disorder, affective, or negative symptoms. A biomarker approach to subtyping psychosis cases (called psychosis Biotypes) captured neurobiological homology that was missed by conventional clinical diagnoses. Two samples (called “B-SNIP1” with 711 psychosis and 274 healthy persons, and the “replication sample” with 717 psychosis and 198 healthy persons) showed that 44 individual biomarkers, drawn from general cognition (BACS), motor inhibitory (stop signal), saccadic system (pro- and anti-saccades), and auditory EEG/ERP (paired-stimuli and oddball) tasks of psychosis-relevant brain functions were replicable (r’s from .96–.99) and temporally stable (r’s from .76–.95). Using numerical taxonomy (k-means clustering) with nine groups of integrated biomarker characteristics (called bio-factors) yielded three Biotypes that were virtually identical between the two samples and showed highly similar case assignments to subgroups based on cross-validations (88.5%–89%). Biotypes-1 and -2 shared poor cognition. Biotype-1 was further characterized by low neural response magnitudes, while Biotype-2 was further characterized by overactive neural responses and poor sensory motor inhibition. Biotype-3 was nearly normal on all bio-factors. Construct validation of Biotype EEG/ERP neurophysiology using measures of intrinsic neural activity and auditory steady state stimulation highlighted the robustness of these outcomes. Psychosis Biotypes may yield meaningful neurobiological targets for treatments and etiological investigations.

中文翻译：

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精神病生物型：来自 B-SNIP 联盟的复制和验证

当前精神病学的临床现象学诊断既不能捕获生物学上同源的疾病实体，也不能基于神经生物学制定个体化治疗处方。在这份报告中，我们研究了两个大样本的精神分裂症、情感分裂症和 I 型双相情感障碍伴精神病病例，其临床表现包括幻觉、妄想、思维障碍、情感或阴性症状。一种对精神病病例进行分型的生物标志物方法（称为精神病生物型）捕获了传统临床诊断所遗漏的神经生物学同源性。两个样本（称为“B-SNIP1”，包含 711 名精神病患者和 274 名健康人，以及“复制样本”，包含 717 名精神病患者和 198 名健康人）显示，44 种个体生物标志物来自一般认知 (BACS)、运动抑制（停止信号） ), 精神病相关脑功能的扫视系统（支持和反扫视）和听觉 EEG/ERP（配对刺激和古怪）任务是可复制的（r 从 .96–0.99）和暂时稳定的（r 从 .76– .95）。使用具有九组综合生物标志物特征（称为生物因子）的数值分类法（k 均值聚类）产生了三个生物型，它们在两个样本之间几乎相同，并且显示基于交叉验证（88.5％- 89%）。Biotypes-1 和-2 的认知能力都很差。Biotype-1 的进一步特征是低神经反应幅度，而 Biotype-2 的进一步特征是过度活跃的神经反应和较差的感觉运动抑制。Biotype-3 在所有生物因素上几乎正常。使用内在神经活动和听觉稳态刺激的措施构建生物型脑电图/ERP 神经生理学验证突出了这些结果的稳健性。精神病生物型可能会产生有意义的神经生物学目标，用于治疗和病因学调查。