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：B-SNIP 联盟的复制和验证


目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，也不允许基于神经生物学的个体化治疗处方。在本报告中，我们研究了两个大样本的精神分裂症、分裂情感性和伴有精神病的双相情感障碍病例，其临床特征为幻觉、妄想、思维障碍、情感或阴性症状。对精神病病例进行亚型分类的生物标志物方法（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 个个体生物标记物取自一般认知 (BACS)、运动抑制（停止信号） ）、眼跳系统（支持眼跳和反眼跳）以及精神病相关脑功能的听觉 EEG/ERP（配对刺激和奇怪）任务是可复制的（r 值从 .96–.99 ）并且在时间上稳定（r 值从 .96 到 .99）。 76–.95）。使用数字分类法（k 均值聚类）和九组综合生物标志物特征（称为生物因子）产生了三个生物型，这两个样本之间几乎相同，并且基于交叉验证显示出高度相似的病例分配给亚组（88.5％– 89%）。 Biotype-1 和-2 的认知能力都很差。 Biotype-1 的进一步特征是神经反应幅度较低，而 Biotype-2 的进一步特征是神经反应过度活跃和感觉运动抑制较差。 Biotype-3 的所有生物因子几乎正常。 使用内在神经活动和听觉稳态刺激的测量对 Biotype EEG/ERP 神经生理学进行构建验证，强调了这些结果的稳健性。精神病生物型可能会为治疗和病因学研究产生有意义的神经生物学目标。