Hamilton Holly K, Boos Alison K, Mathalon Daniel H
San Francisco Veterans Affairs Health Care System, San Francisco, California; Department of Psychiatry, University of California, San Francisco, California.
San Francisco Veterans Affairs Health Care System, San Francisco, California; Northern California Institute for Research and Education, San Francisco, California.
Biol Psychiatry. 2020 Aug 15;88(4):294-303. doi: 10.1016/j.biopsych.2020.04.002. Epub 2020 Apr 14.
Clinical outcomes vary among youths at clinical high risk for psychosis (CHR-P), with approximately 20% progressing to full-blown psychosis over 2 to 3 years and 30% achieving remission. Recent research efforts have focused on identifying biomarkers that precede psychosis onset and enhance the accuracy of clinical outcome prediction in CHR-P individuals, with the ultimate goal of developing staged treatment approaches based on the individual's level of risk. Identifying such biomarkers may also facilitate progress toward understanding pathogenic mechanisms underlying psychosis onset, which may support the development of mechanistically informed early interventions for psychosis. In recent years, electroencephalography-based event-related potential measures with established sensitivity to schizophrenia have gained traction in the study of CHR-P and its clinical outcomes. In this review, we describe the evidence for event-related potential abnormalities in CHR-P and discuss how they inform our understanding of information processing deficits as vulnerability markers for emerging psychosis and as indicators of future outcomes. Among the measures studied, P300 and mismatch negativity are notable because deficits predict conversion to psychosis and/or CHR-P remission. However, the accuracy with which these and other measures predict outcomes in CHR-P has been obscured in the prior literature by the tendency to only report group-level differences, underscoring the need for inclusion of individual predictive accuracy metrics in future studies. Nevertheless, both P300 and mismatch negativity show promise as electrophysiological markers of risk for psychosis, as target engagement measures for clinical trials, and as potential translational bridges between human studies and animal models focused on novel drug development for early psychosis.
临床高危精神病青年（CHR-P）的临床结局各不相同，约20%的人在2至3年内发展为全面性精神病，30%的人实现缓解。最近的研究工作集中在识别精神病发作前的生物标志物，并提高CHR-P个体临床结局预测的准确性，其最终目标是根据个体的风险水平制定分阶段治疗方法。识别此类生物标志物还可能有助于在理解精神病发作的致病机制方面取得进展，这可能支持开发基于机制的精神病早期干预措施。近年来，基于脑电图的事件相关电位测量方法对精神分裂症具有既定的敏感性，在CHR-P及其临床结局的研究中受到了关注。在这篇综述中，我们描述了CHR-P中事件相关电位异常的证据，并讨论了它们如何增进我们对信息处理缺陷的理解，这些缺陷是新兴精神病的易感性标志物和未来结局的指标。在所研究的测量方法中，P300和失配负波值得注意，因为这些缺陷可预测向精神病的转化和/或CHR-P的缓解。然而，在先前的文献中，这些测量方法和其他测量方法预测CHR-P结局的准确性因仅报告组间差异的倾向而被掩盖，这突出了在未来研究中纳入个体预测准确性指标的必要性。尽管如此，P300和失配负波都有望作为精神病风险的电生理标志物、临床试验的靶点参与测量方法，以及作为人类研究与专注于早期精神病新药开发的动物模型之间的潜在转化桥梁。
