Importance Although clinical criteria for identifying youth at risk for psychosis have been validated, they are not sufficiently accurate for predicting outcomes to inform major treatment decisions. The identification of biomarkers may improve outcome prediction among individuals at clinical high risk for psychosis (CHR-P). Objective To examine whether mismatch negativity (MMN) event-related potential amplitude, which is deficient in schizophrenia, is reduced in young people with the CHR-P syndrome and associated with outcomes, accounting for effects of antipsychotic medication use. Design, Setting, and Participants MMN data were collected as part of the multisite case-control North American Prodrome Longitudinal Study (NAPLS-2) from 8 university-based outpatient research programs. Baseline MMN data were collected from June 2009 through April 2013. Clinical outcomes were assessed throughout 24 months. Participants were individuals with the CHR-P syndrome and healthy controls with MMN data. Participants with the CHR-P syndrome who developed psychosis (ie, converters) were compared with those who did not develop psychosis (ie, nonconverters) who were followed up for 24 months. Analysis took place between December 2019 and December 2021. Main Outcomes and Measures Electroencephalography was recorded during a passive auditory oddball paradigm. MMN elicited by duration-, pitch-, and duration + pitch double-deviant tones was measured. Results The CHR-P group (n = 580; mean [SD] age, 19.24 [4.39] years) included 247 female individuals (42.6%) and the healthy control group (n = 241; mean age, 20.33 [4.74] years) included 114 female individuals (47.3%). In the CHR-P group, 450 (77.6%) were not taking antipsychotic medication at baseline. Baseline MMN amplitudes, irrespective of deviant type, were deficient in future CHR-P converters to psychosis (n = 77, unmedicated n = 54) compared with nonconverters (n = 238, unmedicated n = 190) in both the full sample (d = 0.27) and the unmedicated subsample (d = 0.33). In the full sample, baseline medication status interacted with group and deviant type indicating that double-deviant MMN, compared with single deviants, was reduced in unmedicated converters compared with nonconverters (d = 0.43). Further, within the unmedicated subsample, deficits in double-deviant MMN were most strongly associated with earlier conversion to psychosis (hazard ratio, 1.40 [95% CI, 1.03-1.90]; P = .03], which persisted over and above positive symptom severity. Conclusions and Relevance This study found that MMN amplitude deficits were sensitive to future psychosis conversion among individuals at risk of CHR-P, particularly those not taking antipsychotic medication at baseline, although associations were modest. While MMN shows limited promise as a biomarker of psychosis onset on its own, it may contribute novel risk information to multivariate prediction algorithms and serve as a translational neurophysiological target for novel treatment development in a subgroup of at-risk individuals.

中文翻译：

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精神病临床高风险青年对听觉偏差和未来精神病风险的不匹配消极反应。

重要性 尽管用于识别有精神病风险的青少年的临床标准已经得到验证，但它们不足以准确预测结果以告知主要治疗决策。生物标志物的鉴定可能会改善精神病临床高风险 (CHR-P) 个体的结果预测。目的 研究在患有 CHR-P 综合征的年轻人中，精神分裂症患者缺乏的错配阴性 (MMN) 事件相关电位振幅是否降低并与结果相关，从而解释抗精神病药物使用的影响。设计、设置和参与者 MMN 数据作为多中心病例对照北美前驱症状纵向研究 (NAPLS-2) 的一部分从 8 个基于大学的门诊研究项目中收集。从 2009 年 6 月到 2013 年 4 月收集了基线 MMN 数据。在整个 24 个月内评估了临床结果。参与者是患有 CHR-P 综合征的个体和具有 MMN 数据的健康对照。将发展为精神病（即转化者）的 CHR-P 综合征参与者与未发展为精神病（即未转化者）的参与者进行比较，并随访 24 个月。分析发生在 2019 年 12 月至 2021 年 12 月之间。在被动听觉古怪范式期间记录了主要结果和测量脑电图。测量了由持续时间、音高和持续时间 + 音高双异常音调引发的 MMN。结果 CHR-P 组（n = 580；平均 [SD] 年龄，19.24 [4.39] 岁）包括 247 名女性个体 (42.6%) 和健康对照组（n = 241；平均年龄，20.33 [4. 74] 岁）包括 114 名女性（47.3%）。在 CHR-P 组中，450 人 (77.6%) 在基线时未服用抗精神病药物。与非转化者（n = 238，未接受药物治疗的 n = 190）相比，在完整样本（d = 0.27) 和未用药子样本 (d = 0.33)。在完整样本中，基线药物治疗状态与群体和异常类型相互作用，表明与单一异常相比，未接受药物治疗的转化者与非转化者相比，双异常 MMN 减少 (d = 0.43)。此外，在未接受药物治疗的子样本中，双异常 MMN 的缺陷与早期转变为精神病的相关性最强（风险比，1.40 [95% CI，1.03-1.90]；P = .03，持续超过阳性症状的严重程度。结论和相关性 本研究发现，MMN 振幅缺陷对有 CHR-P 风险的个体未来的精神病转化敏感，尤其是那些在基线时未服用抗精神病药物的个体，尽管相关性不大。虽然 MMN 本身作为精神病发作的生物标志物显示出有限的前景，但它可能为多变量预测算法提供新的风险信息，并作为在高危个体亚组中开发新治疗方法的转化神经生理学目标。尽管协会是适度的。虽然 MMN 本身作为精神病发作的生物标志物显示出有限的前景，但它可能为多变量预测算法提供新的风险信息，并作为在高危个体亚组中开发新治疗方法的转化神经生理学目标。尽管协会是适度的。虽然 MMN 本身作为精神病发作的生物标志物显示出有限的前景，但它可能为多变量预测算法提供新的风险信息，并作为在高危个体亚组中开发新治疗方法的转化神经生理学目标。