University of California, San Francisco, California; San Francisco Veterans Administration Medical Center, San Francisco, California.
Yale University School of Medicine, New Haven, Connecticut.
Biol Psychiatry. 2014 Mar 15;75(6):459-69. doi: 10.1016/j.biopsych.2013.07.038. Epub 2013 Sep 16.
Only about one third of patients at high risk for psychosis based on current clinical criteria convert to a psychotic disorder within a 2.5-year follow-up period. Targeting clinical high-risk (CHR) individuals for preventive interventions could expose many to unnecessary treatments, underscoring the need to enhance predictive accuracy with nonclinical measures. Candidate measures include event-related potential components with established sensitivity to schizophrenia. Here, we examined the mismatch negativity (MMN) component of the event-related potential elicited automatically by auditory deviance in CHR and early illness schizophrenia (ESZ) patients. We also examined whether MMN predicted subsequent conversion to psychosis in CHR patients.
Mismatch negativity to auditory deviants (duration, frequency, and duration + frequency double deviant) was assessed in 44 healthy control subjects, 19 ESZ, and 38 CHR patients. Within CHR patients, 15 converters to psychosis were compared with 16 nonconverters with at least 12 months of clinical follow-up. Hierarchical Cox regression examined the ability of MMN to predict time to psychosis onset in CHR patients.
Irrespective of deviant type, MMN was significantly reduced in ESZ and CHR patients relative to healthy control subjects and in CHR converters relative to nonconverters. Mismatch negativity did not significantly differentiate ESZ and CHR patients. The duration + frequency double deviant MMN, but not the single deviant MMNs, significantly predicted the time to psychosis onset in CHR patients.
Neurophysiological mechanisms underlying automatic processing of auditory deviance, as reflected by the duration + frequency double deviant MMN, are compromised before psychosis onset and can enhance the prediction of psychosis risk among CHR patients.
根据目前的临床标准，只有约三分之一的处于精神病高危状态的患者在 2.5 年的随访期内转化为精神病障碍。针对临床高风险（CHR）个体进行预防干预可能会使许多人接受不必要的治疗，这突显了需要通过非临床措施来提高预测准确性。候选措施包括与精神分裂症具有既定敏感性的事件相关电位成分。在这里，我们研究了 CHR 和早期精神分裂症（ESZ）患者的听觉偏差自动诱发的事件相关电位中的失匹配负波（MMN）成分。我们还研究了 MMN 是否可以预测 CHR 患者随后是否会转化为精神病。
在 44 名健康对照者、19 名 ESZ 和 38 名 CHR 患者中评估了听觉偏差的 MMN（持续时间、频率和持续时间+频率双重偏差）。在 CHR 患者中，将 15 名转换为精神病的患者与至少 12 个月临床随访的 16 名未转换患者进行了比较。分层 Cox 回归检验了 MMN 在 CHR 患者中预测精神病发病时间的能力。
无论偏差类型如何，ESZ 和 CHR 患者的 MMN 均明显低于健康对照组，而 CHR 转换者的 MMN 明显低于未转换者。MMN 并未显著区分 ESZ 和 CHR 患者。持续时间+频率双重偏差 MMN 但不是单一偏差 MMN 显著预测了 CHR 患者的精神病发病时间。
在精神病发作之前，反映在持续时间+频率双重偏差 MMN 中的听觉偏差自动处理的神经生理机制受损，并且可以提高 CHR 患者的精神病风险预测。
