Mathalon Daniel H, Nicholas Spero, Roach Brian J, Billah Tashrif, Lavoie Suzie, Whitford Thomas, Hamilton Holly K, Addamo Lauren, Anohkin Andrey, Bekinschtein Tristan, Belger Aysenil, Buccilli Kate, Cahill John, Carrión Ricardo E, Damiani Stefano, Dzafic Ilvana, Ebdrup Bjørn H, Izyurov Igor, Jarcho Johanna, Jenni Raoul, Jo Anna, Kerins Sarah, Lee Clarice, Martin Elizabeth A, Mayol-Troncoso Rocio, Niznikiewicz Margaret A, Parvaz Muhammad, Pogarell Oliver, Prieto-Montalvo Julio, Rabin Rachel, Roalf David R, Rogers Jack, Salisbury Dean F, Shaik Riaz, Shankman Stewart, Stevens Michael C, Suen Yi Nam, Swann Nicole C, Tang Xiaochen, Thompson Judy L, Tso Ivy, Wenzel Julian, Zhou Juan Helen, Addington Jean, Alameda Luis, Arango Celso, Breitborde Nicholas J K, Broome Matthew R, Cadenhead Kristin S, Calkins Monica E, Castillo-Passi Rolando I, Chen Eric Yu Hai, Choi Jimmy, Conus Philippe, Corcoran Cheryl M, Cornblatt Barbara A, Diaz-Caneja Covadonga M, Ellman Lauren M, Fusar-Poli Paolo, Gaspar Pablo A, Gerber Carla, Glenthøj Louise Birkedal, Horton Leslie E, Hui Christy Lai Ming, Kambeitz Joseph, Kambeitz-Ilankovic Lana, Keshavan Matcheri S, Kim Minah, Kim Sung-Wan, Koutsouleris Nikolaos, Kwon Jun Soo, Langbein Kerstin, Mamah Daniel, Mittal Vijay A, Nordentoft Merete, Pearlson Godfrey D, Perez Jesus, Perkins Diana O, Powers Albert R, Sabb Fred W, Schiffman Jason, Shah Jai L, Silverstein Steven M, Smesny Stefan, Stone William S, Strauss Gregory P, Upthegrove Rachel, Verma Swapna K, Wang Jijun, Wolf Daniel H, Zhang Tianhong, Bouix Sylvain, Pasternak Ofer, Cho Kang-Ik K, Coleman Michael J, Dwyer Dominic, Nunez Angela, Tamayo Zailyn, Wood Stephen J, Kahn Rene S, Kane John M, McGorry Patrick D, Bearden Carrie E, Nelson Barnaby, Woods Scott W, Shenton Martha E, Light Gregory A
Department of Psychiatry and Behavioral Sciences and Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
Mental Health Service, Veterans Affairs San Francisco Health Care System, San Francisco, CA, USA.
Schizophrenia (Heidelb). 2025 Jun 6;11(1):85. doi: 10.1038/s41537-025-00622-0.
Individuals at clinical high risk for psychosis (CHR) have variable clinical outcomes and low conversion rates, limiting development of novel and personalized treatments. Moreover, given risks of antipsychotic drugs, safer effective medications for CHR individuals are needed. The Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ) Program was launched to address this need. Based on past CHR and schizophrenia studies, AMP SCZ assessed electroencephalography (EEG)-based event-related potential (ERP), event-related oscillation (ERO), and resting EEG power spectral density (PSD) measures, including mismatch negativity (MMN), auditory and visual P300 to target (P3b) and novel (P3a) stimuli, 40-Hz auditory steady state response, and resting EEG PSD for traditional frequency bands (eyes open/closed). Here, in an interim analysis of AMP SCZ EEG measures, we assess test-retest reliability and stability over sessions (baseline, month-2 follow-up) in CHR (n = 654) and community control (CON; n = 87) participants. Reliability was calculated as Generalizability (G)-coefficients, and changes over session were assessed with paired t-tests. G-coefficients were generally good to excellent in both groups (CHR: mean = 0.72, range = 0.49-0.85; CON: mean = 0.71, range = 0.44-0.89). Measure magnitudes significantly (p < 0.001) decreased over session (MMN, auditory and visual target P3b, visual novel P3a, 40-Hz ASSR) and/or over runs within sessions (MMN, auditory/visual novel P3a and target P3b), consistent with habituation effects. Despite these small systematic habituation effects, test-retest reliabilities of the AMP SCZ EEG-based measures are sufficiently strong to support their use in CHR studies as potential predictors of clinical outcomes, markers of illness progression, and/or target engagement or secondary outcome measures in controlled clinical trials.
临床高危精神病个体（CHR）的临床结局各异且转化率低，这限制了新型个性化治疗方法的开发。此外，鉴于抗精神病药物的风险，需要为CHR个体提供更安全有效的药物。加速药物合作组织精神分裂症（AMP® SCZ）项目正是为满足这一需求而启动的。基于以往对CHR和精神分裂症的研究，AMP SCZ评估了基于脑电图（EEG）的事件相关电位（ERP）、事件相关振荡（ERO）以及静息EEG功率谱密度（PSD）测量指标，包括失配负波（MMN）、对目标（P3b）和新异（P3a）刺激的听觉及视觉P300、40赫兹听觉稳态反应以及传统频段（睁眼/闭眼）的静息EEG PSD。在此，在对AMP SCZ EEG测量指标的中期分析中，我们评估了CHR组（n = 654）和社区对照组（CON；n = 87）参与者在各次测量（基线、2个月随访）间的重测信度和稳定性。信度以概化系数（G系数）计算，各次测量间的变化通过配对t检验进行评估。两组的G系数总体良好至优秀（CHR组：均值 = 0.72，范围 = 0.49 - 0.85；CON组：均值 = 0.71，范围 = 0.44 - 0.89）。测量幅度在各次测量间（MMN、听觉和视觉目标P3b、视觉新异P3a、40赫兹听觉稳态反应）和/或各次测量内（MMN、听觉/视觉新异P3a和目标P3b）显著降低（p < 0.001），这与习惯化效应一致。尽管存在这些微小的系统性习惯化效应，但基于AMP SCZ EEG的测量指标的重测信度足够高，足以支持其在CHR研究中作为临床结局的潜在预测指标、疾病进展的标志物以及/或者在对照临床试验中作为靶点参与度或次要结局指标使用。
