The electroencephalography protocol for the Accelerating Medicines Partnership® Schizophrenia Program: Reliability and stability of measures

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.

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Journal
Schizophrenia
Published
2025-06-06
DOI
https://doi.org/10.1038/s41537-025-00622-0
Citations
4
Primary Topic
Neural dynamics and brain function
Type
article
Field-Weighted Citation Impact
5.72

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article

The electroencephalography protocol for the Accelerating Medicines Partnership® Schizophrenia Program: Reliability and stability of measures

Matcheri S. Keshavan, Rocío Mayol-Troncoso, Sylvain Bouix, Muhammad A. Parvaz et al.
4 citations
Schizophrenia
Neural dynamics and brain function
5.72
article

The electroencephalography protocol for the Accelerating Medicines Partnership® Schizophrenia Program: Reliability and stability of measures

Matcheri S. Keshavan, Rocío Mayol-Troncoso, Sylvain Bouix, Muhammad A. Parvaz, Celso Arango, Barbara A. Cornblatt, John M. Kane, Oliver Pogarell, Raoul Jenni, Diana O. Perkins, Jai L. Shah, Holly Hamilton, Albert R. Powers, Stewart A. Shankman, Godfrey D. Pearlson, Dean F. Salisbury, Carrie E. Bearden, Fred W. Sabb, Kerstin Langbein, Nicholas J. K. Breitborde, Jason Eric Schiffman, Johanna M. Jarcho, Gregory P. Strauss, Jijun Wang, Philippe Conus, Daniel H. Mathalon, Luis Alameda, Brian J. Roach, Swapna Verma, Lana Kambeitz‐Ilankovic, Jun Soo Kwon, Stephen James Wood, Dominic Dwyer, Suzie Lavoie, René S. Kahn, Tashrif Billah, Matthew R. Broome, Juan Helen Zhou, Julian Wenzel, Covadonga M. Díaz‐Caneja, Merete Nordentoft, Andrey Anohkin, Minah Kim, Clarice Lee, Steven M. Silverstein, Carla Gerber, David R. Roalf, Ofer Pasternak, Ricardo E. Carrión, Michael C. Stevens, Rachel A. Rabin, Christy Lai Ming Hui, Barnaby Nelson, Pablo A. Gaspar, Judy L. Thompson, Jean Addington, Cheryl M. Corcoran, Jesús Pérez, Ilvana Dzafic, John D. Cahill, Rachel Upthegrove, William S. Stone, XiaoChen Tang, Patrick D. McGorry, Sarah Kerins, Nicole C. Swann, Paolo Fusar‐Poli, Stefano Damiani, Riaz Shaik, Yi Nam Suen, Zailyn Tamayo, Monica E. Calkins, Kate Buccilli, Anna Jo, Rolando I Castillo-Passi, Scott W. Woods, Jack D. Rogers, Bjørn Hylsebeck Ebdrup, Ivy F. Tso, Margaret Niznikiewicz, Stefan Smesny, Kristin S. Cadenhead, Ayşenil Belger, Martha E. Shenton, Daniel H. Wolf, Igor Izyurov, Joseph Kambeitz, Spero Nicholas, Vijay Anand Mittal, Leslie E. Horton, Thomas J. Whitford, Tristán Bekinschtein, Nikolaos Koutsouleris, Lauren Addamo, Kang Ik K. Cho, Sung‐Wan Kim, Tianhong Zhang, Eric Yu Hai Chen, Elizabeth A. Martin, Jimmy Choi, Louise Birkedal Glenthøj, Michael J. Coleman, Juan Montalvo, Ángela Núñez, Lauren M. Ellman
article en
4 citations

Abstract

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.

SchizophreniaVol. 11(1)
Chonnam National University (KR), Northwestern University (US), University of North Carolina at Chapel Hill (US), University of Copenhagen (DK), Brigham and Women's Hospital (US), Hartford Hospital (US), University of Minnesota (US), Northwell Health (US), Beth Israel Deaconess Medical Center (US), Oregon Research Institute (US), Feinstein Institute for Medical Research (US), Universidad del Desarrollo (CL), Harvard University (US), Seoul National University (KR), University of California, Los Angeles (US), University of Georgia (US), The University of Melbourne (AU), National University of Singapore (SG), University of Calgary (CA), University of Pittsburgh (US), Douglas College (CA), University of California, San Francisco (US), University of Cologne (DE), University of Oregon (US), King's College London (GB), Universidad de Salamanca (ES), University of California, Irvine (US), Washington University in St. Louis (US), University of Cambridge (GB), University of Pavia (IT), Instituto de Salud Carlos III (ES), Clínica Alemana (CL), Glostrup Hospital (DK), Shanghai Mental Health Center (CN), Seoul National University Hospital (KR), The Ohio State University Wexner Medical Center (US), University of Rochester Medical Center (US), Hospital General Universitario Gregorio Marañón (ES), Alberto Hurtado University (CL), UNSW Sydney (AU), Yale University (US), University of California San Diego (US), University of Oxford (GB), Massachusetts General Hospital (US), Centro de Investigación Biomédica en Red de Salud Mental (ES), Donald & Barbara Zucker School of Medicine at Hofstra/Northwell (US), Orygen (AU), Boston VA Research Institute (US), King's College School (GB), Duke-NUS Medical School (SG), Instituto de Investigación Biomédica de Salamanca (ES), Jena University Hospital (DE), Behavioral Health Network (US), Institute of Mental Health (SG), Hanyang University Seoul Hospital (KR), San Francisco VA Health Care System (US), Cambridgeshire and Peterborough NHS Foundation Trust (GB), Department of Behavioral Health and Intellectual Disability Services (US), University Hospital Cologne (DE), Birmingham Women’s and Children’s NHS Foundation Trust (GB), Connecticut Mental Health Center (US), Northern California Institute for Research and Education (US), Hotchkiss Brain Institute (CA), McGill University (CA), University of Chile (CL), University of Pennsylvania (US), University of Birmingham (GB), Ludwig-Maximilians-Universität München (DE), Temple University (US), University of Hong Kong (HK), École de Technologie Supérieure (CA), University of Lausanne (CH), Icahn School of Medicine at Mount Sinai (US)
Foundation for the National Institutes of Health, Wellcome, National Institutes of Health, National Institute of Mental Health
Partnerships for the goals
Openalex Percentile: Top 4%
Neural dynamics and brain function
5.72
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