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Quantitative electroencephalography parameters as neurophysiological biomarkers of schizophrenia-related deficits: A Phase II substudy of patients treated with iclepertin (BI 425809)
Patients with schizophrenia experience cognitive impairment related to neural network dysfunction and deficits in sensory processing. These deficits are thought to be caused by N-methyl-D-aspartate receptor hypofunction and can be assessed in patient populations using electroencephalography (EEG). T...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9372178/ https://www.ncbi.nlm.nih.gov/pubmed/35953474 http://dx.doi.org/10.1038/s41398-022-02096-5 |
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author | Schultheis, Christian Rosenbrock, Holger Mack, Salome Rebecca Vinisko, Richard Schuelert, Niklas Plano, Andrea Süssmuth, Sigurd D. |
author_facet | Schultheis, Christian Rosenbrock, Holger Mack, Salome Rebecca Vinisko, Richard Schuelert, Niklas Plano, Andrea Süssmuth, Sigurd D. |
author_sort | Schultheis, Christian |
collection | PubMed |
description | Patients with schizophrenia experience cognitive impairment related to neural network dysfunction and deficits in sensory processing. These deficits are thought to be caused by N-methyl-D-aspartate receptor hypofunction and can be assessed in patient populations using electroencephalography (EEG). This substudy from a Phase II, randomized, double-blind, placebo-controlled, parallel-group study investigating the safety and efficacy of the novel glycine transporter-1 inhibitor, iclepertin (BI 425809), assessed the potential of EEG parameters as clinically relevant biomarkers of schizophrenia and response to iclepertin treatment. Eligible patients were randomized to once-daily add-on iclepertin (2, 5, 10, or 25 mg), or placebo (1:1:1:1:2 ratio) for 12 weeks. EEG data were recorded from a subgroup of patients (n = 79) at baseline and end of treatment (EoT). EEG parameters of interest were mismatch negativity (MMN), auditory steady-state response (ASSR), and resting state gamma power, and their correlations with clinical assessments. At baseline, MMN and ASSR exhibited consistent correlations with clinical assessments, indicating their potential value as neurophysiological biomarkers of schizophrenia-related deficits. ASSR measures were positively correlated to the MATRICS Consensus Cognitive Battery overall and neurocognitive composite scores; MMN amplitude was positively correlated with Positive and Negative Syndrome Scale scores. However, correlations between change from baseline (CfB) at EoT in clinical assessments, and baseline or CfB at EoT for EEG parameters were modest and inconsistent between dose groups, which might indicate low potential of these EEG parameters as predictive and treatment response biomarkers. Further methodological refinement is needed to establish EEG parameters as useful drug development tools for schizophrenia. |
format | Online Article Text |
id | pubmed-9372178 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-93721782022-08-13 Quantitative electroencephalography parameters as neurophysiological biomarkers of schizophrenia-related deficits: A Phase II substudy of patients treated with iclepertin (BI 425809) Schultheis, Christian Rosenbrock, Holger Mack, Salome Rebecca Vinisko, Richard Schuelert, Niklas Plano, Andrea Süssmuth, Sigurd D. Transl Psychiatry Article Patients with schizophrenia experience cognitive impairment related to neural network dysfunction and deficits in sensory processing. These deficits are thought to be caused by N-methyl-D-aspartate receptor hypofunction and can be assessed in patient populations using electroencephalography (EEG). This substudy from a Phase II, randomized, double-blind, placebo-controlled, parallel-group study investigating the safety and efficacy of the novel glycine transporter-1 inhibitor, iclepertin (BI 425809), assessed the potential of EEG parameters as clinically relevant biomarkers of schizophrenia and response to iclepertin treatment. Eligible patients were randomized to once-daily add-on iclepertin (2, 5, 10, or 25 mg), or placebo (1:1:1:1:2 ratio) for 12 weeks. EEG data were recorded from a subgroup of patients (n = 79) at baseline and end of treatment (EoT). EEG parameters of interest were mismatch negativity (MMN), auditory steady-state response (ASSR), and resting state gamma power, and their correlations with clinical assessments. At baseline, MMN and ASSR exhibited consistent correlations with clinical assessments, indicating their potential value as neurophysiological biomarkers of schizophrenia-related deficits. ASSR measures were positively correlated to the MATRICS Consensus Cognitive Battery overall and neurocognitive composite scores; MMN amplitude was positively correlated with Positive and Negative Syndrome Scale scores. However, correlations between change from baseline (CfB) at EoT in clinical assessments, and baseline or CfB at EoT for EEG parameters were modest and inconsistent between dose groups, which might indicate low potential of these EEG parameters as predictive and treatment response biomarkers. Further methodological refinement is needed to establish EEG parameters as useful drug development tools for schizophrenia. Nature Publishing Group UK 2022-08-11 /pmc/articles/PMC9372178/ /pubmed/35953474 http://dx.doi.org/10.1038/s41398-022-02096-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Schultheis, Christian Rosenbrock, Holger Mack, Salome Rebecca Vinisko, Richard Schuelert, Niklas Plano, Andrea Süssmuth, Sigurd D. Quantitative electroencephalography parameters as neurophysiological biomarkers of schizophrenia-related deficits: A Phase II substudy of patients treated with iclepertin (BI 425809) |
title | Quantitative electroencephalography parameters as neurophysiological biomarkers of schizophrenia-related deficits: A Phase II substudy of patients treated with iclepertin (BI 425809) |
title_full | Quantitative electroencephalography parameters as neurophysiological biomarkers of schizophrenia-related deficits: A Phase II substudy of patients treated with iclepertin (BI 425809) |
title_fullStr | Quantitative electroencephalography parameters as neurophysiological biomarkers of schizophrenia-related deficits: A Phase II substudy of patients treated with iclepertin (BI 425809) |
title_full_unstemmed | Quantitative electroencephalography parameters as neurophysiological biomarkers of schizophrenia-related deficits: A Phase II substudy of patients treated with iclepertin (BI 425809) |
title_short | Quantitative electroencephalography parameters as neurophysiological biomarkers of schizophrenia-related deficits: A Phase II substudy of patients treated with iclepertin (BI 425809) |
title_sort | quantitative electroencephalography parameters as neurophysiological biomarkers of schizophrenia-related deficits: a phase ii substudy of patients treated with iclepertin (bi 425809) |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9372178/ https://www.ncbi.nlm.nih.gov/pubmed/35953474 http://dx.doi.org/10.1038/s41398-022-02096-5 |
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