Mismatch negativity as EEG biomarker supporting CNS drug development: a transnosographic and translational study

Author:

Loiodice SimonORCID,Drinkenburg Wilhelmus H.,Ahnaou AbdallahORCID,McCarthy Andrew,Viardot Geoffrey,Cayre Emilie,Rion Bertrand,Bertaina-Anglade Valérie,Mano Marsel,L’Hostis Philippe,Drieu La Rochelle Christophe,Kas Martien J.ORCID,Danjou Philippe

Abstract

AbstractThe lack of translation from basic research into new medicines is a major challenge in CNS drug development. The need to use novel approaches relying on (i) patient clustering based on neurobiology irrespective to symptomatology and (ii) quantitative biomarkers focusing on evolutionarily preserved neurobiological systems allowing back-translation from clinical to nonclinical research has been highlighted. Here we sought to evaluate the mismatch negativity (MMN) response in schizophrenic (SZ) patients, Alzheimer’s disease (AD) patients, and age-matched healthy controls. To evaluate back-translation of the MMN response, we developed EEG-based procedures allowing the measurement of MMN-like responses in a rat model of schizophrenia and a mouse model of AD. Our results indicate a significant MMN attenuation in SZ but not in AD patients. Consistently with the clinical findings, we observed a significant attenuation of deviance detection (~104.7%) in rats subchronically exposed to phencyclidine, while no change was observed in APP/PS1 transgenic mice when compared to wild type. This study provides new insight into the cross-disease evaluation of the MMN response. Our findings suggest further investigations to support the identification of neurobehavioral subtypes that may help patients clustering for precision medicine intervention. Furthermore, we provide evidence that MMN could be used as a quantitative/objective efficacy biomarker during both preclinical and clinical stages of SZ drug development.

Publisher

Springer Science and Business Media LLC

Subject

Biological Psychiatry,Cellular and Molecular Neuroscience,Psychiatry and Mental health

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