Electrophysiological measures from human iPSC-derived neurons are associated with schizophrenia clinical status and predict individual cognitive performance
Stephanie C. Page, Srinidhi Rao Sripathy, Federica Farinelli, Zengyou Ye, Yanhong Wang, Daniel J. Hiler, Elizabeth A. Pattie, Claudia V. Nguyen, Madhavi Tippani, Rebecca L. Moses, Huei-Ying Chen, Matthew N. Tran, Nicholas J. Eagles, Joshua M. Stolz, Joseph Catallini, Olivia R. Soudry, Dwight Dickinson, Karen F. Berman, José Apud, Daniel R. Weinberger, Keri Martinowich, Andrew E. Jaffe, Richard E. Straub, Brady J. Maher
Abstract
Significance Schizophrenia (SCZ) is a complex, highly heritable, neurodevelopmental disorder with marked clinical heterogeneity and no clear pathological mechanism or cellular pathology. The polygenic nature of the disorder has hindered our ability to model the disorder in the laboratory. Prior studies of cortical neurons differentiated from SCZ patient and control hiPSCs have identified interesting differences but their relevance to clinical illness in adults remains unclear. We now identify electrophysiological measures that associate with diagnosis and/or predict the severity of clinical and cognitive features of individual adult donors. These results demonstrate neurophysiological measures that are related to the patient’s personal clinical characteristics, which may help with patient stratification and the development of novel biomarkers and therapeutic targets.