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Electrophysiological measures from human iPSC-derived neurons are associated with schizophrenia clinical status and predict individual cognitive performance.

ABSTRACT: Neurons derived from human induced pluripotent stem cells (hiPSCs) have been used to model basic cellular aspects of neuropsychiatric disorders, but the relationship between the emergent phenotypes and the clinical characteristics of donor individuals has been unclear. We analyzed RNA expression and indices of cellular function in hiPSC-derived neural progenitors and cortical neurons generated from 13 individuals with high polygenic risk scores (PRSs) for schizophrenia (SCZ) and a clinical diagnosis of SCZ, along with 15 neurotypical individuals with low PRS. We identified electrophysiological measures in the patient-derived neurons that implicated altered Na+ channel function, action potential interspike interval, and gamma-aminobutyric acid-ergic neurotransmission. Importantly, electrophysiological measures predicted cardinal clinical and cognitive features found in these SCZ patients. The identification of basic neuronal physiological properties related to core clinical characteristics of illness is a potentially critical step in generating leads for novel therapeutics.

SUBMITTER: Page SC

PROVIDER: S-EPMC8784142 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Electrophysiological measures from human iPSC-derived neurons are associated with schizophrenia clinical status and predict individual cognitive performance.

Page Stephanie Cerceo SC Sripathy Srinidhi Rao SR Farinelli Federica F Ye Zengyou Z Wang Yanhong Y Hiler Daniel J DJ Pattie Elizabeth A EA Nguyen Claudia V CV Tippani Madhavi M Moses Rebecca L RL Chen Huei-Ying HY Tran Matthew Nguyen MN Eagles Nicholas J NJ Stolz Joshua M JM Catallini Joseph L JL Soudry Olivia R OR Dickinson Dwight D Berman Karen F KF Apud Jose A JA Weinberger Daniel R DR Martinowich Keri K Jaffe Andrew E AE Straub Richard E RE Maher Brady J BJ

Proceedings of the National Academy of Sciences of the United States of America 20220101 3

Neurons derived from human induced pluripotent stem cells (hiPSCs) have been used to model basic cellular aspects of neuropsychiatric disorders, but the relationship between the emergent phenotypes and the clinical characteristics of donor individuals has been unclear. We analyzed RNA expression and indices of cellular function in hiPSC-derived neural progenitors and cortical neurons generated from 13 individuals with high polygenic risk scores (PRSs) for schizophrenia (SCZ) and a clinical diagn ...[more]

PMID: 35017298

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Electrophysiological measures from human iPSC-derived neurons are associated with schizophrenia clinical status and predict individual cognitive performance.

Publications

Electrophysiological measures from human iPSC-derived neurons are associated with schizophrenia clinical status and predict individual cognitive performance.

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