Depression patient-derived cortical neurons reveal potential biomarkers for antidepressant response

抑郁症患者来源的皮质神经元揭示了抗抑郁反应的潜在生物标志物

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作者:Yishai Avior, Shiri Ron, Dana Kroitorou, Claudia Albeldas, Vitaly Lerner, Barbara Corneo, Erez Nitzan, Daphna Laifenfeld, Talia Cohen Solal

Abstract

Major depressive disorder is highly prevalent worldwide and has been affecting an increasing number of people each year. Current first line antidepressants show merely 37% remission, and physicians are forced to use a trial-and-error approach when choosing a single antidepressant out of dozens of available medications. We sought to identify a method of testing that would provide patient-specific information on whether a patient will respond to a medication using in vitro modeling. Patient-derived lymphoblastoid cell lines from the Sequenced Treatment Alternatives to Relieve Depression study were used to rapidly generate cortical neurons and screen them for bupropion effects, for which the donor patients showed remission or non-remission. We provide evidence for biomarkers specific for bupropion response, including synaptic connectivity and morphology changes as well as specific gene expression alterations. These biomarkers support the concept of personalized antidepressant treatment based on in vitro platforms and could be utilized as predictors to patient response in the clinic.

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