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

INTRODUCTION: 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. OBJECTIVES: 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. METHODS: Patient-derived lymphoblastoid cell lines from the STAR*D study were used to rapidly generate cortical neurons and screen them for bupropion effects, for which the donor patients showed remission or non-remission. RESULTS: We provide evidence for biomarkers specific for bupropion response, including synaptic connectivity and morphology changes as well as specific gene expression alterations. CONCLUSIONS: 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. DISCLOSURE: This work was funded by Genetika+ Ltd, Jerusalem, Israel. YA, DK, EN, DL and TCS are employees of Genetika+ Ltd and received salary and/or stock options for the submitted work.