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

Published online by Cambridge University Press:  13 August 2021

Y. Avior*
Affiliation:
R&d, Genetika+, Jerusalem, Israel
S. Ron
Affiliation:
R&d, Genetika+, Jerusalem, Israel
D. Kroitorou
Affiliation:
R&d, Genetika+, Jerusalem, Israel
E. Nitzan
Affiliation:
R&d, Genetika+, Jerusalem, Israel
B. Corneo
Affiliation:
Stem Cell Core Facility, Columbia University, New York City, United States of America
D. Laifenfeld
Affiliation:
R&d, Genetika+, Jerusalem, Israel
T. Cohen Solal
Affiliation:
R&d, Genetika+, Jerusalem, Israel
*
*Corresponding author.

Abstract

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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.

Type
Abstract
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of the European Psychiatric Association
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