Immunoglobulin genes expressed in lymphoblastoid cell lines discern and predict lithium response in bipolar disorder patients

Liron Mizrahi, Ashwani Choudhary, Polina Ofer, Gabriela Goldberg, Elena Milanesi, John R. Kelsoe, David Gurwitz, Martin Alda, Fred H. Gage, Shani Stern

Research output: Contribution to journalArticlepeer-review

Abstract

Bipolar disorder (BD) is a neuropsychiatric mood disorder manifested by recurrent episodes of mania and depression. More than half of BD patients are non-responsive to lithium, the first-line treatment drug, complicating BD clinical management. Given its unknown etiology, it is pertinent to understand the genetic signatures that lead to variability in lithium response. We discovered a set of differentially expressed genes (DEGs) from the lymphoblastoid cell lines (LCLs) of 10 controls and 19 BD patients belonging mainly to the immunoglobulin gene family that can be used as potential biomarkers to diagnose and treat BD. Importantly, we trained machine learning algorithms on our datasets that predicted the lithium response of BD subtypes with minimal errors, even when used on a different cohort of 24 BD patients acquired by a different laboratory. This proves the scalability of our methodology for predicting lithium response in BD and for a prompt and suitable decision on therapeutic interventions.

Original languageEnglish
Pages (from-to)4280-4293
Number of pages14
JournalMolecular Psychiatry
Volume28
Issue number10
DOIs
StatePublished - Oct 2023

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Molecular Biology

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