Distinct lithium-induced gene expression effects in lymphoblastoid cell lines from patients with bipolar disorder

Gabriel R. Fries, Gabriela D. Colpo, Nancy Monroy-Jaramillo, Junfei Zhao, Zhongming Zhao, Jodi G. Arnold, Charles L. Bowden, Consuelo Walss-Bass

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Lithium is the most commonly prescribed medication for the treatment of bipolar disorder (BD), yet the mechanisms underlying its beneficial effects are still unclear. We aimed to compare the effects of lithium treatment in lymphoblastoid cell lines (LCLs) from BD patients and controls. LCLs were generated from sixty-two BD patients (based on DSM-IV) and seventeen healthy controls matched for age, sex, and ethnicity. Patients were recruited from outpatient clinics from February 2012 to October 2014. LCLs were treated with 1 mM lithium for 7 days followed by microarray gene expression assay and validation by real-time quantitative PCR. Baseline differences between groups, as well as differences between vehicle- and lithium-treated cells within each group were analyzed. The biological significance of differentially expressed genes was examined by pathway enrichment analysis. No significant differences in baseline gene expression (adjusted p-value < 0.05) were detected between groups. Lithium treatment of LCLs from controls did not lead to any significant differences. However, lithium altered the expression of 236 genes in LCLs from patients; those genes were enriched for signaling pathways related to apoptosis. Among those genes, the alterations in the expression of PIK3CG, SERP1 and UPP1 were validated by real-time PCR. A significant correlation was also found between circadian functioning and CEBPG and FGF2 expression levels. In summary, our results suggest that lithium treatment induces expression changes in genes associated with the apoptosis pathway in BD LCLs. The more pronounced effects of lithium in patients compared to controls suggest a disease-specific effect of this drug.

Original languageEnglish (US)
Pages (from-to)1110-1119
Number of pages10
JournalEuropean Neuropsychopharmacology
Volume27
Issue number11
DOIs
StatePublished - Nov 2017

Keywords

  • Apoptosis
  • Bipolar disorder
  • Gene expression
  • Lithium
  • Lymphoblastoid cell lines
  • Morningness

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)

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