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Eur Neuropsychopharmacol. 2017 Nov;27(11):1110-1119. doi: 10.1016/j.euroneuro.2017.09.003. Epub 2017 Sep 20.

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

Author information

1
Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, United States.
2
Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, United States; Department of Genetics, National Institute of Neurology and Neurosurgery, Manuel Velasco Suárez, Insurgentes Sur 3877 Col. La Fama, Tlalpan, C.P. 14269 Mexico City, Mexico.
3
Bioinformatics and Systems Medicine Laboratory (BSML), Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, 7000 Fannin Street, Houston, TX 77030, United States.
4
Bioinformatics and Systems Medicine Laboratory (BSML), Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, 7000 Fannin Street, Houston, TX 77030, United States; Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, 1200 Pressler Street, Houston, TX 77030, United States.
5
Department of Psychiatry, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, United States.
6
Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, United States. Electronic address: Consuelo.walssbass@uth.tmc.edu.

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 1mM 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.

KEYWORDS:

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

PMID:
28939162
PMCID:
PMC5685885
DOI:
10.1016/j.euroneuro.2017.09.003
[Indexed for MEDLINE]
Free PMC Article

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