TY - JOUR
T1 - Distinct lithium-induced gene expression effects in lymphoblastoid cell lines from patients with bipolar disorder
AU - Fries, Gabriel R.
AU - Colpo, Gabriela D.
AU - Monroy-Jaramillo, Nancy
AU - Zhao, Junfei
AU - Zhao, Zhongming
AU - Arnold, Jodi G.
AU - Bowden, Charles L.
AU - Walss-Bass, Consuelo
N1 - Funding Information:
Funding for this study was provided by NIMH Advanced Center for Interventions and Services Research : Optimizing Outcomes in Bipolar Illness Interventions in Hispanic Communities 1P30MH086045 (CLB) and NIMH Calcium Study of Lymphoblasts in Bipolar Patients to Aid Diagnosis and Treatment 1R21MH097092-01 (CLB); the NIMH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
Publisher Copyright:
© 2017 Elsevier B.V. and ECNP
PY - 2017/11
Y1 - 2017/11
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Bipolar disorder
KW - Gene expression
KW - Lithium
KW - Lymphoblastoid cell lines
KW - Morningness
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U2 - 10.1016/j.euroneuro.2017.09.003
DO - 10.1016/j.euroneuro.2017.09.003
M3 - Article
C2 - 28939162
AN - SCOPUS:85029552170
VL - 27
SP - 1110
EP - 1119
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
SN - 0924-977X
IS - 11
ER -