Gene and MicroRNA expression data from lymphoblastoid cell lines from patients with bipolar disorder
Ontology highlight
ABSTRACT:
ORGANISM(S): synthetic construct Homo sapiens
PROVIDER: GSE93114 | GEO | 2017/07/04
SECONDARY ACCESSION(S): PRJNA360075
REPOSITORIES: GEO
Similar Datasets
Project description:Bipolar disorder (BD) (1% of the general population) is a major affective disorder characterized by recurrent manic and depressive episodes and associated with considerable burden and costs. Lithium (Li) is the first line treatment for relapse prevention in bipolar disorders with many patients who remain asymptomatic for several years (even decades). In addition, it is the only psychoactive drug that has demonstrated efficacy in suicide prevention. However a large proportion of patients is experiencing very high relapse rates (overall between 70 and 80% relapse, 2 years after a major episode). Li mechanism of action is rather complex and still not fully understood despite extensive studies. In order to explore potential lithium effects on global gene and miRNAs expression, we initiated a study in cell-lines from excellent responders (ER) and non-responders (NR) bipolar patients Briefly, long-term treatment response to lithium was evaluated using a validated scale “Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder” , also known as the Alda scale. In our sample we analyzed dichotomous phenotypes for lithium response: patients with total score (TS) higher or equal to 7, characterized as ER; and patients with TS lower than 2, characterized as NR according to the literature.
2017-07-04 | GSE93113 | GEO
Project description:Bipolar disorder (BD) (1% of the general population) is a major affective disorder characterized by recurrent manic and depressive episodes and associated with considerable burden and costs. Lithium (Li) is the first line treatment for relapse prevention in bipolar disorders with many patients who remain asymptomatic for several years (even decades). In addition, it is the only psychoactive drug that has demonstrated efficacy in suicide prevention. However a large proportion of patients is experiencing very high relapse rates (overall between 70 and 80% relapse, 2 years after a major episode). Li mechanism of action is rather complex and still not fully understood despite extensive studies. In order to explore potential lithium effects on global gene and miRNAs expression, we initiated a study in cell-lines from excellent responders (ER) and non-responders (NR) bipolar patients Briefly, long-term treatment response to lithium was evaluated using a validated scale “Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder” , also known as the Alda scale. In our sample we analyzed dichotomous phenotypes for lithium response: patients with total score (TS) higher or equal to 7, characterized as ER; and patients with TS lower than 2, characterized as NR according to the literature.
2017-07-04 | GSE93112 | GEO
Project description:Gene and MicroRNA expression data from lymphoblastoid cell lines from patients with bipolar disorder
| PRJNA360075 | ENA
Project description: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.
| S-EPMC5685885 | biostudies-literature
Project description:Bipolar disorder (BD) has been previously associated with accelerated aging, and recent investigations have started to explore the potential anti-aging effects of BD treatments. Lithium, the most commonly used mood stabilizer, has been suggested to impact telomere length in specific populations, although its effects on other aging biomarkers, such as epigenetic aging, have never been investigated. We assessed the in vitro effects of lithium on telomere length and epigenetic aging in lymphoblastoid cell lines (LCLs) from 14 patients with BD and 14 controls, all matched for age, sex, and ethnicity. Our results showed that telomere length significantly correlated with chronological age in LCLs in both groups and that BD patients have shorter telomere lengths compared to controls at baseline (vehicle treatment), confirming previous in vivo findings. Moreover, lithium treatment significantly increased telomere length in LCLs from patients, but not in controls. On the other hand, epigenetic age did not correlate with chronological age and was not shown to differ between patients and controls. In addition, lithium did not induce any changes in epigenetic age in cells from either patients or controls. Overall, our results support previous reports of an anti-aging effect of lithium based on its modulation of telomere length and suggest a different lithium effect in cells from patients and controls. Finally, we also discuss the limitations of using transformed LCLs for the study of DNA methylation mechanisms.
| S-EPMC7484018 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-04-08 | GSE137921 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-07-06 | GSE116638 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-05-03 | GSE112525 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-07-19 | GSE179922 | GEO
Project description:G-protein coupled receptor kinase-3 (GRK3), translated from the gene, ADRBK2 has been implicated as a candidate molecule for bipolar disorder through multiple, converging lines of evidence. In some individuals, the ADRBK2 gene harbors the A-haplotype, a collection of single nucleotide polymorphisms (SNPs) previously associated with an increased risk for bipolar disorder. Because the A-haplotype encompasses the ADRBK2 promoter, we hypothesized that it may alter the regulation of gene expression. Using histone H3 acetylation to infer promoter activity in lymphoblastoid cells from patients with bipolar disorder, we examined the A-haplotype within its genomic context and determined that at least four of its SNPs are present in transcriptionally active portions of the promoter. However, using chromatin immunoprecipitation followed by allele-specific PCR in samples heterozygous for the A-haplotype, we found no evidence of altered levels of acetylated histone H3 at the affected allele compared to the common allele. Similarly, using a transcribed SNP to discriminate expressed ADRBK2 mRNA strands by allele of origin; we found that the A-haplotype did not confer an allelic-expression imbalance. Our data suggest that while the A-haplotype is situated in active regulatory sequence, the risk-associated SNPs do not appear to affect ADRBK2 gene regulation at the level of histone H3 acetylation nor do they confer measurable changes in transcription in lymphoblastoid cells. However, tissue-specific mechanisms by which the A-haplotype could affect ADRBK2 in the central nervous system cannot be excluded.
| S-EPMC2830298 | biostudies-literature