Network-based integrative analysis of lithium response in bipolar disorder using transcriptomic and GWAS data
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ABSTRACT:
PROVIDER: PRJNA844997 | ENA |
REPOSITORIES: ENA
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Project description:Lithium is the gold standard treatment for bipolar disorder. The goal of this study was to identify gene expression networks associated with lithium response. RNAseq data was obtained from IPSC derived neurons from lithium responders and non-responders. Focal adhesion was the network most associated with response.
2022-06-09 | GSE205422 | GEO
Project description:Bipolar disorder is a severe and heritable psychiatric disorder and affects up to 1% of the population worldwide. Lithium is recommended as first-line treatment for the maintenance treatment of bipolar-affective disorder in current guidelines, its molecular modes of action are however poorly understood. Cell models derived from bipolar patients could prove useful to gain more insight in the molecular mechanisms of bipolar disorder and the common pharmacological treatments. As primary neuronal cell lines cannot be easily derived from patients, peripheral cell models should be evaluated in their usefulness to study pathomechanisms and the mode of action of medication as well as in regard to develop biomarkers for diagnosis and treatment response.
2018-12-01 | GSE66196 | GEO
Project description:BACKGROUND: Bipolar disorder (BD) is a highly heritable mood disorder with complex genetic architecture and poorly understood etiology. Previous transcriptomic BD studies have had inconsistent findings due to issues such as small sample sizes and difficulty in adequately accounting for confounders like medication use. METHODS: We performed a differential expression analysis in a well-characterized BD case-control sample (Nsubjects = 480) by RNA sequencing of whole blood. We further performed co-expression network analysis, functional enrichment, and cell type decomposition, and integrated differentially expressed genes with genetic risk. RESULTS: While we observed widespread differential gene expression patterns between affected and unaffected individuals, these effects were largely linked to lithium treatment at the time of blood draw (FDR < 0.05, Ngenes = 976) rather than BD diagnosis itself (FDR < 0.05, Ngenes = 6). These lithium-associated genes were enriched for cell signaling and immune response functional annotations, among others, and were associated with neutrophil cell-type proportions, which were elevated in lithium users. Neither genes with altered expression in cases nor in lithium users were enriched for BD, schizophrenia, and depression genetic risk based on information from genome-wide association studies, nor was gene expression associated with polygenic risk scores for BD. CONCLUSIONS: These findings suggest that BD is associated with minimal changes in whole blood gene expression independent of medication use but emphasize the importance of accounting for medication use and cell type heterogeneity in psychiatric transcriptomic studies. The results of this study add to mounting evidence of lithium's cell signaling and immune-related mechanisms.
2019-10-24 | GSE124326 | GEO
Project description:Whole blood transcriptome analysis in bipolar disorder reveals strong lithium effect
| PRJNA511612 | ENA
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:Lithium treatment is commonly used to treat bipolar disorder. However, this treatment disrupts kidney fuctionality. We used microdissected cortical collecting ducts to study proteomics and ultimately discover what changes occur in protein expression after 72-hr lithium treatment.
2019-07-01 | PXD010118 | Pride
Project description:Human neuronal-like cells (NT2-N) were treated with either lamotrigine (50 µM), lithium (2.5 mM), quetiapine (50 µM), valproate (0.5 mM) or vehicle control for 24 hours. Genome wide mRNA expression was quantified by RNA-sequencing. Results offer insights on the mechanism(s) of action of bipolar disorder drugs at the transcriptional level.
2022-04-08 | GSE197966 | GEO
Project description:Lithium is a first-line treatment for bipolar disorder, where it acts as a mood-stabilizing agent. Although its precise mechanism remains unclear, neuroimaging studies have shown that lithium accumulates in the hippocampus and that chronic use amongst bipolar disorder patients is associated with larger hippocampal volumes. Here, we tested the chronic effects of low (0.75 mM) and high (2.25 mM) doses of lithium on human hippocampal progenitor cells and used immunocytochemistry to investigate the effects of lithium on cell parameters implicated in neurogenesis. Corresponding RNA-sequencing and gene-set enrichment analyses were used to evaluate whether genes affected by lithium in our model overlap with those regulating the volume of specific layers of the dentate gyrus. We observed that high-dose lithium treatment in human hippocampal progenitors increased the generation of neuroblasts (P ≤ 0.01), neurons (P ≤ 0.01), and glia (P ≤ 0.001), alongside the expression of genes which regulate the volume of the molecular layer of the dentate gyrus. This study provides empirical support that adult hippocampal neurogenesis and gliogenesis are mechanisms that could contribute to the effects of lithium on human hippocampal volume.
2021-09-30 | GSE184930 | GEO
Project description:Analysis of gene-expression changes in treatment responders vs non-responders to two different treatments among subjectrs participating in LiTMUS. Results provide information on pathways that may be involved in the clinical response to Lithium in patients with bipolar disorder. Total RNA isolated from PAXgene blood RNA tubes from 60 subjects with bipolar disorder, randomized to 2 treatment groups (OPT, Li+OPT) at 2 time-points (baseline, 1 month after treatment)
2013-03-26 | E-GEOD-45484 | biostudies-arrayexpress