ArticleGenes, brain, and behavior2011
Functional genetic variation in the Rev-Erbα pathway and lithium response in the treatment of bipolar disorder.
Article in Genes, brain, and behavior, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 94 citations in OpenAlex.
- Genetic predictors of lithium response in an ethiopian cohort of patients with bipolar disorder.Annals of general psychiatry · 2026Article
- Lithium Therapeutic Functions: An Update on Pharmacokinetics, Pathophysiological Mechanisms of Action, Toxicity, and Side Effects.Molecular neurobiology · 2026Review
- Circadian clock genes and cell survival in bipolar disorder: Insights into lithium responsiveness and molecular mechanisms in patient-derived neural progenitor cells and mouse neurons.The FEBS journal · 2025Article
- Bipolar Disorder, Circadian Rhythm and Clock Genes.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2024Review
- Differential contributions of circadian clock genes to cell survival in bipolar disorder patient derived neuronal progenitor cells distinguishes lithium responders and non-responders.Research square · 2024Article
- Pharmacogenomics and response to lithium in bipolar disorder.Pharmacogenomics · 2024Review
- Contributions of circadian clock genes to cell survival in fibroblast models of lithium-responsive bipolar disorder.European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2023Article
- Nuclear receptor Nr1d1 alleviates asthma by abating GATA3 gene expression and Th2 cell differentiation.Cellular and molecular life sciences : CMLS · 2022Article
- Neurobiological and behavioral mechanisms of circadian rhythm disruption in bipolar disorder: A critical multi-disciplinary literature review and agenda for future research from the ISBD task force on chronobiology.Bipolar disorders · 2022Review
- Genetic and Epigenetic Markers of Lithium Response.International journal of molecular sciences · 2022Review
- Pharmacogenomics of Lithium Response in Bipolar Disorder.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Every Night and Every Morn: Effect of Variation inFrontiers in psychiatry · 2021Article
- The Genetics of Response to and Side Effects of Lithium Treatment in Bipolar Disorder: Future Research Perspectives.Frontiers in pharmacology · 2021Review
- Lithium response in bipolar disorder correlates with improved cell viability of patient derived cell lines.Scientific reports · 2020Article
- Pharmacogenomic Characterization in Bipolar Spectrum Disorders.Pharmaceutics · 2019Review
- High expression of NR1D1 is associated with good prognosis in triple-negative breast cancer patients treated with chemotherapy.Breast cancer research : BCR · 2019Article
- Pharmacological Manipulation of the Circadian Clock: A Possible Approach to the Management of Bipolar Disorder.CNS drugs · 2019Review
- Role of Per3, a circadian clock gene, in embryonic development of mouse cerebral cortex.Scientific reports · 2019Article
- Sleep Disturbance in Bipolar Disorder: Neuroglia and Circadian Rhythms.Frontiers in psychiatry · 2019Review
- The Role of Pharmacogenomics in Bipolar Disorder: Moving Towards Precision Medicine.Molecular diagnosis & therapy · 2018Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Bipolar disorder (BD) is characterized by disruptions in circadian rhythms such as sleep and daily activity that often normalize after lithium treatment in responsive patients. As lithium is known to interact with the circadian clock, we hypothesized that variation in circadian 'clock genes' would be associated with lithium response in BD. We determined genotype for 16 variants in seven circadian clock genes and conducted a candidate gene association study of these in 282 Caucasian patients with BD who were previously treated with lithium. We found that a variant in the promoter of NR1D1 encoding Rev-Erbα (rs2071427) and a second variant in CRY1 (rs8192440) were nominally associated with good treatment response. Previous studies have shown that lithium regulates Rev-Erbα protein stability by inhibiting glycogen synthase kinase 3β (GSK3β). We found that GSK3β genotype was also suggestive of a lithium response association, but not statistically significant. However, when GSK3β and NR1D1 genotypes were considered together, they predicted lithium response robustly and additively in proportion to the number of response-associated alleles. Using lymphoblastoid cell lines from patients with BD, we found that both the NR1D1 and GSK3β variants are associated with functional differences in gene expression. Our findings support a role for Rev-Erbα in the therapeutic mechanism of lithium and suggest that the interaction between Rev-Erbα and GSK3β may warrant further study.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.