ArticleNeuropharmacology2016
Calcium channel genes associated with bipolar disorder modulate lithium's amplification of circadian rhythms.
Article in Neuropharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.
What it found
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Who cites it
28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 66 citations in OpenAlex.
- The genetic overlap between mood disorders and cardiometabolic diseases: a systematic review of genome wide and candidate gene studies.Translational psychiatry · 2017Pooled it
- A systematic review of calcium channel antagonists in bipolar disorder and some considerations for their future development.Molecular psychiatry · 2016Pooled it
- Article
- Genetic Polymorphisms Associated with Lithium Response in Bipolar Disorder: An Integrative Review and In Silico Protein-Protein Interaction Analysis.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Article
- Pathophysiological Insights and Multimodal Interventions in Chronic Tinnitus, Anxiety, and Sleep Disorders.Nature and science of sleep · 2025Review
- Differential serum levels of CACNA1C, circadian rhythm and stress response molecules in subjects with bipolar disorder: Associations with genetic and clinical factors.Journal of affective disorders · 2024Article
- Differential Serum Levels of CACNA1C, Circadian Rhythm and Stress Response Molecules in Subjects with Bipolar Disorder: Associations with Genetic and Clinical Factors.medRxiv : the preprint server for health sciences · 2024Article
- Effects of lithium isotopes on sodium/lithium co-transport and calcium efflux through the sodium/calcium/lithium exchanger in mitochondria.Frontiers in physiology · 2024Article
- 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
- Serum from Myalgic encephalomyelitis/chronic fatigue syndrome patients causes loss of coherence in cellular circadian rhythms.Journal of neuroimmunology · 2023Article
- Regulation of dendritic spines in the amygdala following sleep deprivation.Frontiers in sleep · 2023Article
- The impact of lithium on circadian rhythms and implications for bipolar disorder pharmacotherapy.Neuroscience letters · 2022Review
- 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
- Investigation of genetic loci shared between bipolar disorder and risk-taking propensity: potential implications for pharmacological interventions.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Circadian rhythms in bipolar disorder patient-derived neurons predict lithium response: preliminary studies.Molecular psychiatry · 2021Article
- Sleep and Memory Consolidation Dysfunction in Psychiatric Disorders: Evidence for the Involvement of Extracellular Matrix Molecules.Frontiers in neuroscience · 2021Review
- Targeting Mitochondrial Dysfunction for Bipolar Disorder.Current topics in behavioral neurosciences · 2021Review
- Reciprocal Relationship Between Calcium Signaling and Circadian Clocks: Implications for Calcium Homeostasis, Clock Function, and Therapeutics.Frontiers in molecular neuroscience · 2021Review
- Pharmacological Manipulation of the Circadian Clock: A Possible Approach to the Management of Bipolar Disorder.CNS drugs · 2019Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledBipolar disorder (BD) is associated with mood episodes and low amplitude circadian rhythms. Previously, we demonstrated that fibroblasts grown from BD patients show weaker amplification of circadian rhythms by lithium compared to control cells. Since calcium signals impact upon the circadian clock, and L-type calcium channels (LTCC) have emerged as genetic risk factors for BD, we examined whether loss of function in LTCCs accounts for the attenuated response to lithium in BD cells. We used fluorescent dyes to measure Ca(2+) changes in BD and control fibroblasts after lithium treatment, and bioluminescent reporters to measure Per2::luc rhythms in fibroblasts from BD patients, human controls, and mice while pharmacologically or genetically manipulating calcium channels. Longitudinal expression of LTCC genes (CACNA1C, CACNA1D and CACNB3) was then measured over 12-24 h in BD and control cells. Our results indicate that independently of LTCCs, lithium stimulated intracellular Ca(2+) less effectively in BD vs. control fibroblasts. In longitudinal studies, pharmacological inhibition of LTCCs or knockdown of CACNA1A, CACNA1C, CACNA1D and CACNB3 altered circadian rhythm amplitude. Diltiazem and knockdown of CACNA1C or CACNA1D eliminated lithium's ability to amplify rhythms. Knockdown of CACNA1A or CACNB3 altered baseline rhythms, but did not affect rhythm amplification by lithium. In human fibroblasts, CACNA1C genotype predicted the amplitude response to lithium, and the expression profiles of CACNA1C, CACNA1D and CACNB3 were altered in BD vs. CONTROLS: We conclude that in cells from BD patients, calcium signaling is abnormal, and that LTCCs underlie the failure of lithium to amplify circadian rhythms.
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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.