ArticleMolecular psychiatry2018
Neurons derived from patients with bipolar disorder divide into intrinsically different sub-populations of neurons, predicting the patients' responsiveness to lithium.
Article in Molecular psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 2 of them syntheses that pooled it.
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Who cites it
97 citing papers in PubMed, 2 syntheses or guidelines pooled it, 181 citations in OpenAlex.
- In vivo hippocampal subfield volumes in bipolar disorder-A mega-analysis from The Enhancing Neuro Imaging Genetics through Meta-Analysis Bipolar Disorder Working Group.Human brain mapping · 2022Pooled it
- Mental health dished up-the use of iPSC models in neuropsychiatric research.Journal of neural transmission (Vienna, Austria : 1996) · 2020Pooled it
- The Toll-Like Receptor Signalling Pathway Is Altered in iPSC-Derived Cortical Networks From People With Bipolar Disorder.Bipolar disorders · 2026Article
- Mll5 haploinsufficiency attenuates microglial phagocytosis through dysregulated TREM2-SGK3-GSK3β signaling and recapitulates ASD-like behaviors in mice.Nature communications · 2026Article
- Extracellular vesicles from stem cells rescue cellular phenotypes and behavioral deficits in SHANK3-associated ASD neuronal and mouse models.Cell death & disease · 2026Article
- Astrocyte Ezrin defines resilience to stress-induced depressive behaviours in mice.National science review · 2026Article
- At 75 Years, Is Lithium the Gold Standard in Bipolar Disorder?Pharmaceuticals (Basel, Switzerland) · 2025Review
- Differential effects of lithium on metabolic dysfunctions in astrocytes derived from bipolar disorder patients.Molecular psychiatry · 2025Article
- Overlap and Divergence in Ketamine and Lithium Response in Bipolar Disorder: A Scoping Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Lithium partially rescues gene expression and enhancer activity from heterozygous knockout of AKAP11 while inducing novel differential changes.Scientific reports · 2025Article
- The effects of bipolar disorder granule cell hyperexcitability and lithium therapy on pattern separation in a computational model of the dentate gyrus.Translational psychiatry · 2025Article
- A pancreas-hippocampus feedback mechanism regulates circadian changes in depression-related behaviors.Nature neuroscience · 2025Article
- Transcriptomic and epigenomic consequences of heterozygous loss-of-function mutations in AKAP11, a shared risk gene for bipolar disorder and schizophrenia.Molecular psychiatry · 2025Article
- Detecting suicide risk in bipolar disorder patients from lymphoblastoid cell lines genetic signatures.Translational psychiatry · 2025Article
- iPSC-derived cerebral organoids reveal mitochondrial, inflammatory and neuronal vulnerabilities in bipolar disorder.Translational psychiatry · 2025Article
- Synaptotagmin-7 deficit causes insulin hypoactivity and contributes to behavioral alterations in mice.iScience · 2025Article
- Entanglement and coherence in pure and doped Posner molecules.Scientific reports · 2025Article
- The Mechanisms of Lithium Action: The Old and New Findings.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Linking Mitochondrial Dysfunction, Neurotransmitter, and Neural Network Abnormalities and Mania: Elucidating Neurobiological Mechanisms of the Therapeutic Effect of the Ketogenic Diet in Bipolar Disorder.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2025Review
- The Impact of Electrophysiological Diversity on Pattern Completion in Lithium Nonresponsive Bipolar Disorder: A Computational Modeling Approach.Brain and behavior · 2025Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 8 institutions in 4 countries.
Funding
Abstract
Bipolar disorder (BD) is a progressive psychiatric disorder with more than 3% prevalence worldwide. Affected individuals experience recurrent episodes of depression and mania, disrupting normal life and increasing the risk of suicide greatly. The complexity and genetic heterogeneity of psychiatric disorders have challenged the development of animal and cellular models. We recently reported that hippocampal dentate gyrus (DG) neurons differentiated from induced pluripotent stem cell (iPSC)-derived fibroblasts of BD patients are electrophysiologically hyperexcitable. Here we used iPSCs derived from Epstein-Barr virus-immortalized B-lymphocytes to verify that the hyperexcitability of DG-like neurons is reproduced in this different cohort of patients and cells. Lymphocytes are readily available for research with a large number of banked lines with associated patient clinical description. We used whole-cell patch-clamp recordings of over 460 neurons to characterize neurons derived from control individuals and BD patients. Extensive functional analysis showed that intrinsic cell parameters are very different between the two groups of BD neurons, those derived from lithium (Li)-responsive (LR) patients and those derived from Li-non-responsive (NR) patients, which led us to partition our BD neurons into two sub-populations of cells and suggested two different subdisorders. Training a Naïve Bayes classifier with the electrophysiological features of patients whose responses to Li are known allows for accurate classification with more than 92% success rate for a new patient whose response to Li is unknown. Despite their very different functional profiles, both populations of neurons share a large, fast after-hyperpolarization (AHP). We therefore suggest that the large, fast AHP is a key feature of BD and a main contributor to the fast, sustained spiking abilities of BD neurons. Confirming our previous report with fibroblast-derived DG neurons, chronic Li treatment reduced the hyperexcitability in the lymphoblast-derived LR group but not in the NR group, strengthening the validity and utility of this new human cellular model of BD.
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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.