ArticleBiological psychiatry2020
A Physiological Instability Displayed in Hippocampal Neurons Derived From Lithium-Nonresponsive Bipolar Disorder Patients.
Article in Biological psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.
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Who cites it
23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 51 citations in OpenAlex.
- Uncovering convergence and divergence between autism and schizophrenia using genomic tools and patients' neurons.Molecular psychiatry · 2025Pooled it
- Pooled it
- Thyroid hormone augmentation for bipolar disorder: a neurobiological and clinical narrative review.International journal of bipolar disorders · 2026Review
- Novel epigenetic loci identified from an epigenome-wide association study underlying brain structural changes in bipolar disorder.Psychological medicine · 2026Article
- Extracellular vesicles from stem cells rescue cellular phenotypes and behavioral deficits in SHANK3-associated ASD neuronal and mouse models.Cell death & disease · 2026Article
- Overlap and Divergence in Ketamine and Lithium Response in Bipolar Disorder: A Scoping Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- 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
- Cellular and proteomic differences associated with lithium response in olfactory neuroepithelium cells of bipolar disorder patients.Molecular medicine (Cambridge, Mass.) · 2025Article
- Detecting suicide risk in bipolar disorder patients from lymphoblastoid cell lines genetic signatures.Translational psychiatry · 2025Article
- The Impact of Electrophysiological Diversity on Pattern Completion in Lithium Nonresponsive Bipolar Disorder: A Computational Modeling Approach.Brain and behavior · 2025Article
- Monozygotic twins discordant for schizophrenia differ in maturation and synaptic transmission.Molecular psychiatry · 2024Article
- Upregulated ECM genes and increased synaptic activity in Parkinson's human DA neurons with PINK1/ PRKN mutations.NPJ Parkinson's disease · 2024Article
- Exploring mood disorders and treatment options using human stem cells.Genetics and molecular biology · 2024Article
- Mechanisms of Sustained Increases inBrain sciences · 2023Article
- Immunoglobulin genes expressed in lymphoblastoid cell lines discern and predict lithium response in bipolar disorder patients.Molecular psychiatry · 2023Article
- Early maturation and hyperexcitability is a shared phenotype of cortical neurons derived from different ASD-associated mutations.Translational psychiatry · 2023Article
- Cellular Genome-wide Association Study Identifies Common Genetic Variation Influencing Lithium-Induced Neural Progenitor Proliferation.Biological psychiatry · 2023Article
- A critical evaluation of dynamical systems models of bipolar disorder.Translational psychiatry · 2022Review
- Reduced synaptic activity and dysregulated extracellular matrix pathways in midbrain neurons from Parkinson's disease patients.NPJ Parkinson's disease · 2022Article
- Induced Pluripotent Stem Cells in Psychiatry: An Overview and Critical Perspective.Biological psychiatry · 2021Review
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Authors and funding
14 authors at 4 institutions in 4 countries.
Funding
Abstract
backgroundWe recently reported a hyperexcitability phenotype displayed in dentate gyrus granule neurons derived from patients with bipolar disorder (BD) as well as a hyperexcitability that appeared only in CA3 pyramidal hippocampal neurons that were derived from patients with BD who responded to lithium treatment (lithium responders) and not in CA3 pyramidal hippocampal neurons that were derived from patients with BD who did not respond to lithium (nonresponders).
methodsHere we used our measurements of currents in neurons derived from 4 control subjects, 3 patients with BD who were lithium responders, and 3 patients with BD who were nonresponders. We changed the conductances of simulated dentate gyrus and CA3 hippocampal neurons according to our measurements to derive a numerical simulation for BD neurons.
resultsThe computationally simulated BD dentate gyrus neurons had a hyperexcitability phenotype similar to the experimental results. Only the simulated BD CA3 neurons derived from lithium responder patients were hyperexcitable. Interestingly, our computational model captured a physiological instability intrinsic to hippocampal neurons that were derived from nonresponder patients that we also observed when re-examining our experimental results. This instability was caused by a drastic reduction in the sodium current, accompanied by an increase in the amplitude of several potassium currents. These baseline alterations caused nonresponder BD hippocampal neurons to drastically shift their excitability with small changes to their sodium currents, alternating between hyperexcitable and hypoexcitable states.
conclusionsOur computational model of BD hippocampal neurons that was based on our measurements reproduced the experimental phenotypes of hyperexcitability and physiological instability. We hypothesize that the physiological instability phenotype strongly contributes to affective lability in patients with BD.
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