ArticleMolecular psychiatry2026
Modulation of neuronal excitability and plasticity by BHLHE41 conveys lithium non-responsiveness.
Article in Molecular psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
- New Genomics Discoveries Across the Bipolar Disorder Spectrum Implicate Neurobiological and Developmental Pathways.Biological psychiatry · 2025Review
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20 authors.
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Abstract
Many bipolar disorder (BD) patients are non-responsive to lithium. The mechanisms underlying lithium (non-)responsiveness are largely unknown. By using gene-set enrichment analysis methods, we found that core clock gene-sets are significantly associated with lithium response. Among the top hits was BHLHE41, a modulator of the molecular clock and homeostatic sleep. Since BHLHE41 and its paralog BHLHE40 are functionally redundant, we assessed chronic lithium response in double-knockout mutant mice (DKO). We demonstrated that DKOs are non-responsive to lithium's effect in various behavioral tasks. Cellular assays and patch clamp recordings revealed lowered excitability and reduced lithium-response in prefrontal cortical layer 2/3 DKO neurons and on hippocampal long-term potentiation. Single-cell RNA sequencing identified that lithium deregulated mitochondrial respiration, cation channel and postsynapse associated gene-sets specifically in upper layer excitatory neurons. Our findings show that lithium acts in a highly cell-specific way on neuronal metabolism and excitability and modulates synaptic plasticity depending on BHLHE40/41.
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Registered trials
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