ArticleTranslational psychiatry2018
Lithium and fluoxetine regulate the rate of phosphoinositide synthesis in neurons: a new view of their mechanisms of action in bipolar disorder.
Article in Translational psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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
17 citing papers in PubMed, 30 citations in OpenAlex.
- Pho84/GLUT2 are cellular myo-inositol exporters regulated by inositol pyrophosphates.The EMBO journal · 2026Article
- Myo-inositol concentration in the medial prefrontal cortex is associated with changes in brain white matter microstructure in early psychosis.Translational psychiatry · 2026Article
- Basic features of cellular inositol metabolism as revealed by a newly developed LC-MS method.The Biochemical journal · 2025Article
- Lithium fine tunes lipid membranes through phospholipid binding.Scientific reports · 2025Article
- Lithium, Inflammation and Neuroinflammation with Emphasis on Bipolar Disorder-A Narrative Review.International journal of molecular sciences · 2024Review
- IMPA1 dependent regulation of phosphatidylinositol 4,5-bisphosphate and calcium signalling by lithium.Life science alliance · 2024Article
- Neuropsychological Characterization of Autosomal Recessive Intellectual Developmental Disorder 59 Associated with IMPA1 (MRT59).Brain sciences · 2023Article
- Inositol monophosphatase 1 (IMPA1) mutation in intellectual disability patients impairs neurogenesis but not gliogenesis.Molecular psychiatry · 2021Article
- Cytoplasmic cleavage of IMPA1 3' UTR is necessary for maintaining axon integrity.Cell reports · 2021Article
- The Role of the UPR Pathway in the Pathophysiology and Treatment of Bipolar Disorder.Frontiers in cellular neuroscience · 2021Review
- MINPP1 prevents intracellular accumulation of the chelator inositol hexakisphosphate and is mutated in Pontocerebellar Hypoplasia.Nature communications · 2020Article
- Mitochondria under the spotlight: On the implications of mitochondrial dysfunction and its connectivity to neuropsychiatric disorders.Computational and structural biotechnology journal · 2020Review
- ITPK1 mediates the lipid-independent synthesis of inositol phosphates controlled by metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Crosstalk between Ras and inositol phosphate signaling revealed by lithium action on inositol monophosphatase in Schizophyllum commune.Advances in biological regulation · 2019Article
- Loss-of-function mutation in inositol monophosphatase 1 (IMPA1) results in abnormal synchrony in resting-state EEG.Orphanet journal of rare diseases · 2019Article
- Phosphoinositides: Regulators of Nervous System Function in Health and Disease.Frontiers in molecular neuroscience · 2019Review
- Modulation of Oxidative Stress: Pharmaceutical and Pharmacological Aspects 2018.Oxidative medicine and cellular longevityArticle
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Lithium is widely used to treat bipolar disorder, but its primary mechanism of action is uncertain. One proposal has been that lithium's ability to inhibit the enzyme inositol monophosphatase (IMPase) reduces the supply of recycled inositol used for membrane phosphoinositide (PIns) synthesis. This 28-year-old hypothesis is still widely debated, however, largely because total levels of PIns in brain or in cultured neurons do not decrease after lithium treatment. Here we use mature cultured cortical neurons to show that, although lithium has little effect on steady-state levels of either inositol or PIns, it markedly inhibits the rate of PIns synthesis. Moreover, we show that rapid synthesis of membrane PIns preferentially uses inositol newly imported from the extracellular space. Unexpectedly, we also find that the antidepressant drug fluoxetine (FLUO: Prozac) stimulates the rate of PIns synthesis. The convergence of both lithium and FLUO in regulating the rate of synthesis of PIns in opposite ways highlights PIns turnover in neurons as a potential new drug target, as well as for understanding mood control in BD. Our results also indicate new avenues for investigation of how neurons regulate their supply of inositol.
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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.