ArticleMolecular psychiatry2023
GWAS-identified bipolar disorder risk allele in the FADS1/2 gene region links mood episodes and unsaturated fatty acid metabolism in mutant mice.
Article in Molecular psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
- Cell-type-specific genetic architecture reveals neuronal and immune contributions to neuropsychiatric disorders.Molecular psychiatry · 2026Article
- Next-generation precision medicine for mood disorders: reproducible blood biomarkers enable objective diagnostics, subtyping, and targeted therapeutics.Molecular psychiatry · 2026Article
- Mendelian-Randomization Study Reveals Causal Relationships Between Blood Metabolites and Psychiatric Disorders.Schizophrenia bulletin · 2026Article
- Single-cell transcriptome-wide Mendelian randomization during CD4Communications biology · 2026Article
- FADS1 contributes to anesthesia/surgery-induced cognitive impairment by aggravating omega-6 fatty acid metabolic disruption in aged mice.Journal of neuroinflammation · 2026Article
- Molecular and Neuroimaging Correlates of Bipolar Disorder: Linking Inflammation, Mitochondria, and Brain Circuitry.International journal of molecular sciences · 2026Review
- Polyunsaturated fatty acids and psychotic disorders: integrating mechanistic, genetic, and clinical evidence.Frontiers in nutrition · 2026Review
- Artificial Intelligence-Based Methods and Omics for Mental Illness Diagnosis: A Review.Bioengineering (Basel, Switzerland) · 2025Review
- Bidirectional causal associations between plasma metabolites and bipolar disorder.Molecular psychiatry · 2025Article
- Bta-novel-miR-25336 enhanced adipose differentiation and unsaturated fatty acid synthesis by targeting ACADS in intramuscular adipocytes of river buffalo.BMC genomics · 2025Article
- Epigenetic regulation of iron metabolism and ferroptosis in Parkinson's disease: Identifying novel epigenetic targets.Acta pharmacologica Sinica · 2025Review
- Quantitative trait loci mapping of circulating metabolites in cerebrospinal fluid to uncover biological mechanisms involved in brain-related phenotypes.Molecular psychiatry · 2025Article
- Ferroptosis as a potential molecular mechanism of bipolar disorder.Translational psychiatry · 2025Review
- The Association Among Bipolar Disorder, Mitochondrial Dysfunction, and Reactive Oxygen Species.Biomolecules · 2025Review
- NEK4 modulates circadian fluctuations of emotional behaviors and synaptogenesis in male mice.Nature communications · 2024Article
- Lack of evidence for GWAS signals of exfoliation glaucoma working via monogenic loss-of-function mutation in the nearest gene.Human molecular genetics · 2024Article
- Sex-Specific Changes to Brain Fatty Acids, Plasmalogen, and Plasma Endocannabinoids in Offspring Exposed to Maternal and Postnatal High-Linoleic-Acid Diets.International journal of molecular sciences · 2024Article
- Exploring the dynamic three-dimensional chromatin architecture and transcriptional landscape in goose liver tissues underlying metabolic adaptations induced by a high-fat diet.Journal of animal science and biotechnology · 2024Article
- Genomic SEM applied to explore etiological divergences in bipolar subtypes.Psychological medicine · 2024Article
- Shared genetic basis informs the roles of polyunsaturated fatty acids in brain disorders.medRxiv : the preprint server for health sciences · 2023Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Large-scale genome-wide association studies (GWASs) on bipolar disorder (BD) have implicated the involvement of the fatty acid desaturase (FADS) locus. These enzymes (FADS1 and FADS2) are involved in the metabolism of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are thought to potentially benefit patients with mood disorders. To model reductions in the activity of FADS1/2 affected by the susceptibility alleles, we generated mutant mice heterozygously lacking both Fads1/2 genes. We measured wheel-running activity over six months and observed bipolar swings in activity, including hyperactivity and hypoactivity. The hyperactivity episodes, in which activity was far above the norm, usually lasted half a day; mice manifested significantly shorter immobility times on the behavioral despair test performed during these episodes. The hypoactivity episodes, which lasted for several weeks, were accompanied by abnormal circadian rhythms and a marked decrease in wheel running, a spontaneous behavior associated with motivation and reward systems. We comprehensively examined lipid composition in the brain and found that levels of certain lipids were significantly altered between wild-type and the heterozygous mutant mice, but no changes were consistent with both sexes and either DHA or EPA was not altered. However, supplementation with DHA or a mixture of DHA and EPA prevented these episodic behavioral changes. Here we propose that heterozygous Fads1/2 knockout mice are a model of BD with robust constitutive, face, and predictive validity, as administration of the mood stabilizer lithium was also effective. This GWAS-based model helps to clarify how lipids and their metabolisms are involved in the pathogenesis and treatment of BD.
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