ArticleTranslational psychiatry2017
Polyunsaturated fatty acid deficiency during neurodevelopment in mice models the prodromal state of schizophrenia through epigenetic changes in nuclear receptor genes.
Article in Translational psychiatry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Relevance of diet in schizophrenia: a review focusing on prenatal nutritional deficiency, obesity, oxidative stress and inflammation.Frontiers in nutrition · 2024Pooled it
- Longitudinal investigation of the relationship between omega-3 polyunsaturated fatty acids and neuropsychological functioning in recent-onset psychosis: A randomized clinical trial.Schizophrenia research · 2021Trial
- Maternal fasting during early gestation induces epigenetic alterations and schizophrenia-related phenotypes.Molecular psychiatry · 2026Article
- Reduced serum levels of the pro-resolving lipid mediators resolvin D1 and lipoxin A4 in schizophrenia.Frontiers in psychiatry · 2026Article
- Perinatal omega-3 sex-selectively mitigates neuropsychiatric impacts of prenatal THC in the cortico-striatal-hippocampal circuit.Molecular psychiatry · 2025Article
- The Potential of Hair Matrix for Biomarker Analysis in Schizophrenia.International journal of molecular sciences · 2025Review
- The Impact of Polyunsaturated Fatty Acids in Cancer and Therapeutic Strategies.Current nutrition reports · 2025Review
- Relationships between erythrocyte membrane mono- and poly- unsaturated fatty acid composition and clinical/cognitive indices in antipsychotic-free schizophrenia patients.Frontiers in psychiatry · 2024Article
- Prenatal THC exposure induces long-term, sex-dependent cognitive dysfunction associated with lipidomic and neuronal pathology in the prefrontal cortex-hippocampal network.Molecular psychiatry · 2023Article
- Association between Arachidonic Acid and the Risk of Schizophrenia: A Cross-National Study and Mendelian Randomization Analysis.Nutrients · 2023Article
- Maternal PUFAs, Placental Epigenetics, and Their Relevance to Fetal Growth and Brain Development.Reproductive sciences (Thousand Oaks, Calif.) · 2023Review
- Functional Nutrition as Integrated Intervention for In- and Outpatient with Schizophrenia.Current neuropharmacology · 2023Article
- Combination of Walnut Peptide and Casein Peptide alleviates anxiety and improves memory in anxiety mices.Frontiers in nutrition · 2023Article
- Analysis of polyunsaturated fatty acids in antipsychotic-free individuals with at-risk mental state and patients with first-episode schizophrenia.Frontiers in psychiatry · 2023Article
- The Influence of Acitretin on Brain Lipidomics in Adolescent Mice-Implications for Pediatric and Adolescent Dermatological Therapy.International journal of molecular sciences · 2022Article
- The Role of the Paraventricular-Coerulear Network on the Programming of Hypertension by Prenatal Undernutrition.International journal of molecular sciences · 2022Review
- Repurposing Peroxisome Proliferator-Activated Receptor Agonists in Neurological and Psychiatric Disorders.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Network modules linking expression and methylation in prefrontal cortex of schizophrenia.Epigenetics · 2021Article
- Maternal Supply of Both Arachidonic and Docosahexaenoic Acids Is Required for Optimal Neurodevelopment.Nutrients · 2021Review
- Metabolomic Identification of Exosome-Derived Biomarkers for Schizophrenia: A Large Multicenter Study.Schizophrenia bulletin · 2021Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The risk of schizophrenia is increased in offspring whose mothers experience malnutrition during pregnancy. Polyunsaturated fatty acids (PUFAs) are dietary components that are crucial for the structural and functional integrity of neural cells, and PUFA deficiency has been shown to be a risk factor for schizophrenia. Here, we show that gestational and early postnatal dietary deprivation of two PUFAs-arachidonic acid (AA) and docosahexaenoic acid (DHA)-elicited schizophrenia-like phenotypes in mouse offspring at adulthood. In the PUFA-deprived mouse group, we observed lower motivation and higher sensitivity to a hallucinogenic drug resembling the prodromal symptoms in schizophrenia. Furthermore, a working-memory task-evoked hyper-neuronal activity in the medial prefrontal cortex was also observed, along with the downregulation of genes in the prefrontal cortex involved in oligodendrocyte integrity and the gamma-aminobutyric acid (GABA)-ergic system. Regulation of these genes was mediated by the nuclear receptor genes Rxr and Ppar, whose promoters were hyper-methylated by the deprivation of dietary AA and DHA. In addition, the RXR agonist bexarotene upregulated oligodendrocyte- and GABA-related gene expression and suppressed the sensitivity of mice to the hallucinogenic drug. Notably, the expression of these nuclear receptor genes were also downregulated in hair-follicle cells from schizophrenia patients. These results suggest that PUFA deficiency during the early neurodevelopmental period in mice could model the prodromal state of schizophrenia through changes in the epigenetic regulation of nuclear receptor genes.
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