ArticleEBioMedicine2019
Investigation of betaine as a novel psychotherapeutic for schizophrenia.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 72 citations in OpenAlex.
- Targeted and Untargeted Urinary Metabolomic Analyses of Organophosphate Pesticides Exposure and Attention-Deficit/Hyperactivity Disorder in Children.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Upregulation of DNA repair-related genes in the prefrontal cortex of patients with schizophrenia with low genetic risk.Schizophrenia (Heidelberg, Germany) · 2026Article
- Metabolic Mechanisms in Electroconvulsive Therapy for Schizophrenia: Role, Potential and Future Directions.International journal of molecular sciences · 2026Review
- UntargetedTranslational psychiatry · 2026Article
- Betaine: A Promising Natural Product for Neurological and Psychiatric Diseases.Current neuropharmacology · 2026Review
- Genetic risk for neurodevelopmental disorders as a potential factor affecting antipsychotic responsiveness in schizophrenia: a postmortem brain study.Frontiers in psychiatry · 2026Article
- Elucidating the Complex Etiology of Schizophrenia: Comprehensive Insights into the Therapeutic Roles of Natural Compounds and Pharmacological Interventions.Current pharmaceutical design · 2026Review
- CHDH Promotes Breast Cancer Metastasis Relying on IL17RB/CREB1 Signalling Activation.Journal of cellular and molecular medicine · 2025Article
- The association between plasma betaine level and brain structural changes in schizophrenia.Schizophrenia (Heidelberg, Germany) · 2025Article
- Betaine alleviates deficits in motor behavior, neurotoxic effects, and neuroinflammatory responses in a rat model of demyelination.Toxicology reports · 2025Article
- Chronic corticosterone exposure causes anxiety- and depression-related behaviors with altered gut microbial and brain metabolomic profiles in adult male C57BL/6J mice.Molecular brain · 2024Article
- The effect of phencyclidine-mediated blockade of NMDA receptors in the early postnatal period on glutathione and sulfur amino acid levels in the rat brain as a potential causative factor of schizophrenia-like behavior in adulthood.Pharmacological reports : PR · 2024Article
- Advances in the study of phencyclidine-induced schizophrenia-like animal models and the underlying neural mechanisms.Schizophrenia (Heidelberg, Germany) · 2024Review
- Unveiling the crucial role of betaine: modulation of GABA homeostasis via SLC6A1 transporter (GAT1).Cellular and molecular life sciences : CMLS · 2024Article
- Exploring the Effects of Different Drying Methods on Related Differential Metabolites ofPlants (Basel, Switzerland) · 2024Article
- Article
- Association of homocysteine with white matter dysconnectivity in schizophrenia.Schizophrenia (Heidelberg, Germany) · 2024Article
- Betaine alleviates cognitive impairment induced by homocysteine through attenuating NLRP3-mediated microglial pyroptosis in an mRedox biology · 2024Article
- Determination of Choline-Containing Compounds in Rice Bran Fermented withMass spectrometry (Tokyo, Japan) · 2024Article
- Exploring the Biomarkers and Potential Mechanisms of Botulinum Toxin Type A in the Treatment of Microglial Inflammatory Activation through P2X7 Receptors based on Transcriptome Sequencing.Current pharmaceutical design · 2024Article
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Authors and funding
23 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBetaine is known to act against various biological stresses and its levels were reported to be decreased in schizophrenia patients. We aimed to test the role of betaine in schizophrenia pathophysiology, and to evaluate its potential as a novel psychotherapeutic.
methodsUsing Chdh (a gene for betaine synthesis)-deficient mice and betaine-supplemented inbred mice, we assessed the role of betaine in psychiatric pathophysiology, and its potential as a novel psychotherapeutic, by leveraging metabolomics, behavioral-, transcriptomics and DNA methylation analyses.
findingsThe Chdh-deficient mice revealed remnants of psychiatric behaviors along with schizophrenia-related molecular perturbations in the brain. Betaine supplementation elicited genetic background-dependent improvement in cognitive performance, and suppressed methamphetamine (MAP)-induced behavioral sensitization. Furthermore, betaine rectified the altered antioxidative and proinflammatory responses induced by MAP and in vitro phencyclidine (PCP) treatments. Betaine also showed a prophylactic effect on behavioral abnormality induced by PCP. Notably, betaine levels were decreased in the postmortem brains from schizophrenia, and a coexisting elevated carbonyl stress, a form of oxidative stress, demarcated a subset of schizophrenia with "betaine deficit-oxidative stress pathology". We revealed the decrease of betaine levels in glyoxylase 1 (GLO1)-deficient hiPSCs, which shows elevated carbonyl stress, and the efficacy of betaine in alleviating it, thus supporting a causal link between betaine and oxidative stress conditions. Furthermore, a CHDH variant, rs35518479, was identified as a cis-expression quantitative trait locus (QTL) for CHDH expression in postmortem brains from schizophrenia, allowing genotype-based stratification of schizophrenia patients for betaine efficacy.
interpretationThe present study revealed the role of betaine in psychiatric pathophysiology and underscores the potential benefit of betaine in a subset of schizophrenia. FUND: This study was supported by the Strategic Research Program for Brain Sciences from AMED (Japan Agency for Medical Research and Development) under Grant Numbers JP18dm0107083 and JP19dm0107083 (TY), JP18dm0107129 (MM), JP18dm0107086 (YK), JP18dm0107107 (HY), JP18dm0107104 (AK) and JP19dm0107119 (KH), by the Grant-in-Aid for Scientific Research on Innovative Areas from the MEXT under Grant Numbers JP18H05435 (TY), JP18H05433 (AH.-T), JP18H05428 (AH.-T and TY), and JP16H06277 (HY), and by JSPS KAKENHI under Grant Number JP17H01574 (TY). In addition, this study was supported by the Collaborative Research Project of Brain Research Institute, Niigata University under Grant Numbers 2018-2809 (YK) and RIKEN Epigenetics Presidential Fund (100214-201801063606-340120) (TY).
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