Global DNA hypomethylation and its correlation to the betaine level in peripheral blood of patients with schizophrenia

Murata, Y.; Ikegame, Tempei; Koike, Shinsuke; Takeo, Satoshi; Ikeda, Masashi; Sasaki, Tsukasa; Iwata, Nakao; Kasai, Kiyoto; Bundo, Miki; Iwamoto, Kazuya

doi:10.1016/j.pnpbp.2019.109855

Cited by 21 publications

(19 citation statements)

References 44 publications

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“…Global DNA hypomethylation is frequently reported in blood cells of psychiatric disorders, including BD 39-41 . We also reported global DNA hypomethylation in BD and SZ in blood cells, and hypomethylation was associated with the serum level of the methyl-group donor betaine ( N,N,N -trimethylglycine) 42 . Whether hypomethylation in the PFC of BD patients is accompanied by similar metabolite changes remains unclear.…”

Section: Discussionmentioning

confidence: 77%

Decreased DNA methylation at promoters and gene-specific neuronal hypermethylation in the prefrontal cortex of patients with bipolar disorder

Bundo

Ueda

Nakachi

et al. 2020

Preprint

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Bipolar disorder (BD) is a severe mental disorder characterized by repeated mood swings. Although genetic factors are collectively associated with the etiology of BD, the underlying molecular mechanisms, particularly how environmental factors affect the brain, remain largely unknown. We performed promoter-wide DNA methylation analysis of neuronal and nonneuronal nuclei in the prefrontal cortex of patients with BD (N=34) and controls (N=35). We found decreased DNA methylation at promoters in both cell types in the BD patients compared to the controls. Gene Ontology (GO) analysis of differentially methylated region (DMR)-associated genes revealed enrichment of molecular motor-related genes in neurons, chemokines in both cell types, and ion channel- and transporter-related genes in nonneurons. Detailed analysis further revealed that growth cone- and dendrite-related genes, including NTRK2 and GRIN1, were hypermethylated in neurons of BD patients. To assess the effect of medication, neuroblastoma cells were cultured under therapeutic concentrations of three different mood stabilizers (lithium, valproate, and carbamazepine). We observed that up to 37.9% of DMRs detected in BD overlapped with mood stabilizer-induced DMRs. Interestingly, mood stabilizer-induced DMRs showed the opposite direction of changes in DMRs in BD, suggesting the therapeutic effects of mood stabilizers on DNA methylation. Among the DMRs, 12 overlapped with loci identified by a previous genome-wide association study of BD. Finally, we performed qPCR analysis of 10 DNA methylation-related genes and found that DNMT3B was overexpressed in BD. The cell type-specific DMRs identified in this study will be useful for understanding the pathophysiology of BD.

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Section: Discussionmentioning

confidence: 77%

Decreased DNA methylation at promoters and gene-specific neuronal hypermethylation in the prefrontal cortex of patients with bipolar disorder

Bundo

Ueda

Nakachi

et al. 2020

Preprint

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“…Betaine has been shown to induce resilience to anhedonia (the inability to feel pleasure) in mice subjected to chronic social defeat stress indicating that betaine could be used as a prophylactic nutrient to prevent stress-related psychiatric disorders [ 218 ]. Decreased circulating plasma levels of betaine were also reported in patients with schizophrenia and bipolar disorder [ 219 ]. Perhaps these disorders could be treated by restoring the depleted levels given the neuroprotective role of betaine [ 210 ].…”

Section: Other Beneficial Effects Of Betainementioning

confidence: 99%

Beneficial Effects of Betaine: A Comprehensive Review

Arumugam

Paal

Donohue

et al. 2021

Biology

113

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Medicinal herbs and many food ingredients possess favorable biological properties that contribute to their therapeutic activities. One such natural product is betaine, a stable, nontoxic natural substance that is present in animals, plants, and microorganisms. Betaine is also endogenously synthesized through the metabolism of choline or exogenously consumed through dietary intake. Betaine mainly functions as (i) an osmolyte and (ii) a methyl-group donor. This review describes the major physiological effects of betaine in whole-body health and its ability to protect against both liver- as well as non-liver-related diseases and conditions. Betaine’s role in preventing/attenuating both alcohol-induced and metabolic-associated liver diseases has been well studied and is extensively reviewed here. Several studies show that betaine protects against the development of alcohol-induced hepatic steatosis, apoptosis, and accumulation of damaged proteins. Additionally, it can significantly prevent/attenuate progressive liver injury by preserving gut integrity and adipose function. The protective effects are primarily associated with the regulation of methionine metabolism through removing homocysteine and maintaining cellular SAM:SAH ratios. Similarly, betaine prevents metabolic-associated fatty liver disease and its progression. In addition, betaine has a neuroprotective role, preserves myocardial function, and prevents pancreatic steatosis. Betaine also attenuates oxidant stress, endoplasmic reticulum stress, inflammation, and cancer development. To conclude, betaine exerts significant therapeutic and biological effects that are potentially beneficial for alleviating a diverse number of human diseases and conditions.

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“…Third, we were unable to assess the genetic contribution to the results of this study. Biomarkers from blood collections, such as the polygenetic risk score 35 may be more useful as a trait marker, and DNA methylation 36 , 37 , RNA-seq 38 , and blood metabolism 37 , 39 may be more useful as state markers.…”

Section: Discussionmentioning

confidence: 99%

Surface area in the insula was associated with 28-month functional outcome in first-episode psychosis

et al. 2021

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Many studies have tested the relationship between demographic, clinical, and psychobiological measurements and clinical outcomes in ultra-high risk for psychosis (UHR) and first-episode psychosis (FEP). However, no study has investigated the relationship between multi-modal measurements and long-term outcomes for >2 years. Thirty-eight individuals with UHR and 29 patients with FEP were measured using one or more modalities (cognitive battery, electrophysiological response, structural magnetic resonance imaging, and functional near-infrared spectroscopy). We explored the characteristics associated with 13- and 28-month clinical outcomes. In UHR, the cortical surface area in the left orbital part of the inferior frontal gyrus was negatively associated with 13-month disorganized symptoms. In FEP, the cortical surface area in the left insula was positively associated with 28-month global social function. The left inferior frontal gyrus and insula are well-known structural brain characteristics in schizophrenia, and future studies on the pathological mechanism of structural alteration would provide a clearer understanding of the disease.

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Global DNA hypomethylation and its correlation to the betaine level in peripheral blood of patients with schizophrenia

Cited by 21 publications

References 44 publications

Decreased DNA methylation at promoters and gene-specific neuronal hypermethylation in the prefrontal cortex of patients with bipolar disorder

Decreased DNA methylation at promoters and gene-specific neuronal hypermethylation in the prefrontal cortex of patients with bipolar disorder

Beneficial Effects of Betaine: A Comprehensive Review

Surface area in the insula was associated with 28-month functional outcome in first-episode psychosis

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