DNA Methylation in Schizophrenia Subjects: Gender and MTHFR 677C/T Genotype Differences
Open accessAbstract
AIM: In schizophrenia, metabolic syndrome incidence is double that of the general population, with women having a higher incidence. Pharmacogenetically regulated folic acid may be related to this risk. DNA methylation and metabolic syndrome within this group has not been previously studied. METHODS: Metabolic syndrome was evaluated with fasting laboratory measurements, and dietary and lifestyle assessments. Methylation analysis used a peripheral sample for the LINE-1 assay. DNA was also genotyped for MTHFR 677C/T. RESULTS: This analysis included 133 subjects. We found a significant relationship between LINE-1 methylation, and an interaction between MTHFR and gender, controlling for serum folate (p = 0.008). Females with the 677TT genotype had the lowest methylation (56%) compared with the other groups (75%). CONCLUSION: TT genotype females had the lowest methylation, which may explain metabolic syndrome gender differences in schizophrenia. Folate supplementation may be a suggested intervention within schizophrenia; however, additional work is required.
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Previous studies have shown that epigenetics is an important contributor to the sex differences in brain functions and vulnerability to diseases.
“Previous studies have shown that epigenetics is an important contributor to the sex differences in brain functions and vulnerability to diseases [12–16]”
From Sex-specific DNA methylation differences in Alzheimer’s disease pathology (2021) · cites this paper as [15]
The Discussion reports gender differences in DNA methylation among people with schizophrenia and suggests these may contribute to women's higher metabolic-syndrome risk. It explicitly says causality cannot be established. The paper does not show that epigenetics is an established contributor to sex differences in brain function or to disease vulnerability generally. Page numbers were not available in our copy. (LLM, conf=0.86)
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Additional file 2 of Sex-specific DNA methylation differences in Alzheimer’s disease pathology
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Additional file 1 of Sex-specific DNA methylation differences in Alzheimer’s disease pathology
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Ghosh, D., Sadhukhan, S., Attri, M., Singh, T., Debnath, B., & Porel, P. (2026) · Metabolic Brain Disease · doi:10.1007/s11011-026-01904-x
- Authors
- Burghardt, K. J., Pilsner, J. R., Bly, M. J., & Ellingrod, V. L.
- Affiliations
- University of Michigan (US)
- University of Massachusetts Amherst (US)
- Venue
- Epigenomics
- Publisher
- Informa UK Limited
- Published
- 2012-06
- Volume
- 4
- Issue
- 3
- Pages
- 261-268
- ISSN
- 1750-1911 (ISSN-L)
- 1750-192X
- PMC
- PMC3392683
- OpenAlex
- W2089618004
- Cited by
- 49
- References
- 30
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 7 · 2020: 2 · 2018: 3 · 2017: 2 · 2016: 3 · 2015: 6 · 2014: 10 · 2013: 5
- FWCI
- 2.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Epigenomics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH-NCCR (R01 MH082784-01)
- GCRC Program (UL1RR024986)
- Chemistry Core of the Michigan Diabetes Research and Training Center (NIH5P60 DK 20572))
- Washtenaw Community Health Organization
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- schizophrenia, DNA methylation, LINE-1 methylation, MTHFR 677 C>T polymorphism, metabolic syndrome, sex differences, serum folate, folic acid supplementation, pharmacogenetics
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Chlorpromazine, DNA Mutational Analysis, Female, Folic Acid, Genotype, Humans, Male, Middle Aged, Schizophrenia, Sex Factors, Antipsychotic Agents, DNA Methylation, Long Interspersed Nucleotide Elements, Polymorphism, Single Nucleotide, Metabolic Syndrome, Methylenetetrahydrofolate Reductase (NADPH2), Molecular Typing
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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