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Global hypomethylation of peripheral leukocyte DNA in male patients with schizophrenia: A potential link between epigenetics and schizophrenia
Abstract
Genetic and epigenetic factors can potentially alter susceptibility to psychiatric disorders such as schizophrenia. In order to explore the effect of epigenetics on the pathogenesis of schizophrenia, we examined the global methylation level of leukocyte DNA from 210 patients with schizophrenia (124 males and 86 females) and 237 healthy subjects (108 males and 129 females). Methylated deoxycytidine (mC) content in peripheral leukocyte DNA was measured by high performance liquid chromatography (HPLC). We confirmed in the healthy subjects our previous finding that there are sex-dependent differences in mC content (males>females; beta=0.319, p<0.001), in addition to the effect of age (beta=-0.141, p=0.022). We therefore used multiple regression to analyze the data from all subjects by sex, with age as a co-variant. In males, a tendency was observed toward lower mC content in patients than in controls (beta=-0.115, p=0.075), with a significant effect of age (beta=-0.212, p<0.001). This difference was more prominent in younger individuals. In females, no effect of age or disease status on mC content was observed. These results established that there is significant sex-dependent difference in the mC content of human peripheral leukocyte DNA, and raise the possibility that alterations in DNA methylation state are present in patients with schizophrenia.
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“In both human and animal models, it has been observed treatment with haloperidol induces sex-specific DNA methylation differences [71, 72].”
From Sex-specific DNA methylation differences in Alzheimer’s disease pathology (2021) · cites this paper as [72]
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Transcriptome Analysis of Systems Biology for Schizophrenia
Huang, K.-C., Tsao, T. T.-H., Wang, T., & Lee, S. (2016) · InTech eBooks · doi:10.5772/66864 · Cited by 1
DNA Methylation Analysis: Providing New Insight into Human Disease
Cottrell, S. E., deVos, T., Distler, J., Haefliger, C., Lesche, R., Plum, A., & Schuster, M. (2009) · Elsevier eBooks · doi:10.1016/b978-0-12-369420-1.00011-1 · Cited by 1
Epigenetic involvement in psychiatric disorders and psychiatric drugs
de Jong, N. M. (2010) · Utrecht University Repository (Utrecht University)
Epigenetic Epidemiology of Psychiatric Disorders
Uddin, M., Bustamante, A. C., & Toyokawa, S. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-417114-5.00006-1
Epigenomics in Neurobehavioral Diseases
Smith, C. L., & Huang, K. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-388415-2.00007-x
Metadata
- Authors
- Shimabukuro, M., Sasaki, T., Imamura, A., Tsujita, T., Fuke, C., Umekage, T., Tochigi, M., Hiramatsu, K., Miyazaki, T., Oda, T., Sugimoto, J., Jinno, Y., & Okazaki, Y.
- Affiliations
- University of the Ryukyus (JP)
- The University of Tokyo (JP)
- Nagasaki University (JP)
- Mie University (JP)
- Corresponding author
- Jinno, Yoshihiro
- Venue
- Journal of Psychiatric Research
- Publisher
- Elsevier BV
- Published
- 2007-12
- Volume
- 41
- Issue
- 12
- Pages
- 1042-1046
- ISSN
- 0022-3956 (ISSN-L)
- OpenAlex
- W2148944032
- Cited by
- 108
- References
- 40
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 6 · 2016: 10 · 2015: 7 · 2014: 8 · 2013: 5 · 2012: 14
- FWCI
- 2.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychiatric Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- schizophrenia, DNA methylation, global hypomethylation, peripheral blood leukocytes, epigenetics, sex differences, age effects
- MeSH terms
- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Child, Chromatography, High Pressure Liquid, Female, Humans, Leukocytes, Male, Middle Aged, Schizophrenia, Sex Factors, DNA Methylation, Epigenesis, Genetic
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