Association between CpG island DNA methylation in the promoter region of RELN and positive and negative types of schizophrenia
Open accessAbstract
Objective To explore the association between CpG island methylation in the promoter region of RELN and positive (type I) and negative (type II) types of schizophrenia, and investigate serum interleukin (IL)-1β, IL-6, and myelin basic protein (MBP) in schizophrenia. Methods Levels of CpG island methylation in the promoter region of RELN were detected in peripheral blood of patients with schizophrenia (experimental group) and healthy individuals (control group), and serum IL-1β, IL-6, and MBP were measured. Results The positive rate of CpG island methylation in the promoter region of RELN was higher in the experimental group than in the control group; however, there were no significant differences between type I and II patients. There were differences in Positive and Negative Syndrome Scale (PANSS) scores and serum IL-1β, IL-6, and MBP between type I and II patients. Furthermore, there were positive correlations between serum IL-1β, IL-6, and MBP and PANSS scores (negative symptoms) in type II patients. Conclusion CpG island methylation in the promoter region of RELN was associated with schizophrenia, but not with its clinical type. There may be different pathological mechanisms in type I and II schizophrenia, and type II schizophrenia may be associated with serum IL-1β, IL-6, and MBP.
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In schizophrenia, RELN hypermethylation reduces reelin expression and disrupts synaptic plasticity and neuronal migration.
“Studies in schizophrenia show that RELN hypermethylation reduces reelin expression and disrupts synaptic plasticity and neuronal migration”
From The clinical use of epigenetics in psychiatry: a narrative review of epigenetic mechanisms, key candidate genes, and precision psychiatry (2025) · cites this paper as [15]
The Introduction (page unavailable) says RELN methylation affects expression, is more severe when RELN is silenced, and describes reelin’s roles in synaptic plasticity and neuronal migration. The Discussion (page unavailable) reports higher RELN promoter methylation in patients with schizophrenia. Neither section establishes that hypermethylation disrupts synaptic plasticity or neuronal migration in those patients; the claimed causal chain is stronger than the paper’s findings. (LLM, conf=0.85)
Experimental — accuracy not yet measuredIn schizophrenia, COMT methylation alters dopamine metabolism.
“COMT methylation alters dopamine metabolism”
From The clinical use of epigenetics in psychiatry: a narrative review of epigenetic mechanisms, key candidate genes, and precision psychiatry (2025) · cites this paper as [15]
The Discussion reports RELN promoter methylation in schizophrenia and mentions dopaminergic neuron development, but it does not address COMT or dopamine metabolism. Searches for COMT methylation and catechol-O-methyltransferase found no passage supporting the attributed claim. (LLM, conf=0.77)
Experimental — accuracy not yet measuredIn schizophrenia, BDNF methylation is associated with cognitive impairment and negative symptoms.
“BDNF methylation is associated with cognitive impairment and negative symptoms”
From The clinical use of epigenetics in psychiatry: a narrative review of epigenetic mechanisms, key candidate genes, and precision psychiatry (2025) · cites this paper as [15]
The Introduction (page unavailable) identifies RELN promoter methylation, not BDNF methylation, as the study’s focus. The Results (page unavailable) link IL-1β, IL-6, and MBP—not BDNF—to negative-symptom scores. Searches for BDNF and brain-derived neurotrophic factor found no passage linking BDNF methylation to cognitive impairment or negative symptoms. (LLM, conf=0.76)
Experimental — accuracy not yet measured
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Cites
von Elm, E., Altman, D. G., Egger, M., Pocock, S. J., Gøtzsche, P. C., Vandenbroucke, J. P., & Initiative, F. T. S. (2007) · Annals of Internal Medicine · doi:10.7326/0003-4819-147-8-200710160-00010 · Cited by 17,796 · see citing works
Negative v Positive Schizophrenia
Andreasen, N. C. (1982) · Archives of General Psychiatry · doi:10.1001/archpsyc.1982.04290070025006 · Cited by 2,008 · see citing works
Reelin promoter hypermethylation in schizophrenia
Grayson, D. R., Jia, X., Chen, Y., Sharma, R. P., Mitchell, C. P., Guidotti, A., & Costa, E. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503736102 · Cited by 553 · see citing works
Abdolmaleky, H. M., Cheng, K., Russo, A. L., Smith, C. L., Faraone, S. V., Wilcox, M., Shafa, R., Glatt, S. J., Nguyen, G. H., Ponte, J. F., et al. (2005) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30140 · Cited by 390 · see citing works
Positive vs. Negative Schizophrenia: A Critical Evaluation
Andreasen, N. C. (1985) · Schizophrenia Bulletin · doi:10.1093/schbul/11.3.380 · Cited by 331 · see citing works
Molecular links between endocrine, nervous and immune system during chronic stress
Zefferino, R., Di Gioia, S., & Conese, M. (2021) · Brain and Behavior · doi:10.1002/brb3.1960 · Cited by 204 · see citing works
Kunz, M., Ceresér, K. M. M., Goi, P. D., Fries, G. R., Teixeira, A. L., Fernandes, B. S., Belmonte-de-Abreu, P. S., Kauer‐Sant’Anna, M., Kapczinski, F. P., & Gama, C. S. (2011) · Brazilian Journal of Psychiatry · doi:10.1590/s1516-44462011000300010 · Cited by 189 · see citing works
Boerrigter, D., Weickert, T. W., Lenroot, R., O׳Donnell, M., Galletly, C. A., Liu, D., Burgess, M., Cadiz, R., Jacomb, I., Catts, V. S., et al. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0962-y · Cited by 171 · see citing works
A differential role for interleukin-6 and tumor necrosis factor-α in schizophrenia?
Naudin, J., Capo, C., Giusano, B., Mège, J. L., & Azorin, J. (1997) · Schizophrenia Research · doi:10.1016/s0920-9964(97)00059-5 · Cited by 141 · see citing works
Evaluation of positive and negative symptoms in schizophrenia
Andreasen, N. C., & Grove, W. M. (1986) · Psychiatry and Psychobiology · doi:10.1017/s0767399x00003199 · Cited by 120 · see citing works
Elevated circulating levels of IL-6 in schizophrenia
Naudin, J., Mège, J. L., Azorin, J., & Dassa, D. (1996) · Schizophrenia Research · doi:10.1016/0920-9964(96)00014-x · Cited by 104 · see citing works
Cytokine Imbalance in Schizophrenia. From Research to Clinic: Potential Implications for Treatment
Reale, M., Costantini, E., & Greig, N. H. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.536257 · Cited by 98 · see citing works
Garriga, J., Laumet, G. O., Chen, S.-R., Zhang, Y., Madžo, J., Issa, J. J., Pan, H., & Jelı́nek, J. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.2616-17.2018 · Cited by 94 · see citing works
The Genetic Variation of RELN Expression in Schizophrenia and Bipolar Disorder
Ovadia, G., & Shifman, S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019955 · Cited by 79 · see citing works
Reelin (RELN) DNA methylation in the peripheral blood of schizophrenia
Nabil Fikri, R. M., Norlelawati, A. T., Nour El-Huda, A. R., Hanisah, M. N., Kartini, A., Norsidah, K., & Nor Zamzila, A. (2017) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2016.12.020 · Cited by 61 · see citing works
Nishikawa, S., Goto, S., Yamada, K., Hamasaki, T., & Ushio, Y. (2003) · The Journal of Comparative Neurology · doi:10.1002/cne.10610 · Cited by 58 · see citing works
Reduced Myelin Basic Protein and Actin-Related Gene Expression in Visual Cortex in Schizophrenia
Matthews, P., Eastwood, S. L., & Harrison, P. J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0038211 · Cited by 55 · see citing works
Rodrígues-Amorím, D., Baltanás, T. R., Vallejo-Curto, M. D. C., Rodríguez-Jamardo, C., Heras, E. D. L., Barreiro-Villar, C., Blanco-Formoso, M., Fernández-Palleiro, P., Álvarez-Ariza, M., López, M., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-71060-4 · Cited by 44 · see citing works
The Effects of Exercise on IL-6 Levels and Cognitive Performance in Patients with Schizophrenia
Gómez-Rubio, P., & Trapero, I. (2019) · Diseases · doi:10.3390/diseases7010011 · Cited by 43 · see citing works
Parlapani, E., Schmitt, A., Erdmann, A., Bernstein, H., Breunig, B., Gruber, O., Petroianu, G. A., von Wilmsdorff, M., Schneider-Axmann, T., Honer, W. G., et al. (2009) · Brain Research · doi:10.1016/j.brainres.2009.09.007 · Cited by 38 · see citing works
Uranova, N. A., Бонарцев, П. Д., Андросова, Л. В., Рахманова, В. И., & Каледа, В. Г. (2017) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-017-0782-1 · Cited by 30 · see citing works
Dai, N., Jie, H., Duan, Y., Xiong, P., Xu, X., Peng, C., Kang, M., Li, M., Li, T., Huang, Z., et al. (2020) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.13078 · Cited by 26 · see citing works
Ogino, H., Nakajima, T., Hirota, Y., Toriuchi, K., Aoyama, M., Nakajima, K., & Hattori, M. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.0125-20.2020 · Cited by 20 · see citing works
Bohnert, S., Wirth, C. T., Schmitz, W., Trella, S., Monoranu, C., Ondruschka, B., & Bohnert, M. (2021) · International Journal of Legal Medicine · doi:10.1007/s00414-021-02606-y · Cited by 20 · see citing works
Igg‐Dependent Hydrolysis of Myelin Basic Protein of Patients with Different Courses of Schizophrenia
Parshukova, D. A., Smirnova, L. P., Kornetova, E. G., Semke, A. V., Buneva, V. N., & Ivanova, S. А. (2020) · Journal of Immunology Research · doi:10.1155/2020/8986521 · Cited by 16 · see citing works
Serum immunological parameters as markers of remission quality in schizophrenia
Kostyuk, G. P., Галкина, А. Ю., Karpenko, O., & Golubev, A. (2019) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2018.11.469 · Cited by 3 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- [10]Yan T Cheng C Wang H, et al. Detection and significance of serum interleukin-6, tumor necrosis factor-α and interleukin-1β in first-episode schizophrenia patients. J Hainan Med Univ 2015; 21: 1106– 1108. Doi:10.13210/j.cnki.jhmu.20150120.001. · DOI
- [14]Singh A Singh K Sahu A, et al. Serum concentration of myelin basic protein as a prognostic marker in mild-to-moderate head injury patients: a prospective study in a tertiary care center. Indian J Neurosurg 2021: 1– 5. doi: 10.1055/s-0040-1716936.34798610 · DOI
- [20]Yang Y Song ZW Han L, et al. Detection of peripheral blood reelin gene methylation in patients with first-episode schizophrenia. Lab Med Clin 2015; 12: 3373– 3375.
Cited by
Sorted by citations
Reelin Signaling in Neurodevelopmental Disorders and Neurodegenerative Diseases
Joly‐Amado, A., Kulkarni, N., & Nash, K. R. (2023) · Brain Sciences · doi:10.3390/brainsci13101479 · Cited by 43 · see citing works
Ermakov, E. A., Melamud, M. M., Boiko, A. S., Kamaeva, D. A., Ivanova, S. А., Nevinsky, G. A., & Buneva, V. N. (2023) · Brain Sciences · doi:10.3390/brainsci13050836 · Cited by 32 · see citing works
Methylation of melatonin receptors in patients with unipolar and bipolar depression
Lesicka, M., Dmitrzak‐Węglarz, M., Jabłońska, E., Wieczorek, E., Kapelski, P., Szczepankiewicz, A., Pawlak, J., & Reszka, E. (2023) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2023.111776 · Cited by 17 · see citing works
Flynn, L. T., & Gao, W. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02235-4 · Cited by 15 · see citing works
Valderrama-Mantilla, A. I., Martín-Cuevas, C., Gómez-Garrido, A., Morente-Montilla, C., Crespo‐Facorro, B., & García-Cerro, S. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106032 · Cited by 12 · see citing works
Lv, Y., Wen, L., Hu, W.-J., Deng, C., Ren, H., Bao, Y.-N., Su, B.-W., Gao, P., Man, Z., Luo, Y.-Y., et al. (2023) · Metabolic Brain Disease · doi:10.1007/s11011-023-01271-x · Cited by 12 · see citing works
Montel Hayes, R., Mason, C. E., & Miller, J. J. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1671122 · Cited by 5 · see citing works
DNA methylation and schizophrenia – the role in pathogenesis and the diagnosis of the disease
Płaza, O., & Szulc, A. (2022) · Pharmacotherapy in Psychiatry and Neurology · doi:10.5114/fpn.2022.117702 · Cited by 1 · see citing works
The role of inflammatory immunomodulators in the development of schizophrenia
Аршинова, Е. С., Karpova, N. S., Сандомирский, К. А., Нурбеков, М. К., & Архипов, А. Ю. (2023) · Nauchno-prakticheskii zhurnal «Patogenez» · doi:10.25557/2310-0435.2023.03.46-49
- Authors
- Zhou, J., Zhou, D., Yan, T., Chen, W., Xie, H., & Xiong, Y.
- Affiliations
- Medical Service, The Second People’s Hospital of Lishui, Lishui, China
- Department of Clinical Laboratory, The Second People’s Hospital of Lishui, Lishui, China
- Corresponding author
- Xiong, Yan
- Venue
- Journal of International Medical Research
- Publisher
- SAGE Publications
- Published
- 2022-05
- Volume
- 50
- Issue
- 5
- Pages
- 3000605221100345-3000605221100345
- ISSN
- 0300-0605 (ISSN-L)
- 1473-2300
- PMC
- PMC9160895
- OpenAlex
- W4281709318
- Cited by
- 9
- References
- 26
- Citations by year
- 2025: 2 · 2023: 6 · 2022: 1
- FWCI
- 1.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of International Medical Research (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- schizophrenia, reelin, CpG island methylation, DNA methylation, IL-1β, interleukin-6, myelin basic protein, negative symptoms, PANSS
- MeSH terms
- Reelin Protein, Humans, Promoter Regions, Genetic, Schizophrenia, Interleukin-6, CpG Islands, DNA Methylation
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