Parvalbumin Promoter Hypermethylation in Postmortem Brain in Schizophrenia
Abstract
Deficits of brain parvalbumin (PV) are a consistent finding in schizophrenia and models of psychosis. We investigated whether this is associated with abnormal PV gene (PVALB) methylation in the brain in schizophrenia. Bisulfite pyrosequencing was used to determine cytosine (CpG) methylation in a PVALB promoter sequence. Greater PVALB methylation was found in schizophrenia hippocampus, while no differences were observed in prefrontal cortex. LINE-1 methylation, a measure of global methylation, was also elevated in both regions in schizophrenia, although the PVALB change was independent of this effect. These results provide the first evidence that PVALB promoter methylation is abnormal in schizophrenia and suggest that this epigenetic finding may relate to the reduction of PV expression seen in the disease.
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In SCZ and psychosis, candidate gene studies across tissues support DNAm differences between cases and controls in PVALB, GMR2 and GMR5, various CpG sites in GABRB2, and GRIN2B.
“In SCZ and psychosis, there is evidence from candidate genes studies across tissues supporting DNAm differences between cases and controls in genes such as the Parvalbumin (PVALB) gene(Fachim, Srisawat, Dalton, & Reynolds, 2018), GMR2 and GMR5 of the glutamatergic receptors (Kordi-Tamandani, Dahmardeh, & Torkamanzehi, 2013a); various CpG sites in the β2 subunit of the GABAa receptor gene (GABRB2)”
From Can epigenetics shine a light on the biological pathways underlying major mental disorders? (2022) · cites this paper as Fachim, Srisawat, Dalton, & Reynolds, 2018
In schizophrenia, PVALB mRNA levels are lower in the hippocampus and in layer 4 of the dorsolateral prefrontal cortex, and DNA hypermethylation may partly account for this.
“In schizophrenia, lower levels of PVALB mRNA, the gene coding for PV, were seen in the hippocampus and layer 4 of the dorsolateral prefrontal cortex, which might be partially explained by DNA hypermethylation [1,8].”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [8]
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References 34 · Cited by 41
- Authors
- Fachim, H. A., Srisawat, U., Dalton, C. F., & Reynolds, G. P.
- Affiliations
- Sheffield Hallam University (GB)
- Venue
- Epigenomics
- Publisher
- Informa UK Limited
- Published
- 2018-04-24
- Volume
- 10
- Issue
- 5
- Pages
- 519-524
- ISSN
- 1750-1911 (ISSN-L)
- 1750-192X
- OpenAlex
- W2801630890
- Cited by
- 41
- References
- 34
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2023: 2 · 2022: 9 · 2021: 8 · 2020: 7 · 2019: 7 · 2018: 1
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Epigenomics (publishedVersion)
- PubMed (publishedVersion)
- SHURA (Sheffield Hallam University Research Archive) (Sheffield Hallam University) (acceptedVersion)
- Funders
- CNPq (2017/00624-5)
- 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 › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Keywords
- parvalbumin, DNA methylation, schizophrenia, hippocampus, prefrontal cortex, LINE-1 methylation, global DNA methylation, epigenetics, postmortem brain
- MeSH terms
- Adult, Aged, Female, Hippocampus, Humans, Male, Middle Aged, Parvalbumins, Promoter Regions, Genetic, Schizophrenia, Prefrontal Cortex, CpG Islands, DNA Methylation, Long Interspersed Nucleotide Elements, Epigenesis, Genetic
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