S14. DNA methylation changes in GABAergic and glutamatergic markers in early schizophrenia.

FACHIM, Helene, LOUREIRO, Camila, CORSI-ZUELI, Fabiana, MENEZES, Paulo Rossi, LOUZADA JR, Paulo, DALTON, Caroline, DEL-BEN, Cristina Marta and REYNOLDS, Gavin (2018). S14. DNA methylation changes in GABAergic and glutamatergic markers in early schizophrenia. Schizophrenia Bulletin, 44 (suppl_), S329.

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Link to published version:: https://doi.org/10.1093/schbul/sby018.801
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Abstract

Background: GABAergic and glutamatergic systems play an important role in the neurobiology of schizophrenia, and changes in their markers are reported in both postmortem human brain and in animal models. Recent studies have demonstrated that abnormalities in DNA methylation may underlie the alterations in various indicators of GABAergic and glutamatergic functions in schizophrenia. As our group previously found decreased NR2 protein plasma levels and downregulation of parvalbumin (PVALB) mRNA in first episode of psychosis (FEP) patients, we hypothesised that changes in DNA methylation may be responsible for these indicators of glutamatergic and GABAergic deficits in FEP patients. Methods: Blood samples were collected from patients in FEP (n = 35) after their first contact with the mental health assistance, siblings (n = 21) and population-based controls (n = 35). Bisulfite conversion and pyrosequencing were used to determine methylation levels in 4 CpG sites in promoter sequence of PVALB and 5 CpG sites at GRIN2B (gene which encodes NR2). Results: We found hypermethylation at a CpG site within the PVALB promoter sequence in patients and their siblings compared to population-based control group (p< 0.001) while overall hypomethylation was found in the 5 CpGs analysed within GRIN2B promoter sequence (p < 0.01). Discussion: Our PVALB findings are consistent with our previous studies showing that PVALB promoter methylation is elevated in schizophrenia and, additionally this is the first evidence showing changes in GRIN2B promoter methylation in psychosis. These results together suggest that these epigenetic findings may relate to the reduction of protein expression of indicators of glutamate and GABA systems seen in this disease.

Item Type: Article
Additional Information: Abstracts for the Sixth Biennial SIRS Conference ** From Crossref via Jisc Publications Router. ** Licence for VoR version of this article starting on 01-04-2018: http://creativecommons.org/licenses/by/4.0/
Uncontrolled Keywords: Psychiatry and Mental health
Research Institute, Centre or Group - Does NOT include content added after October 2018: Biomolecular Sciences Research Centre
Identification Number: https://doi.org/10.1093/schbul/sby018.801
Page Range: S329
SWORD Depositor: Margaret Boot
Depositing User: Margaret Boot
Date Deposited: 20 Apr 2018 10:45
Last Modified: 25 Feb 2019 11:30
URI: http://shura.shu.ac.uk/id/eprint/19127

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