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.

Keywords::

• DNA methylation
• LINE-1
• parvalbumin
• postmortem brain
• schizophrenia

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Financial & competing interests disclosure

HA Fachim has received fellowships from CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) and FAPESP (proc. no. 2017/00624-5). GP Reynolds has received honoraria for lectures and/or advisory panel membership from Janssen, Lundbeck, Otsuka, Sumitomo and Sunovion, and a research grant from Sunovion. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

HA Fachim has received fellowships from CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) and FAPESP (proc. no. 2017/00624-5). GP Reynolds has received honoraria for lectures and/or advisory panel membership from Janssen, Lundbeck, Otsuka, Sumitomo and Sunovion, and a research grant from Sunovion. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.