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Exploring DNA methylation within the CYP17A gene as a potential mediator between childhood adversity and stress-related phenotypes in schizophrenia

Published online by Cambridge University Press:  01 September 2022

M. Alfimova ,
N. Kondratyev ,
A. Golov ,
M. Gabaeva ,
V. Plakunova  and
V. Golimbet
M. Alfimova
Affiliation:
Mental Health Research Center, Clinical Genetics Laboratory, Moscow, Russian Federation
N. Kondratyev
Affiliation:
Mental Health Research Center, Clinical Genetics Laboratory, Moscow, Russian Federation
A. Golov
Affiliation:
Mental Health Research Center, Clinical Genetics Laboratory, Moscow, Russian Federation
M. Gabaeva
Affiliation:
Mental Health Research Center, Clinical Genetics Laboratory, Moscow, Russian Federation
V. Plakunova
Affiliation:
Mental Health Research Center, Clinical Genetics Laboratory, Moscow, Russian Federation
V. Golimbet*
Affiliation:
Mental Health Research Center, Clinical Genetics Laboratory, Moscow, Russian Federation
*
*Corresponding author.

Abstract

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Introduction

Stress caused by childhood adversity (CA) is known to contribute to schizophrenia risk and symptoms. Its effects might be mediated by epigenetic mechanisms, specifically DNA methylation (meDNA) within relevant genes, and predominantly influence the hippocampus and prefrontal cortex (PFC). CYP17A1 is a candidate, as it situates within a schizophrenia risk locus and is involved in glucocorticoid synthesis.

Objectives

To explore meDNA within CYP17A and its relations to hippocampus- and PFC-dependent schizophrenia symptoms: depression and deficits of declarative memory and executive functions.

Methods

We assessed meDNA at each CpG within a CYP17A fragment (chr10:104594471-104595887, hg19) in blood of 66 schizophrenia patients using the third-generation sequencing. Immediate memory, depression, cognitive shifting and cognitive inhibition (CI) were assessed with the RAVLT, PANSS, TMT-B and Stroop word-color test, respectively. ANCOVA and regression models adjusted for sex and age were applied to explore the relations between the phenotypes, local haplotype, meDNA and CA, defined as the presence of parental alcoholism or psychiatric illness.

Results

MeDNA at CpG-SNP rs3781286 correlated with CI (corrected p=0.01). However, there were no main or interaction effects of CA either on meDNA at this site or on CI. Both CI and meDNA associated with haplotype, but subsequent analysis showed that meDNA did not mediate the relation between haplotype and CI.

Conclusions

Our findings suggest that CYP17A associates with PFC-dependent cognitive deficits in schizophrenia but did not support the hypothesis that CA plays a role in this association via meDNA or any other mechanism. Grant support: 21-15-00124/Russian Science Foundation https://rscf.ru/project/21-15-00124/.

Disclosure

No significant relationships.

Keywords

schizophréniaDNA methylationCYP17A genechildhood adversity
Type
Abstract
Information
European Psychiatry , Volume 65 , Special Issue S1: Abstracts of the 30th European Congress of Psychiatry , June 2022 , pp. S197
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2022. Published by Cambridge University Press on behalf of the European Psychiatric Association
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