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

IntroductionStress 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)...

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Published in:European psychiatry 2022-06, Vol.65 (S1), p.S197-S197
Main Authors: Alfimova, M., Kondratyev, N., Golov, A., Gabaeva, M., Plakunova, V., Golimbet, V.
Format: Article
Language:English
Subjects:
Abstract
Adverse childhood experiences
childhood adversity
CYP17A gene
DNA methylation
E-Poster Presentation
Haplotypes
Schizophrenia
schizophrénia
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Summary:IntroductionStress 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.ObjectivesTo explore meDNA within CYP17A and its relations to hippocampus- and PFC-dependent schizophrenia symptoms: depression and deficits of declarative memory and executive functions.MethodsWe 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.ResultsMeDNA 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.ConclusionsOur 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/.DisclosureNo significant relationships.
ISSN:0924-9338
1778-3585
DOI:10.1192/j.eurpsy.2022.517