Monica Aas, United Kingdom

King's College London Psychosis Studies

Author Of 1 Presentation

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Oral Communication 17:16 - 17:24

Exploring epigenetic mechanisms linking childhood adversity and psychosis in patients with First Episode of Psychosis – data from the EUGEI study. - O0123

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Abstract

Introduction

Epigenetics is emerging as an important player underlying the interactions between genetic and environmental risk factors in the aetiology of psychiatric disorders. We could hypothesize that epigenetic changes related to childhood adversity (CA) contribute to the underlying mechanism linking CA and psychosis.

Objectives

We aim to explore, whether CA leads to DNA-methylation changes at the level of EWAS in First Episode of Psychosis (FEP) patients. We will also examine whether these changes in DNA-methylation mediate the link between CA and psychosis.

Methods

We used EWAS profiling using the Illumina Infinium Methylation EPIC array in human peripheral blood tissue from 413 FEP and 521 healthy population controls part of the EUGEI study. Polyvictimisation scores were created with the Childhood Trauma Questionnaire (CTQ) ranging from 0-5. Linear regression models at an EWAS level and subsequent mediation analyses were perfomed, adjusting by a broad range of confounding factors.

Results

Preliminary results showed that polyvictimisation scores were significantly associated to the case control status; in cases, EWAS analyses showed that polyvictimization was significantly associated (p<5x10-5) with DNA methylation in 82 probes, located in 48 genes, some of these involved in pathways such as extracellular matrix, neural development or the kynurenine pathway, among other important processes. In controls, DNA methylation changes in such probes did not appear to be associated with polyvictimisation.

Conclusions

Our results show that in FEP, polyvictimisation leads to epigenetic modifications in the form of DNA-methylation in genes previously described in psychosis aetiopathogenesis. Mediation analyses will allow to determine whether changes in these probes mediate the link between adversity and psychosis.

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