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Longitudinal Study of Methylome Profiles in Subjects with Psychosis and/or Schizophrenia

Interview with Oussama Kebir at EPA 2016

Oussama Kebir-HD 1080p

Questions:

00:07 - Could you explain the background to your study on epigenetic changes during the psychotic transition?

00:52 - You designed and performed the first longitudinal study about whole-genome DNA methylation changes during the psychotic transition. Could you explain your methods?

01:57 - What were the results?

03:19 - What are the next steps for your area of research?

03:37 - What could a better physiopathological understanding of psychotic transition mean for clinical practice?

04:10 - What is your take home message?

Congress Abstract:

Longitudinal study of methylome profiles in subjects with psychosis and/or schizophrenia

European Psychiatry

March 2016, Volume 33, Supplement, Page S30

O. Kebir, B. Chaumette,O. Krebs

Background

Schizophrenia is a complex disorder involving both genetic and environmental factors. Epigenetic is a growing theory to explain these interactions at a molecular level. It is well-known that schizophrenia begins with prodromal symptoms and patients undergoing subthreshold symptoms are named ultra-high risk (UHR) subjects. Therapeutic and prognostic attitude remain challenging for this population. According to the model of the gene-environment interactions, the psychotic transition in adolescence could be related to epigenetic changes during the psychotic transition.

Methods

We designed and performed the first longitudinal study about whole-genome DNA methylation changes. Thirty-nine UHR patients were recruited in specialized center C’JAAD - Centre Hospitalier Ste Anne - Paris (France). During follow-up, 14 of them became psychotic (converters) according to the validated scale CAARMS. Initial and final methylation were investigated by Infinium Human Methylation450 BeadChip for 450,000 CpG after bisulfite conversion.

Results

The psychotic transition was not associated with global methylation changes. Linear models failed to identify CpG and genes significantly associated with psychotic transition after Bonferroni correction. Analyses of the top results provided a cluster, which could classify perfectly converters and non-converters. These genes of interest are over-represented in biological pathways with relevance for psychotic physiopathology. Individual analyses highlighted the biological heterogeneity of the psychotic transition.

Conclusion

Improving physiopathological understanding of psychotic transition is a current challenge to identify biomarkers and to develop targeted preventive interventions available in clinical practice for UHR subjects. The epigenetic processes and in particular DNA methylation could be interesting factors.

Link to original article: http://www.europsy-journal.com/article/S0924-9338%2816%2900859-2/abstract

© 2016 Published by Elsevier Inc.