| Autor: |
Carvalho Silva R; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy., Martini P; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy., Hohoff C; Department of Psychiatry and Psychotherapy, University of Münster, Münster, Germany., Mattevi S; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy., Bortolomasi M; Psychiatric Hospital 'Villa Santa Chiara', Verona, Italy., Menesello V; Genetics Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy., Gennarelli M; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.; Genetics Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy., Baune BT; Department of Psychiatry and Psychotherapy, University of Münster, Münster, Germany.; Department of Psychiatry, Melbourne Medical School, University of Melbourne, Melbourne, Australia.; The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia., Minelli A; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.; Genetics Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy. |
| Abstrakt: |
Background : Stressful events increase the risk for treatment-resistant depression (TRD), and trauma-focused psychotherapy can be useful for TRD patients exposed to early life stress (ELS). Epigenetic processes are known to be related to depression and ELS, but there is no evidence of the effects of trauma-focused psychotherapy on methylation alterations. Objective : We performed the first epigenome-wide association study to investigate methylation changes related to trauma-focused psychotherapies effects in TRD patients. Method : Thirty TRD patients assessed for ELS underwent trauma-focused psychotherapy, of those, 12 received trauma-focused cognitive behavioural therapy, and 18 Eye Movement Desensitization and Reprocessing (EMDR). DNA methylation was profiled with Illumina Infinium EPIC array at T0 (baseline), after 8 weeks (T8, end of psychotherapy) and after 12 weeks (T12 - follow-up). We examined differentially methylated CpG sites and regions, as well as pathways analysis in association with the treatment. Results : Main results obtained have shown 110 differentially methylated regions (DMRs) with a significant adjusted p -value area associated with the effects of trauma-focused psychotherapies in the entire cohort. Several annotated genes are related to inflammatory processes and psychiatric disorders, such as LTA , GFI1 , ARID5B , TNFSF13, and LST1. Gene enrichment analyses revealed statistically significant processes related to tumour necrosis factor (TNF) receptor and TNF signalling pathway. Stratified analyses by type of trauma-focused psychotherapy showed statistically significant adjusted p -value area in 141 DMRs only for the group of patients receiving EMDR, with annotated genes related to inflammation and psychiatric disorders, including LTA, GFI1, and S100A8 . Gene set enrichment analyses in the EMDR group indicated biological processes related to inflammatory response, particularly the TNF signalling pathway. Conclusion : We provide preliminary valuable insights into global DNA methylation changes associated with trauma-focused psychotherapies effects, in particular with EMDR treatment. |
