Miriam A Schiele1, Christiane Thiel1, Leonie Kollert2, Lena Fürst3, Lisa Putschin3, Rebekka Kehle3, Walter Hauke3, Marina Mahr2, Elena Reinhold1, Michael G Gottschalk1, Markus Heinrichs4, Michael Zaudig3, Götz Berberich3, Katharina Domschke5,6. 1. Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 2. Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany. 3. Psychosomatic Hospital Windach, Windach, Germany. 4. Laboratory for Biological and Personality Psychology, Department of Psychology, University of Freiburg, Freiburg, Germany. 5. Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany, katharina.domschke@uniklinik-freiburg.de. 6. Center for Basics in NeuroModulation, Faculty of Medicine, University of Freiburg, Freiburg, Germany, katharina.domschke@uniklinik-freiburg.de.
Abstract
INTRODUCTION: Obsessive-compulsive disorder (OCD) is associated with high chronicity and treatment resistance, indicating the need for early therapy response markers enabling fast and personalized treatment adaptations. Although epigenetic mechanisms such as DNA methylation of the oxytocin receptor (OXTR) gene have previously been linked to OCD pathogenesis, epigenetic markers as predictors of treatment success have not yet been investigated in OCD. OBJECTIVE: For the first time, this therapyepigenetic study aimed to investigate the role of OXTR methylation as a treatment response marker in OCD. METHODS: In total, 113 inpatients with OCD (57 females) were compared to 113 age- and sex-matched healthy controls. Patients were investigated over a 10-week course of standardized, OCD-specific cognitive-behavioral psychotherapy. Clinical response was measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) at baseline, before in vivo exposure, and after therapy. OXTR exon III methylation was analyzed via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. RESULTS: Relative OXTR hypermethylation was observed in OCD patients compared to healthy controls. In OCD, higher baseline OXTR methylation was found to predict impaired treatment response at both categorical (responders vs. nonresponders) and dimensional (relative Y-BOCS reduction) levels, whereas lower baseline methylation was related to treatment response and greater symptom improvements. Analysis of Y-BOCS subdimensions revealed that the association between OXTR hypermethylation with impaired treatment response applied especially to symptoms related to obsessions, but not compulsions. CONCLUSIONS: OXTR hypermethylation may constitute a predictive marker of impaired treatment response in OCD and thus carries great potential for future personalized treatment efforts in OCD.
INTRODUCTION: Obsessive-compulsive disorder (OCD) is associated with high chronicity and treatment resistance, indicating the need for early therapy response markers enabling fast and personalized treatment adaptations. Although epigenetic mechanisms such as DNA methylation of the oxytocin receptor (OXTR) gene have previously been linked to OCD pathogenesis, epigenetic markers as predictors of treatment success have not yet been investigated in OCD. OBJECTIVE: For the first time, this therapyepigenetic study aimed to investigate the role of OXTR methylation as a treatment response marker in OCD. METHODS: In total, 113 inpatients with OCD (57 females) were compared to 113 age- and sex-matched healthy controls. Patients were investigated over a 10-week course of standardized, OCD-specific cognitive-behavioral psychotherapy. Clinical response was measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) at baseline, before in vivo exposure, and after therapy. OXTR exon III methylation was analyzed via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. RESULTS: Relative OXTR hypermethylation was observed in OCD patients compared to healthy controls. In OCD, higher baseline OXTR methylation was found to predict impaired treatment response at both categorical (responders vs. nonresponders) and dimensional (relative Y-BOCS reduction) levels, whereas lower baseline methylation was related to treatment response and greater symptom improvements. Analysis of Y-BOCS subdimensions revealed that the association between OXTR hypermethylation with impaired treatment response applied especially to symptoms related to obsessions, but not compulsions. CONCLUSIONS: OXTR hypermethylation may constitute a predictive marker of impaired treatment response in OCD and thus carries great potential for future personalized treatment efforts in OCD.
Authors: Miriam A Schiele; Jan Lipovsek; Pascal Schlosser; Michael Soutschek; Gerhard Schratt; Michael Zaudig; Götz Berberich; Anna Köttgen; Katharina Domschke Journal: Transl Psychiatry Date: 2022-06-01 Impact factor: 7.989
Authors: Katharina Domschke; Ludger Tebartz van Elst; Miriam A Schiele; Dominique Endres; Thomas A Pollak; Karl Bechter; Dominik Denzel; Karoline Pitsch; Kathrin Nickel; Kimon Runge; Benjamin Pankratz; David Klatzmann; Ryad Tamouza; Luc Mallet; Marion Leboyer; Harald Prüss; Ulrich Voderholzer; Janet L Cunningham Journal: Transl Psychiatry Date: 2022-01-10 Impact factor: 6.222
Authors: Natalia Rodriguez; Albert Martinez-Pinteño; Ana Blázquez; Ana Encarnación Ortiz; Elena Moreno; Patricia Gassó; Amalia Lafuente; Luisa Lazaro; Sergi Mas Journal: Pharmgenomics Pers Med Date: 2021-06-29