Ilka Boehm1, Esther Walton1, Nina Alexander1, Victoria-Luise Batury1, Maria Seidel1, Daniel Geisler1, Joseph A. King1, Kerstin Weidner1, Veit Roessner1, Stefan Ehrlich1. 1. From the Division of Psychological and Social Medicine and Developmental Neurosciences, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany (Boehm, Walton, Batury, Seidel, Geisler, King, Ehrlich); the Department of Psychology, University of Bath, Bath, UK (Walton); the Department of Psychology, Faculty of Human Sciences, Medical School Hamburg, Hamburg, Germany (Alexander); the Department of Psychotherapy and Psychosomatic Medicine, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany (Weidner); the Department of Child and Adolescent Psychiatry, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany (Roessner); and the Eating Disorders Research and Treatment Center at the Department of Child and Adolescent Psychiatry, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany (Ehrlich).
Abstract
Background: Epigenetic variation in the serotonin transporter gene (SLC6A4) has been shown to modulate the functioning of brain circuitry associated with the salience network and may heighten the risk for mental illness. This study is, to our knowledge, the first to test this epigenome–brain–behaviour pathway in patients with anorexia nervosa. Methods: We obtained resting-state functional connectivity (rsFC) data and blood samples from 55 acutely underweight female patients with anorexia nervosa and 55 age-matched female healthy controls. We decomposed imaging data using independent component analysis. We used bisulfite pyrosequencing to analyze blood DNA methylation within the promoter region of SLC6A4. We then explored salience network rsFC patterns in the group × methylation interaction. Results: We identified a positive relationship between SLC6A4 methylation levels and rsFC between the dorsolateral prefrontal cortex and the salience network in patients with anorexia nervosa compared to healthy controls. Increased rsFC in the salience network mediated the link between SLC6A4 methylation and eating disorder symptoms in patients with anorexia nervosa. We confirmed findings of rsFC alterations for CpG-specific methylation at a locus with evidence of methylation correspondence between brain and blood tissue. Limitations: This study was cross-sectional in nature, the sample size was modest for the method and methylation levels were measured peripherally, so findings cannot be fully generalized to brain tissue. Conclusion: This study sheds light on the neurobiological process of how epigenetic variation in the SLC6A4 gene may relate to rsFC in the salience network that is linked to psychopathology in anorexia nervosa.
Background: Epigenetic variation in the serotonin transporter gene (SLC6A4) has been shown to modulate the functioning of brain circuitry associated with the salience network and may heighten the risk for mental illness. This study is, to our knowledge, the first to test this epigenome–brain–behaviour pathway in patients with anorexia nervosa. Methods: We obtained resting-state functional connectivity (rsFC) data and blood samples from 55 acutely underweight female patients with anorexia nervosa and 55 age-matched female healthy controls. We decomposed imaging data using independent component analysis. We used bisulfite pyrosequencing to analyze blood DNA methylation within the promoter region of SLC6A4. We then explored salience network rsFC patterns in the group × methylation interaction. Results: We identified a positive relationship between SLC6A4 methylation levels and rsFC between the dorsolateral prefrontal cortex and the salience network in patients with anorexia nervosa compared to healthy controls. Increased rsFC in the salience network mediated the link between SLC6A4 methylation and eating disorder symptoms in patients with anorexia nervosa. We confirmed findings of rsFC alterations for CpG-specific methylation at a locus with evidence of methylation correspondence between brain and blood tissue. Limitations: This study was cross-sectional in nature, the sample size was modest for the method and methylation levels were measured peripherally, so findings cannot be fully generalized to brain tissue. Conclusion: This study sheds light on the neurobiological process of how epigenetic variation in the SLC6A4 gene may relate to rsFC in the salience network that is linked to psychopathology in anorexia nervosa.
Authors: Robert Philibert; Anup Madan; Allan Andersen; Remi Cadoret; Hans Packer; Harinder Sandhu Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2007-01-05 Impact factor: 3.568
Authors: Ilka Boehm; Daniel Geisler; Friederike Tam; Joseph A King; Franziska Ritschel; Maria Seidel; Fabio Bernardoni; Julia Murr; Thomas Goschke; Vince D Calhoun; Veit Roessner; Stefan Ehrlich Journal: J Psychiatry Neurosci Date: 2016-10 Impact factor: 6.186
Authors: S Roberts; K J Lester; J L Hudson; R M Rapee; C Creswell; P J Cooper; K J Thirlwall; J R I Coleman; G Breen; C C Y Wong; T C Eley Journal: Transl Psychiatry Date: 2014-09-16 Impact factor: 6.222
Authors: Ilka Boehm; Julius Hennig; Franziska Ritschel; Daniel Geisler; Joseph A King; Isabel Lesch; Veit Roessner; Florian Daniel Zepf; Stefan Ehrlich Journal: J Psychiatry Neurosci Date: 2022-10-04 Impact factor: 5.699