Ilka Boehm, PhD*; Esther Walton, PhD*; Nina Alexander, PhD; Victoria-Luise Batury, MSc; Maria Seidel, PhD; Daniel Geisler, MSc; Joseph A. King, PhD; Kerstin Weidner, MD; Veit Roessner, MD; Stefan Ehrlich, MD, PhD
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.
*These authors contributed equally to this work.
Submitted Jan. 25, 2019; Revised June 15, 2019; Accepted Aug. 2, 2019; Published online Dec. 5, 2019
Acknowledgments: This work was supported by the Deutsche Forschungsgemeinschaft (DFG EH 367/5-1, EH 367/7-1 & SFB 940) and the Technische Universität Dresden. The authors thank the Center for Information Services and High Performance Computing (ZIH) at Technische Universität Dresden for generous allocations of computer time.
Affiliations: 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).
Competing interests: V. Roessner reports lecture fees from Eli Lilly, Janssen-Cilag, Medice and Novartis and was a member of advisory boards for Eli Lilly and Novartis in the past 2 years. No other authors reported competing interests.
Contributors: E. Walton, D. Geisler, V. Roessner and S. Ehrlich designed the study. I. Boehm, M. Seidel, J. King and K. Weidener acquired the data, which I. Boehm, E. Walton, N. Alexander, V.-L. Batury and S. Ehrlich analyzed. I. Boehm, J. King and S. Ehrlich wrote the article, which all authors reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.
Correspondence to: S. Ehrlich, Division of Psychological and Social Medicine and Developmental Neurosciences, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Translational Developmental Neuroscience Section, Fetscherstrasse 74, 01307 Dresden, Germany; email@example.com