Peripheral serotonin transporter DNA methylation is linked to increased salience network connectivity in females with anorexia nervosa

Autor:	Boehm I; 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)., Walton E; 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)., Alexander N; 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)., Batury VL; 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)., Seidel M; 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)., Geisler D; 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)., King JA; 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)., Weidner K; 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)., Roessner V; 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)., Ehrlich S; 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).
Jazyk:	angličtina
Zdroj:	Journal of psychiatry & neuroscience : JPN [J Psychiatry Neurosci] 2020 May 01; Vol. 45 (3), pp. 206-213.
DOI:	10.1503/jpn.190016
Abstrakt:	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. 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. (© 2020 Joule Inc. or its licensors)
Databáze:	MEDLINE
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