Howard Steiger, PhD*; Linda Booij, PhD*; Esther Kahan, BSc; Kevin McGregor, MSc; Lea Thaler, PhD; Emilie Fletcher, BA; Aurelie Labbe, PhD; Ridha Joober, MD, PhD; Mimi Israël, MD; Moshe Szyf, PhD; Luis B. Agellon, PhD; Lise Gauvin, PhD; Annie St-Hilaire, PhD; Erika Rossi, MA
Background: This study explored state-related tendencies in DNA methylation in people with anorexia nervosa.
Methods: We measured genome-wide DNA methylation in 75 women with active anorexia nervosa (active), 31 women showing stable remission of anorexia nervosa (remitted) and 41 women with no eating disorder (NED). We also obtained postintervention methylation data from 52 of the women from the active group.
Results: Comparisons between members of the active and NED groups showed 58 differentially methylated sites (Q < 0.01) that corresponded to genes relevant to metabolic and nutritional status (lipid and glucose metabolism), psychiatric status (serotonin receptor activity) and immune function. Methylation levels in members of the remitted group differed from those in the active group on 265 probes that also involved sites associated with genes for serotonin and insulin activity, glucose metabolism and immunity. Intriguingly, the direction of methylation effects in remitted participants tended to be opposite to those seen in active participants. The chronicity of Illness correlated (usually inversely, at Q < 0.01) with methylation levels at 64 sites that mapped onto genes regulating glutamate and serotonin activity, insulin function and epigenetic age. In contrast, body mass index increases coincided (at Q < 0.05) with generally increased methylation-level changes at 73 probes associated with lipid and glucose metabolism, immune and inflammatory processes, and olfaction.
Limitations: Sample sizes were modest for this type of inquiry, and findings may have been subject to uncontrolled effects of medication and substance use.
Conclusion: Findings point to the possibility of reversible epigenetic alterations in anorexia nervosa, and suggest that an adequate pathophysiological model would likely need to include psychiatric, metabolic and immune components.
*These authors contributed equally to the work.
Submitted Dec. 12, 2017; Revised May 30, 2018; Revised Aug. 17, 2018; Accepted Sept. 4, 2018; Published online Jan. 29, 2019
Acknowledgements: The study was supported by a grant from the Canadian Institutes of Health Research (CIHR; MOP-142717) awarded to H. Steiger, L. Booij, L. Thaler, A. Labbe, R. Joober, M. Israël, M. Szyf, L. Agellon, L. Gauvin and A. St-Hilaire, and by a donation from Cogir Immobilier. L. Booij was supported by a CIHR New Investigator Award.
Affiliations: From the Eating Disorders Program, Douglas University Institute (Steiger, Kahan, Thaler, Fletcher, Israël, St-Hilaire, Rossi); the Research Centre, Douglas University Institute (Steiger, Kahan, Thaler, Fletcher, Joober, Israël, St-Hilaire, Rossi); the Department of Psychiatry, McGill University (Steiger, Booij, Thaler, Joober, Israël, St-Hilaire); the Department of Psychology, Concordia University (Booij); the Sainte-Justine Hospital Research Centre, University of Montreal (Booij); the Department of Epidemiology, Biostatistics, and Occupational Health, McGill University (McGregor); the Department of Decision Sciences, HEC Montreal (Labbe); the Department of Pharmacology and Therapeutics, McGill University (Szyf); the School of Human Nutrition, McGill University (Agellon); and the Centre de recherche du Centre Hospitalier, de l’Université de Montréal (CRCHUM) (Gauvin), Montreal, Que., Canada.
Competing interests: A. Labbe and R. Joober are members of the journal editorial board; they were not involved in the evaluation or acceptence of this manuscript for publication. R. Joober reports clinician-scientist salary awards from Fonds de recherche du Quebec outside the scope of this work. He participates on the advisory boards and speakers bureaus of Pfizer, Janssen Ortho, Otsuka, Lundbeck, Purdue and Myelin and has received honoraria from those companies. He also reports honoraria from Shire and royalties from Henry Stewart Talks. No other authors have declared competing interests.
Contributors: H. Steiger, L. Booij and M. Israël designed the study. H. Steiger, E. Kahan, L. Thaler, E. Fletcher, M. Israël, A. St-Hilaire and E. Rossi acquired the data, which H. Steiger, L. Booij, K. McGregor, A. Labbe, R. Joober, M. Szyf, L. Agellon and L. Gauvin analyzed. H. Steiger and L. Booij 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: H. Steiger, Eating Disorders Program, Douglas Institute, 6603-05 Lasalle Blvd, Verdun, QC H4H 1R3; email@example.com; L. Booij, Department of Psychology, Concordia University, 7141 Sherbrooke St. W, Montreal, QC H4B 1R6; firstname.lastname@example.org