Associations Between Attention-Deficit/Hyperactivity Disorder and Various Eating Disorders: A Swedish Nationwide Population Study Using Multiple Genetically Informative Approaches.
[en] BACKGROUND: Although attention-deficit/hyperactivity disorder (ADHD) and eating disorders (EDs) frequently co-occur, little is known about the shared etiology. In this study, we comprehensively investigated the genetic association between ADHD and various EDs, including anorexia nervosa (AN) and other EDs such as bulimia nervosa. METHODS: We applied different genetically informative designs to register-based information of a Swedish nationwide population (N = 3,550,118). We first examined the familial coaggregation of clinically diagnosed ADHD and EDs across multiple types of relatives. We then applied quantitative genetic modeling in full-sisters and maternal half-sisters to estimate the genetic correlations between ADHD and EDs. We further tested the associations between ADHD polygenic risk scores and ED symptoms, and between AN polygenic risk scores and ADHD symptoms, in a genotyped population-based sample (N = 13,472). RESULTS: Increased risk of all types of EDs was found in individuals with ADHD (any ED: odds ratio [OR] = 3.97, 95% confidence interval [CI] = 3.81, 4.14; AN: OR = 2.68, 95% CI = 2.15, 2.86; other EDs: OR = 4.66, 95% CI = 4.47, 4.87; bulimia nervosa: OR = 5.01, 95% CI = 4.63, 5.41) and their relatives compared with individuals without ADHD and their relatives. The magnitude of the associations decreased as the degree of relatedness decreased, suggesting shared familial liability between ADHD and EDs. Quantitative genetic models revealed stronger genetic correlation of ADHD with other EDs (.37, 95% CI = .31, .42) than with AN (.14, 95% CI = .05, .22). ADHD polygenic risk scores correlated positively with ED symptom measures overall and with the subscales Drive for Thinness and Body Dissatisfaction despite small effect sizes. CONCLUSIONS: We observed stronger genetic association with ADHD for non-AN EDs than for AN, highlighting specific genetic correlation beyond a general genetic factor across psychiatric disorders.
Disciplines :
Genetics & genetic processes
Author, co-author :
Yao, Shuyang
Kuja-Halkola, Ralf
Martin, Joanna
Lu, Yin ; Université de Liège - ULiège > Département de géographie > Géomorphologie et Géologie du Quaternaire
DOCAMPO MARTINEZ, Elisa ; Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de rhumatologie
Language :
English
Title :
Associations Between Attention-Deficit/Hyperactivity Disorder and Various Eating Disorders: A Swedish Nationwide Population Study Using Multiple Genetically Informative Approaches.
Publication date :
2019
Journal title :
Biological Psychiatry
ISSN :
0006-3223
Publisher :
Elsevier, Netherlands
Volume :
86
Issue :
8
Pages :
577-586
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Whiteford HA, Degenhardt L, Rehm J, Baxter AJ, Ferrari AJ, Erskine HE, et al. (2013): Global burden of disease attributable to mental and substance use disorders: Findings from the Global Burden of Disease Study 2010. Lancet 382:1575-1586.
Hudson JI, Hiripi E, Pope HG Jr, Kessler RC (2007): The prevalence and correlates of eating disorders in the National Comorbidity Survey Replication. Biol Psychiatry 61:348-358.
Westmoreland P, Krantz MJ, Mehler PS (2016): Medical complications of anorexia nervosa and bulimia. Am J Med 129:30-37.
Tarver J, Daley D, Sayal K (2014): Attention-deficit hyperactivity disorder (ADHD): An updated review of the essential facts. Child Care Health Dev 40:762-774.
Dalsgaard S, Ostergaard SD, Leckman JF, Mortensen PB, Pedersen MG (2015): Mortality in children, adolescents, and adults with attention deficit hyperactivity disorder: A nationwide cohort study. Lancet 385:2190-2196.
Arcelus J, Mitchell AJ, Wales J, Nielsen S (2011): Mortality rates in patients with anorexia nervosa and other eating disorders: A meta-analysis of 36 studies. Arch Gen Psychiatry 68:724-731.
Chesney E, Goodwin GM, Fazel S (2014): Risks of all-cause and suicide mortality in mental disorders: A meta-review. World Psychiatry 13:153-160.
Ljung T, Chen Q, Lichtenstein P, Larsson H (2014): Common etiological factors of attention-deficit/hyperactivity disorder and suicidal behavior: A population-based study in Sweden. JAMA Psychiatry 71:958-964.
Yao S, Kuja-Halkola R, Thornton LM, Runfola CD, D'Onofrio BM, Almqvist C, et al. (2016): Familial liability for eating disorders and suicide attempts: Evidence from a population registry in Sweden. JAMA Psychiatry 73:284-291.
Sobanski E, Bruggemann D, Alm B, Kern S, Deschner M, Schubert T, et al. (2007): Psychiatric comorbidity and functional impairment in a clinically referred sample of adults with attention-deficit/hyperactivity disorder (ADHD). Eur Arch Psychiatry Clin Neurosci 257:371-377.
Rastam M, Taljemark J, Tajnia A, Lundstrom S, Gustafsson P, Lichtenstein P, et al. (2013): Eating problems and overlap with ADHD and autism spectrum disorders in a nationwide twin study of 9- and 12-year-old children. ScientificWorldJournal 2013:315429.
Yoshimasu K, Barbaresi WJ, Colligan RC, Voigt RG, Killian JM, Weaver AL, et al. (2012): Childhood ADHD is strongly associated with a broad range of psychiatric disorders during adolescence: A population-based birth cohort study. J Child Psychol Psychiatry 53:1036-1043.
Bleck J, DeBate RD (2013): Exploring the co-morbidity of attention-deficit/hyperactivity disorder with eating disorders and disordered eating behaviors in a nationally representative community-based sample. Eat Behav 14:390-393.
Bleck JR, DeBate RD, Olivardia R (2015): The comorbidity of ADHD and eating disorders in a nationally representative sample. J Behav Health Serv Res 42:437-451.
Svedlund NE, Norring C, Ginsberg Y, von Hausswolff-Juhlin Y (2017): Symptoms of attention deficit hyperactivity disorder (ADHD) among adult eating disorder patients. BMC Psychiatry 17:19.
Yilmaz Z, Javaras KN, Baker JH, Thornton LM, Lichtenstein P, Bulik CM, et al. (2017): Association between childhood to adolescent attention deficit/hyperactivity disorder symptom trajectories and late adolescent disordered eating. J Adolesc Health 61:140-146.
Sonneville KR, Calzo JP, Horton NJ, Field AE, Crosby RD, Solmi F, et al. (2015): Childhood hyperactivity/inattention and eating disturbances predict binge eating in adolescence. Psychol Med 45:2511-2520.
Frampton JE (2016): Lisdexamfetamine: A review in ADHD in adults. CNS Drugs 30:343-354.
McElroy SL, Hudson J, Ferreira-Cornwell MC, Radewonuk J, Whitaker T, Gasior M (2016): Lisdexamfetamine dimesylate for adults with moderate to severe binge eating disorder: Results of two pivotal phase 3 randomized controlled trials. Neuropsychopharmacology 41:1251-1260.
Hudson JI, McElroy SL, Ferreira-Cornwell MC, Radewonuk J, Gasior M (2017): Efficacy of lisdexamfetamine in adults with moderate to severe binge-eating disorder: A randomized clinical trial. JAMA Psychiatry 74:903-910.
Bulik CM, Thornton LM, Root TL, Pisetsky EM, Lichtenstein P, Pedersen NL (2010): Understanding the relation between anorexia nervosa and bulimia nervosa in a Swedish national twin sample. Biol Psychiatry 67:71-77.
Larsson H, Chang Z, D'Onofrio BM, Lichtenstein P (2014): The heritability of clinically diagnosed attention deficit hyperactivity disorder across the lifespan. Psychol Med 44:2223-2229.
Chen Q, Brikell I, Lichtenstein P, Serlachius E, Kuja-Halkola R, Sandin S, et al. (2017): Familial aggregation of attention-deficit/hyperactivity disorder. J Child Psychol Psychiatry 58:231-239.
Strober M, Freeman R, Lampert C, Diamond J, Kaye W (2000): Controlled family study of anorexia nervosa and bulimia nervosa: Evidence of shared liability and transmission of partial syndromes. Am J Psychiatry 157:393-401.
Demontis D, Walters RK, Martin J, Mattheisen M, Als TD, Agerbo E, et al. (2019): Discovery of the first genome-wide significant risk loci for attention-deficit/hyperactivity disorder. Nat Genet 51:63-75.
Duncan L, Yilmaz Z, Gaspar H, Walters R, Goldstein J, Anttila V, et al. (2017): Significant locus and metabolic genetic correlations revealed in genome-wide association study of anorexia nervosa. Am J Psychiatry 174:850-858.
Anttila V, Bulik-Sullivan B, Finucane HK, Walters RK, Bras J, Duncan L, et al. (2018): Analysis of shared heritability in common disorders of the brain. Science 360:eaap8757.
Capusan AJ, Yao S, Kuja-Halkola R, Bulik CM, Thornton LM, Bendtsen P, et al. (2017): Genetic and environmental aspects in the association between attention-deficit hyperactivity disorder symptoms and binge-eating behavior in adults: A twin study. Psychol Med 47:2866-2878.
Brikell I, Larsson H, Lu Y, Pettersson E, Chen Q, Kuja-Halkola R, et al. (2018): The contribution of common genetic risk variants for ADHD to a general factor of childhood psychopathology [published online ahead of print Jun 22]. Molecular Psychiatry.
Taylor MJ, Martin J, Lu Y, Brikell I, Lundstrom S, Larsson H, et al. (2018): Association of genetic risk factors for psychiatric disorders and traits of these disorders in a Swedish population twin sample [published online ahead of print Dec 19]. JAMA Psychiatry.
Anckarsater H, Lundstrom S, Kollberg L, Kerekes N, Palm C, Carlstrom E, et al. (2011): The Child and Adolescent Twin Study in Sweden (CATSS). Twin Res Hum Genet 14:495-508.
Ludvigsson JF, Almqvist C, Bonamy AK, Ljung R, Michaelsson K, Neovius M, et al. (2016): Registers of the Swedish total population and their use in medical research. Eur J Epidemiol 31:125-136.
Ludvigsson JF, Andersson E, Ekbom A, Feychting M, Kim JL, Reuterwall C, et al. (2011): External review and validation of the Swedish National Inpatient Register. BMC Public Health 11:450.
Wettermark B, Hammar N, Fored CM, Leimanis A, Otterblad Olausson P, Bergman U, et al. (2007): The new Swedish Prescribed Drug Register-Opportunities for pharmacoepidemiological research and experience from the first six months. Pharmacoepidemiol Drug Saf 16:726-735.
Javaras KN, Runfola CD, Thornton LM, Agerbo E, Birgegard A, Norring C, et al. (2015): Sex- and age-specific incidence of healthcare-register-recorded eating disorders in the complete Swedish 1979-2001 birth cohort. Int J Eat Disord 48:1070-1081.
Emilsson L, Lindahl B, Koster M, Lambe M, Ludvigsson JF (2015): Review of 103 Swedish healthcare quality registries. J Intern Med 277:94-136.
Birgegard A, Bjorck C, Clinton D (2010): Quality assurance of specialised treatment of eating disorders using large-scale internet-based collection systems: Methods, results and lessons learned from designing the Stepwise database. Eur Eat Disord Rev 18:251-259.
Lindevall O (2009): Pastill—A comprehensive clinical database for child and adolescent psychiatry in Stockholm. Presented at the International Conference of the European Society for Child and Adolescent Psychiatry, August 22–26, Budapest, Hungary.
Larson T, Anckarsater H, Gillberg C, Stahlberg O, Carlstrom E, Kadesjo B, et al. (2010): The Autism-Tics, AD/HD and Other Comorbidities inventory (A-TAC): Further validation of a telephone interview for epidemiological research. BMC Psychiatry 10:1.
Garner D (1991): Eating Disorder Inventory-2 Professional Manual. Odessa, FL: Psychological Assessment Resources.
Clausen L, Rokkedal K, Rosenvinge JH (2009): Validating the Eating Disorder Inventory (EDI-2) in two Danish samples: A comparison between female eating disorder patients and females from the general population. Eur Eat Disord Rev 17:462-467.
Nevonen L, Broberg AG (2001): Validating the Eating Disorder Inventory-2 (EDI-2) in Sweden. Eat Weight Disord 6:59-67.
VanderWeele TJ, Robins JM (2007): Directed acyclic graphs, sufficient causes, and the properties of conditioning on a common effect. Am J Epidemiol 166:1096-1104.
Bulik CM, Sullivan PF, Wade TD, Kendler KS (2000): Twin studies of eating disorders: A review. Int J Eat Disord 27:1-20.
Neale MC, Hunter MD, Pritikin JN, Zahery M, Brick TR, Kirkpatrick RM, et al. (2016): OpenMx 2.0: Extended structural equation and statistical modeling. Psychometrika 81:535-549.
Wray NR, Lee SH, Mehta D, Vinkhuyzen AA, Dudbridge F, Middeldorp CM (2014): Research review: Polygenic methods and their application to psychiatric traits. J Child Psychol Psychiatry 55:1068-1087.
1000 Genomes Project Consortium, Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, et al. (2015): A global reference for human genetic variation. Nature 526:68-74.
Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MAR, Bender D, et al. (2007): PLINK: A toolset for whole-genome association and population-based linkage analysis. Am J Hum Genet 81:559–575.
Ware EB, Schmitz LL, Faul JD, Gard A, Mitchell C, Smith JA, et al. (2017): Heterogeneity in polygenic scores for common human traits [published online ahead of print Feb 5]. bioRxiv.
Zetterqvist J, Sjolander A (2015): Doubly robust estimation with the R package drgee. Epidemiol Methods 4:69-86.
Bland JM, Altman DG (1997): Cronbach's alpha. BMJ 314:572.
Widiger TA, Samuel DB (2005): Diagnostic categories or dimensions? A question for the Diagnostic and Statistical Manual of Mental Disorders-fifth edition. J Abnorm Psychol 114:494-504.
Greenland S (2003): Quantifying biases in causal models: Classical confounding vs collider-stratification bias. Epidemiology 14:300-306.
Chen Q, Kuja-Halkola R, Sjolander A, Serlachius E, Cortese S, Faraone SV, et al. (2017): Shared familial risk factors between attention-deficit/hyperactivity disorder and overweight/obesity-A population-based familial coaggregation study in Sweden. J Child Psychol Psychiatry 58:711-718.
Nigg JT, Johnstone JM, Musser ED, Long HG, Willoughby MT, Shannon J (2016): Attention-deficit/hyperactivity disorder (ADHD) and being overweight/obesity: New data and meta-analysis. Clin Psychol Rev 43:67-79.
Cortese S, Moreira-Maia CR, St Fleur D, Morcillo-Penalver C, Rohde LA, Faraone SV (2016): Association between ADHD and obesity: A systematic review and meta-analysis. Am J Psychiatry 173:34-43.
Patte KA, Davis CA, Levitan RD, Kaplan AS, Carter-Major J, Kennedy JL (2016): A behavioral genetic model of the mechanisms underlying the link between obesity and symptoms of ADHD [published online ahead of print Jan 21]. J Atten Disord.
Vogel SW, Bijlenga D, Tanke M, Bron TI, van der Heijden KB, Swaab H, et al. (2015): Circadian rhythm disruption as a link between attention-deficit/hyperactivity disorder and obesity? J Psychosom Res 79:443-450.
Pettersson E, Anckarsater H, Gillberg C, Lichtenstein P (2013): Different neurodevelopmental symptoms have a common genetic etiology. J Child Psychol Psychiatry 54:1356-1365.
Schag K, Schonleber J, Teufel M, Zipfel S, Giel KE (2013): Food-related impulsivity in obesity and binge eating disorder-A systematic review. Obes Rev 14:477-495.
Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, et al. (2009): Finding the missing heritability of complex diseases. Nature 461:747-753.
Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014): Biological insights from 108 schizophrenia-associated genetic loci. Nature 511:421-427.
American Psychiatric Association (2013): Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Washington, DC: American Psychiatric Press.
