This article is available to members only. Please enjoy the abstract for free. Subscribe for instant access to the full article.
This content is restricted to subscribers
Continue Reading...
Did you know members enjoy unlimited free PDF downloads as part of their subscription? Subscribe today for instant access to this article and our entire library in your preferred format. Alternatively, you can purchase the PDF of this article individually.
Members enjoy free PDF downloads on all articles. Join today
Author Affiliations
Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts
Division of Pediatric Endocrinology, Mass General for Children, Massachusetts General Hospital, Boston, Massachusetts
Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts
Eating Disorders Clinical and Research Program, Massachusetts General Hospital, Boston, Massachusetts
Eating Disorders Clinical and Research Program, Massachusetts General Hospital, Boston, Massachusetts
Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
Division of Women’s Health, Department of Medicine and Department of Psychiatry, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
Eating Disorders Clinical and Research Program, Massachusetts General Hospital, Boston, Massachusetts
Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
Great Ormond Street Institute of Child Health, University College London, London, United Kingdom
Department of Pediatrics Gynecology and Obstetrics, Faculty of Medicine, University of Geneva, Geneva, Switzerland
Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts
Division of Pediatric Endocrinology, Mass General for Children, Massachusetts General Hospital, Boston, Massachusetts
Department of Pediatrics, Harvard Medical School, Boston, Massachusetts
Department of Medicine, Harvard Medical School, Boston, Massachusetts
Indicates shared senior authorship.
Eating Disorders Clinical and Research Program, Massachusetts General Hospital, Boston, Massachusetts
Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
Indicates shared senior authorship.
Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts
Department of Medicine, Harvard Medical School, Boston, Massachusetts
Corresponding author: Elizabeth A. Lawson, MD, MMSc, Neuroendocrine Unit, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114 ([email protected]).
Indicates shared senior authorship.
References (75)
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fifth Edition. American Psychiatric Association; 2013.
Fisher MM, Rosen DS, Ornstein RM, et al. Characteristics of avoidant/restrictive food intake disorder in children and adolescents: a “new disorder” in DSM-5. J Adolesc Health. 2014;55(1):49–52. PubMedCrossRef
Cooney M, Lieberman M, Guimond T, et al. Clinical and psychological features of children and adolescents diagnosed with avoidant/restrictive food intake disorder in a pediatric tertiary care eating disorder program: a descriptive study. J Eat Disord. 2018;6(1):7. PubMedCrossRef
Nakai Y, Nin K, Noma S, et al. Clinical presentation and outcome of avoidant/restrictive food intake disorder in a Japanese sample. Eat Behav. 2017;24:49–53. PubMedCrossRef
Strandjord SE, Sieke EH, Richmond M, et al. Avoidant/restrictive food intake disorder: illness and hospital course in patients hospitalized for nutritional insufficiency. J Adolesc Health. 2015;57(6):673–678. PubMedCrossRef
Aulinas A, Marengi DA, Galbiati F, et al. Medical comorbidities and endocrine dysfunction in low-weight females with avoidant/restrictive food intake disorder compared to anorexia nervosa and healthy controls. Int J Eat Disord. 2020;53(4):631–636. PubMedCrossRef
Nicely TA, Lane-Loney S, Masciulli E, et al. Prevalence and characteristics of avoidant/restrictive food intake disorder in a cohort of young patients in day treatment for eating disorders. J Eat Disord. 2014;2(1):21. PubMedCrossRef
Kambanis PE, Kuhnle MC, Wons OB, et al. Prevalence and correlates of psychiatric comorbidities in children and adolescents with full and subthreshold avoidant/restrictive food intake disorder. Int J Eat Disord. 2020;53(2):256–265. PubMedCrossRef
Norris ML, Robinson A, Obeid N, et al. Exploring avoidant/restrictive food intake disorder in eating disordered patients: a descriptive study. Int J Eat Disord. 2014;47(5):495–499. PubMedCrossRef
Brand-Gothelf A, Leor S, Apter A, et al. The impact of comorbid depressive and anxiety disorders on severity of anorexia nervosa in adolescent girls. J Nerv Ment Dis. 2014;202(10):759–762. PubMedCrossRef
Hughes EK, Goldschmidt AB, Labuschagne Z, et al. Eating disorders with and without comorbid depression and anxiety: similarities and differences in a clinical sample of children and adolescents. Eur Eat Disord Rev. 2013;21(5):386–394. PubMedCrossRef
Sander J, Moessner M, Bauer S. Depression, anxiety and eating disorder-related impairment: moderators in female adolescents and young adults. Int J Environ Res Public Health. 2021;18(5):2779. PubMedCrossRef
Kormos V, Gaszner B. Role of neuropeptides in anxiety, stress, and depression: from animals to humans. Neuropeptides. 2013;47(6):401–419. PubMedCrossRef
Wehry AM, Beesdo-Baum K, Hennelly MM, et al. Assessment and treatment of anxiety disorders in children and adolescents. Curr Psychiatry Rep. 2015;17(7):52. PubMedCrossRef
Dalle Grave R, Conti M, Calugi S. Effectiveness of intensive cognitive behavioral therapy in adolescents and adults with anorexia nervosa. Int J Eat Disord. 2020;53(9):1428–1438. PubMedCrossRef
Hay PJ, Claudino AM, Touyz S, et al. Individual psychological therapy in the outpatient treatment of adults with anorexia nervosa. Cochrane Database Syst Rev. 2015;2015(7):CD003909. PubMedCrossRef
Zeeck A, Herpertz-Dahlmann B, Friederich HC, et al. Psychotherapeutic treatment for anorexia nervosa: a systematic review and network meta-analysis. Front Psychiatry. 2018;9:158. PubMedCrossRef
Thomas JJ, Wons OB, Eddy KT. Cognitive-behavioral treatment of avoidant/restrictive food intake disorder. Curr Opin Psychiatry. 2018;31(6):425–430. PubMedCrossRef
Tschöp M, Weyer C, Tataranni PA, et al. Circulating ghrelin levels are decreased in human obesity. Diabetes. 2001;50(4):707–709. PubMedCrossRef
Stone LA, Harmatz ES, Goosens KA. Ghrelin as a stress hormone: implications for psychiatric illness. Biol Psychiatry. 2020;88(7):531–540. PubMedCrossRef
Spencer SJ, Xu L, Clarke MA, et al. Ghrelin regulates the hypothalamic-pituitary-adrenal axis and restricts anxiety after acute stress. Biol Psychiatry. 2012;72(6):457–465. PubMedCrossRef
Alvarez-Crespo M, Skibicka KP, Farkas I, et al. The amygdala as a neurobiological target for ghrelin in rats: neuroanatomical, electrophysiological and behavioral evidence. PLoS One. 2012;7(10):e46321. PubMedCrossRef
Kristenssson E, Sundqvist M, Astin M, et al. Acute psychological stress raises plasma ghrelin in the rat. Regul Pept. 2006;134(2-3):114–117. PubMedCrossRef
Huang CC, Chou D, Yeh CM, et al. Acute food deprivation enhances fear extinction but inhibits long-term depression in the lateral amygdala via ghrelin signaling. Neuropharmacology. 2016;101:36–45. PubMedCrossRef
Asakawa A, Inui A, Kaga T, et al. A role of ghrelin in neuroendocrine and behavioral responses to stress in mice. Neuroendocrinology. 2001;74(3):143–147. PubMedCrossRef
Schmidt MV, Levine S, Alam S, et al. Metabolic signals modulate hypothalamic-pituitary-adrenal axis activation during maternal separation of the neonatal mouse. J Neuroendocrinol. 2006;18(11):865–874. PubMedCrossRef
Meyer RM, Burgos-Robles A, Liu E, et al. A ghrelin-growth hormone axis drives stress-induced vulnerability to enhanced fear. Mol Psychiatry. 2014;19(12):1284–1294. PubMedCrossRef
Yousufzai MIUA, Harmatz ES, Shah M, et al. Ghrelin is a persistent biomarker for chronic stress exposure in adolescent rats and humans. Transl Psychiatry. 2018;8(1):74. PubMedCrossRef
Han QQ, Huang HJ, Wang YL, et al. Ghrelin exhibited antidepressant and anxiolytic effect via the p38-MAPK signaling pathway in hippocampus. Prog Neuropsychopharmacol Biol Psychiatry. 2019;93:11–20. PubMedCrossRef
Lutter M, Sakata I, Osborne-Lawrence S, et al. The orexigenic hormone ghrelin defends against depressive symptoms of chronic stress. Nat Neurosci. 2008;11(7):752–753. PubMedCrossRef
Huang HJ, Zhu XC, Han QQ, et al. Ghrelin alleviates anxiety- and depression-like behaviors induced by chronic unpredictable mild stress in rodents. Behav Brain Res. 2017;326:33–43. PubMedCrossRef
Chuang JC, Perello M, Sakata I, et al. Ghrelin mediates stress-induced food-reward behavior in mice. J Clin Invest. 2011;121(7):2684–2692. PubMedCrossRef
Rouach V, Bloch M, Rosenberg N, et al. The acute ghrelin response to a psychological stress challenge does not predict the post-stress urge to eat. Psychoneuroendocrinology. 2007;32(6):693–702. PubMedCrossRef
Raspopow K, Abizaid A, Matheson K, et al. Psychosocial stressor effects on cortisol and ghrelin in emotional and non-emotional eaters: influence of anger and shame. Horm Behav. 2010;58(4):677–684. PubMedCrossRef
Raspopow K, Abizaid A, Matheson K, et al. Anticipation of a psychosocial stressor differentially influences ghrelin, cortisol and food intake among emotional and non-emotional eaters. Appetite. 2014;74:35–43. PubMedCrossRef
McKay NJ, Giorgianni NR, Czajka KE, et al. Plasma levels of ghrelin and GLP-1, but not leptin or amylin, respond to a psychosocial stressor in women and men. Horm Behav. 2021;134:105017. PubMedCrossRef
Stark R, Santos VV, Geenen B, et al. Des-acyl ghrelin and ghrelin o-acyltransferase regulate hypothalamic-pituitary-adrenal axis activation and anxiety in response to acute stress. Endocrinology. 2016;157(10):3946–3957. PubMedCrossRef
Zhang F, Xu F, Mi X, et al. Ghrelin/GHS-R1a signaling plays different roles in anxiety-related behaviors after acute and chronic caloric restriction. Biochem Biophys Res Commun. 2020;529(4):1131–1136. PubMedCrossRef
Jensen M, Ratner C, Rudenko O, et al. Anxiolytic-like effects of increased ghrelin receptor signaling in the amygdala. Int J Neuropsychopharmacol. 2016;19(5):pyv123. PubMedCrossRef
Kanehisa M, Akiyoshi J, Kitaichi T, et al. Administration of antisense DNA for ghrelin causes an antidepressant and anxiolytic response in rats. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30(8):1403–1407. PubMedCrossRef
Hansson C, Haage D, Taube M, et al. Central administration of ghrelin alters emotional responses in rats: behavioural, electrophysiological and molecular evidence. Neuroscience. 2011;180:201–211. PubMedCrossRef
Carlini VP, Monzón ME, Varas MM, et al. Ghrelin increases anxiety-like behavior and memory retention in rats. Biochem Biophys Res Commun. 2002;299(5):739–743. PubMedCrossRef
Currie PJ, Khelemsky R, Rigsbee EM, et al. Ghrelin is an orexigenic peptide and elicits anxiety-like behaviors following administration into discrete regions of the hypothalamus. Behav Brain Res. 2012;226(1):96–105. PubMedCrossRef
Germain N, Galusca B, Le Roux CW, et al. Constitutional thinness and lean anorexia nervosa display opposite concentrations of peptide YY, glucagon-like peptide 1, ghrelin, and leptin. Am J Clin Nutr. 2007;85(4):967–971. PubMedCrossRef
Misra M, Miller KK, Kuo K, et al. Secretory dynamics of ghrelin in adolescent girls with anorexia nervosa and healthy adolescents. Am J Physiol Endocrinol Metab. 2005;289(2):E347–E356. PubMedCrossRef
Singhal V, Misra M, Klibanski A. Endocrinology of anorexia nervosa in young people: recent insights. Curr Opin Endocrinol Diabetes Obes. 2014;21(1):64–70. PubMedCrossRef
Holsen LM, Lawson EA, Christensen K, et al. Abnormal relationships between the neural response to high- and low-calorie foods and endogenous acylated ghrelin in women with active and weight-recovered anorexia nervosa. Psychiatry Res. 2014;223(2):94–103. PubMedCrossRef
Becker KR, Mancuso C, Dreier MJ, et al. Ghrelin and PYY in low-weight females with avoidant/restrictive food intake disorder compared to anorexia nervosa and healthy controls. Psychoneuroendocrinology. 2021;129:105243. PubMedCrossRef
Ishitobi Y, Kohno K, Kanehisa M, et al. Serum ghrelin levels and the effects of antidepressants in major depressive disorder and panic disorder. Neuropsychobiology. 2012;66(3):185–192. PubMedCrossRef
Hansson C, Annerbrink K, Nilsson S, et al. A possible association between panic disorder and a polymorphism in the preproghrelingene. Psychiatry Res. 2013;206(1):22–25. PubMedCrossRef
Nakashima K, Akiyoshi J, Hatano K, et al. Ghrelin gene polymorphism is associated with depression, but not panic disorder. Psychiatr Genet. 2008;18(5):257. PubMedCrossRef
Lawson EA, Miller KK, Blum JI, et al. Leptin levels are associated with decreased depressive symptoms in women across the weight spectrum, independent of body fat. Clin Endocrinol (Oxf). 2012;76(4):520–525. PubMedCrossRef
Wittekind DA, Kratzsch J, Mergl R, et al. Serum ghrelin is positively associated with physiological anxiety but negatively associated with pathological anxiety in humans: data from a large community-based study. Psychoneuroendocrinology. 2022;140:105728. PubMedCrossRef
Sysko R, Glasofer DR, Hildebrandt T, et al. The eating disorder assessment for DSM-5 (EDA-5): Development and validation of a structured interview for feeding and eating disorders. Int J Eat Disord. 2015;48(5):452–463. PubMedCrossRef
Kaufman J, Birmaher B, Brent D, et al. Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry. 1997;36(7):980–988. PubMedCrossRef
Bryant-Waugh R, Micali N, Cooke L, et al. Development of the Pica, ARFID, and Rumination Disorder Interview, a multi-informant, semi-structured interview of feeding disorders across the lifespan: a pilot study for ages 10–22. Int J Eat Disord. 2019;52(4):378–387. PubMedCrossRef
Harshman SG, Jo J, Kuhnle M, et al. A moving target: how we define avoidant/restrictive food intake disorder can double its prevalence. J Clin Psychiatry. 2021;82(5):20m13831. PubMedCrossRef
Fairburn CG, Beglin SJ. Assessment of eating disorders: interview or self-report questionnaire? Int J Eat Disord. 1994;16(4):363–370. PubMedCrossRef
Spielberger CD. Preliminary Manual for the State-Trait Personality Inventory. Tampa, FL: Human Resources Institute, University South Florida; published online 1996.
Spielberger CD, Edwards CD, Lushene RE, et al Preliminary Test Manual for the State-Trait Anxiety Inventory for Children. Palo Alto, CA: Consulting Psychologists Press; published online 1973.
Rytwinski NK, Fresco DM, Heimberg RG, et al. Screening for social anxiety disorder with the self-report version of the Liebowitz Social Anxiety Scale. Depress Anxiety. 2009;26(1):34–38. PubMedCrossRef
Thomas JJ, Lawson EA, Micali N, et al. Avoidant/restrictive food intake disorder: a three-dimensional model of neurobiology with implications for etiology and treatment. Curr Psychiatry Rep. 2017;19(8):54. PubMedCrossRef
Ghersi MS, Casas SM, Escudero C, et al. Ghrelin inhibited serotonin release from hippocampal slices. Peptides. 2011;32(11):2367–2371. PubMedCrossRef
Brunetti L, Recinella L, Orlando G, et al. Effects of ghrelin and amylin on dopamine, norepinephrine and serotonin release in the hypothalamus. Eur J Pharmacol. 2002;454(2-3):189–192. PubMedCrossRef
Daviu N, Füzesi T, Rosenegger DG, et al. Paraventricular nucleus CRH neurons encode stress controllability and regulate defensive behavior selection. Nat Neurosci. 2020;23(3):398–410. PubMedCrossRef
Labarthe A, Fiquet O, Hassouna R, et al. Ghrelin-derived peptides: a link between appetite/reward, GH axis, and psychiatric disorders? Front Endocrinol (Lausanne). 2014;5:163. PubMedCrossRef
Howick K, Griffin BT, Cryan JF, et al. From belly to brain: targeting the ghrelin receptor in appetite and food intake regulation. Int J Mol Sci. 2017;18(2):273. PubMedCrossRef
De Vriese C, Gregoire F, Lema-Kisoka R, et al. Ghrelin degradation by serum and tissue homogenates: identification of the cleavage sites. Endocrinology. 2004;145(11):4997–5005. PubMedCrossRef
Lee FS, Heimer H, Giedd JN, et al. Adolescent mental health—opportunity and obligation. Science. 2014;346(6209):547–549. PubMedCrossRef
Kessler RC, Berglund P, Demler O, et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):593–602. PubMedCrossRef