{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T01:53:41Z","timestamp":1790733221007,"version":"4.1.0"},"reference-count":58,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,30]],"date-time":"2024-06-30T00:00:00Z","timestamp":1719705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Nursing Research","award":["T32 NR007091"],"award-info":[{"award-number":["T32 NR007091"]}]},{"name":"National Institute of Nursing Research","award":["K01 MH106675"],"award-info":[{"award-number":["K01 MH106675"]}]},{"name":"National Institute of Mental Health","award":["T32 NR007091"],"award-info":[{"award-number":["T32 NR007091"]}]},{"name":"National Institute of Mental Health","award":["K01 MH106675"],"award-info":[{"award-number":["K01 MH106675"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>The pathogenesis of anorexia nervosa (AN) has been hypothesized to involve several biological systems. However, reliable biomarkers for AN have yet to be established. This study was aimed to identify statistically significant and clinically meaningful peripheral biomarkers associated with AN. A systematic literature search was conducted to identify studies published in English from inception until 30 June 2022. We conducted two-level random-effects meta-analyses to examine the difference between AN and comparison groups across 52 distinct biomarkers and found that acylated ghrelin, adrenocorticotropic hormone (ACTH), carboxy-terminal collagen crosslinks (CTX), cholesterol, cortisol, des-acyl ghrelin, ghrelin, growth hormone (GH), obestatin, and soluble leptin receptor levels were significantly higher in cases of AN compared with those in non-AN controls. Conversely, C-reactive protein (CRP), CD3 positive, CD8, creatinine, estradiol, follicle-stimulating hormone (FSH), free thyroxine, free triiodothyronine, glucose, insulin, insulin-like growth factor 1 (IGF-1), leptin, luteinizing hormone, lymphocyte, and prolactin levels were significantly lower in AN compared with those in non-AN controls. Our findings indicate that peripheral biomarkers may be linked to the pathophysiology of AN, such as processes of adaptation to starvation. Scientific investigation into peripheral biomarkers may ultimately yield breakthroughs in personalized clinical care for AN.<\/jats:p>","DOI":"10.3390\/nu16132095","type":"journal-article","created":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T04:53:27Z","timestamp":1719809607000},"page":"2095","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Peripheral Biomarkers of Anorexia Nervosa: A Meta-Analysis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8990-3449","authenticated-orcid":false,"given":"Ya-Ke","family":"Wu","sequence":"first","affiliation":[{"name":"School of Nursing, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"},{"name":"Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hunna J.","family":"Watson","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"},{"name":"School of Psychology, Curtin University, Bentley, WA 6102, Australia"},{"name":"School of Paediatrics, Division of Medicine, The University of Western Australia, Crawley, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron C.","family":"Del Re","sequence":"additional","affiliation":[{"name":"Del Re Data & Statistical Consulting, San Diego, CA 91910, USA"},{"name":"Department of Psychology, University of Kassel, 34127 Kassel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jody E.","family":"Finch","sequence":"additional","affiliation":[{"name":"Department of Psychology, Georgia State University, Atlanta, GA 30302, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina L.","family":"Hardin","sequence":"additional","affiliation":[{"name":"National Center for PTSD, VA Boston Healthcare System, Boston, MA 02130, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2092-357X","authenticated-orcid":false,"given":"Alexis S.","family":"Dumain","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly A.","family":"Brownley","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica H.","family":"Baker","sequence":"additional","affiliation":[{"name":"Equip Health, Inc., P.O. Box 131747, Carlsbad, CA 92013, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"APA (2013). Diagnostic and Statistical Manual of Mental Disorders, American Psychiatric Association. [5th ed.].","DOI":"10.1176\/appi.books.9780890425596"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1093\/ajcn\/nqy342","article-title":"Prevalence of eating disorders over the 2000\u20132018 period: A systematic literature review","volume":"109","author":"Galmiche","year":"2019","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1001\/archgenpsychiatry.2011.74","article-title":"Mortality rates in patients with anorexia nervosa and other eating disorders. A meta-analysis of 36 studies","volume":"68","author":"Arcelus","year":"2011","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_4","first-page":"70","article-title":"Anorexia nervosa\/atypical anorexia nervosa","volume":"47","author":"Moskowitz","year":"2017","journal-title":"Curr. Probl. Pediatr. Adolesc. Health Care"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.jpsychires.2021.02.063","article-title":"Current directions in biomarkers and endophenotypes for anorexia nervosa: A scoping review","volume":"137","author":"Malcolm","year":"2021","journal-title":"J. Psychiatr. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0098-2997(02)00017-1","article-title":"Biomarkers","volume":"23","author":"Griffiths","year":"2002","journal-title":"Mol. Asp. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.tips.2016.10.012","article-title":"Towards precision medicine in the clinic: From biomarker discovery to novel therapeutics","volume":"38","author":"Collins","year":"2017","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1097\/COH.0b013e32833ed177","article-title":"What are biomarkers?","volume":"5","author":"Strimbu","year":"2010","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.jpsychires.2018.06.002","article-title":"A meta-analysis of cytokine concentrations in eating disorders","volume":"103","author":"Dalton","year":"2018","journal-title":"J. Psychiatr. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.bbi.2019.05.012","article-title":"A longitudinal analysis of cytokines in anorexia nervosa","volume":"85","author":"Dalton","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/s00702-010-0551-z","article-title":"Screening for anorexia nervosa via measurement of serum leptin levels","volume":"118","author":"Timmesfeld","year":"2011","journal-title":"J. Neural Transm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.psychres.2016.04.117","article-title":"Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis","volume":"241","author":"Rutigliano","year":"2016","journal-title":"Psychiatry Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s11920-018-0957-0","article-title":"The Neuropeptide Hormone Oxytocin in Eating Disorders","volume":"20","author":"Plessow","year":"2018","journal-title":"Curr. Psychiatry Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1016\/j.jpsychires.2012.08.015","article-title":"Comparison of metabolic profiles of acutely ill and short-term weight recovered patients with anorexia nervosa reveals alterations of 33 out of 163 metabolites","volume":"46","author":"Timmesfeld","year":"2012","journal-title":"J. Psychiatr. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3980","DOI":"10.1038\/s41380-019-0573-3","article-title":"Metabolomics signatures of acutely ill and short-term weight recovered women with anorexia nervosa","volume":"26","author":"Monteleone","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"104485","DOI":"10.1016\/j.psyneuen.2019.104485","article-title":"Adipokines in anorexia nervosa: A systematic review and meta-analysis","volume":"112","author":"Karageorgiou","year":"2020","journal-title":"Psychoneuroendocrinology"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Seidel, M., Markmann Jensen, S., Healy, D., Dureja, A., Watson, H.J., Holst, B., Bulik, C.M., and Sj\u00f6gren, J.M. (2021). A systematic review and meta-analysis finds increased blood levels of all forms of ghrelin in both restricting and binge-eating\/purging subtypes of anorexia nervosa. Nutrients, 13.","DOI":"10.3390\/nu13020709"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.ijsu.2010.02.007","article-title":"Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement","volume":"8","author":"Moher","year":"2009","journal-title":"Int. J. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1001\/archpsyc.1972.01750190059011","article-title":"Diagnostic criteria for use in psychiatric research","volume":"26","author":"Feighner","year":"1972","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_20","unstructured":"Microsoft (2024, June 20). Microsoft Excel. Available online: https:\/\/office.microsoft.com\/excel."},{"key":"ref_21","unstructured":"Institute, T.J.B. (2014). Joanna Briggs Institute Reviewers\u2019 Manual: 2014 Edition, Joanna Briggs Institute."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1002\/sim.8781","article-title":"Evaluation of various estimators for standardized mean difference in meta-analysis","volume":"40","author":"Lin","year":"2021","journal-title":"Stat. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v036.i03","article-title":"Conducting meta-analyses in R with the metafor package","volume":"36","author":"Viechtbauer","year":"2010","journal-title":"J. Stat. Softw."},{"key":"ref_24","unstructured":"Del, A.C.R., and Hoyt, W.T. (2023, November 01). MAd: Meta-Analysis with Mean Differences (R Package Version 0.8-2). Available online: https:\/\/CRAN.R-project.org\/package=MAd."},{"key":"ref_25","unstructured":"Hedges, L.V., and Olkin, I. (1985). Statistical Methods for Meta-Analysis, Academic Press."},{"key":"ref_26","unstructured":"Raudenbush, S.W., and Bryk, A.S. (2002). Hierarchical Linear Models: Applications and Data Analysis Methods, Sage."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1177\/1536867X0400400204","article-title":"Funnel plots in meta-analysis","volume":"4","author":"Sterne","year":"2004","journal-title":"Stata J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1002\/jrsm.1095","article-title":"Meta-regression approximations to reduce publication selection bias","volume":"5","author":"Stanley","year":"2014","journal-title":"Res. Synth. Methods"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1177\/1745691616662243","article-title":"Adjusting for publication bias in meta-analysis: An evaluation of selection methods and some cautionary notes","volume":"11","author":"McShane","year":"2016","journal-title":"Perspect. Psychol. Sci."},{"key":"ref_30","unstructured":"Higgins, J.P.T., Thomas, J., Chandler, J., Cumpston, M., Li, T., Page, M.J., and Welch, V.A. (2023). Cochrane Handbook for Systematic Reviews of Interventions Version 6.4, Cochrane."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jpsychires.2005.12.005","article-title":"An investigation of hypothalamic-pituitary-adrenal axis hyperactivity in anorexia nervosa: The role of CRH and AVP","volume":"41","author":"Connan","year":"2007","journal-title":"J. Psychiatr. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1093\/ajcn\/86.1.92","article-title":"Treatment of anorexia nervosa is associated with increases in bone mineral density, and recovery is a biphasic process involving both nutrition and return of menses","volume":"86","author":"Dominguez","year":"2007","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/erv.2303","article-title":"Central and peripheral peptides regulating eating behaviour and energy homeostasis in anorexia nervosa and bulimia nervosa: A literature review","volume":"22","author":"Tortorella","year":"2014","journal-title":"Eur. Eat. Disord. Rev. J. Eat. Disord. Assoc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.physbeh.2009.06.010","article-title":"Estradiol and the control of food intake","volume":"99","author":"Butera","year":"2010","journal-title":"Physiol. Behav."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"817457","DOI":"10.1155\/2010\/817457","article-title":"Interactions of gastrointestinal peptides: Ghrelin and its anorexigenic antagonists","volume":"2010","author":"Wisser","year":"2010","journal-title":"Int. J. Pept."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.nut.2011.01.002","article-title":"Ghrelin reactive autoantibodies in restrictive anorexia nervosa","volume":"27","author":"Terashi","year":"2011","journal-title":"Nutrition"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1210\/jc.2003-031861","article-title":"Growth hormone and ghrelin responses to an oral glucose load in adolescent girls with anorexia nervosa and controls","volume":"89","author":"Misra","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/nrendo.2016.222","article-title":"The cellular and molecular bases of leptin and ghrelin resistance in obesity","volume":"13","author":"Cui","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/S2213-8587(13)70180-3","article-title":"Endocrine consequences of anorexia nervosa","volume":"2","author":"Misra","year":"2014","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"145","DOI":"10.6065\/apem.2017.22.3.145","article-title":"Effects of growth hormone on glucose metabolism and insulin resistance in human","volume":"22","author":"Kim","year":"2017","journal-title":"Ann. Pediatr. Endocrinol. Metab."},{"key":"ref_41","first-page":"101240","article-title":"Menstrual disorders in adolescents and young adults with eating disorders","volume":"52","author":"Saldanha","year":"2022","journal-title":"Curr. Probl. Pediatr. Adolesc. Health Care"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1210\/jc.2009-2304","article-title":"Endocrine manifestations of eating disorders","volume":"96","author":"Warren","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/978-1-4939-0659-8_7","article-title":"The endocrinology of the menstrual cycle","volume":"1154","author":"Barbieri","year":"2014","journal-title":"Methods Mol. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s40261-019-00854-w","article-title":"Targeting hormones for improving cognition in major mood disorders and schizophrenia: Thyroid hormones and prolactin","volume":"40","author":"Tost","year":"2020","journal-title":"Clin. Drug Investig."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"105630","DOI":"10.1016\/j.psyneuen.2021.105630","article-title":"Associations between pituitary-thyroid hormones and depressive symptoms in individuals with anorexia nervosa before and after weight-recovery","volume":"137","author":"Wronski","year":"2022","journal-title":"Psychoneuroendocrinology"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Montalvo, I., Guti\u00e9rrez-Zotes, A., Creus, M., Monseny, R., Ortega, L., Franch, J., Lawrie, S.M., Reynolds, R.M., Vilella, E., and Labad, J. (2014). Increased prolactin levels are associated with impaired processing speed in subjects with early psychosis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0089428"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1042\/cs1010739","article-title":"Cortisol increases gluconeogenesis in humans: Its role in the metabolic syndrome","volume":"101","author":"Khani","year":"2001","journal-title":"Clin. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1038\/s41393-019-0322-0","article-title":"Carboxy terminal collagen crosslinks as a prognostic risk factor for fall-related fractures in individuals with established spinal cord injury","volume":"57","author":"Slettahjell","year":"2019","journal-title":"Spinal Cord."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.bone.2007.03.018","article-title":"Skeletal status and laboratory investigations in adolescent girls with anorexia nervosa","volume":"41","author":"Ziora","year":"2007","journal-title":"Bone"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.psyneuen.2014.09.031","article-title":"Inflammatory cytokines and anorexia nervosa: A meta-analysis of cross-sectional and longitudinal studies","volume":"51","author":"Solmi","year":"2015","journal-title":"Psychoneuroendocrinology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1038\/sj.ijo.0801792","article-title":"The relation of body fat mass and distribution to markers of chronic inflammation","volume":"25","author":"Festa","year":"2001","journal-title":"Int. J. Obes."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.nutres.2017.02.006","article-title":"Increased naive CD4+ and B lymphocyte subsets are associated with body mass loss and drive relative lymphocytosis in anorexia nervosa patients","volume":"39","author":"Elegido","year":"2017","journal-title":"Nutr. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1002\/eat.20417","article-title":"Malnutrition induces dissociated changes in lymphocyte count and subset proportion in patients with anorexia nervosa","volume":"40","author":"Saito","year":"2007","journal-title":"Int. J. Eat. Disord."},{"key":"ref_54","first-page":"294","article-title":"Immune disorders in anorexia","volume":"42","year":"2017","journal-title":"Cent. Eur. J. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1002\/1098-108X(199207)12:1<47::AID-EAT2260120107>3.0.CO;2-D","article-title":"Risk of infection and immune function in anorexia nervosa","volume":"12","author":"Pomeroy","year":"1992","journal-title":"Int. J. Eat. Disord."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"23","DOI":"10.12788\/cp.0011","article-title":"Anorexia nervosa and COVID-19","volume":"19","author":"DeSarbo","year":"2020","journal-title":"Curr. Psychiatry"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.3758\/s13428-020-01360-0","article-title":"Multiple moderator meta-analysis using the R-package Meta-CART","volume":"52","author":"Li","year":"2020","journal-title":"Behav. Res. Methods"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.12968\/hmed.2020.0099","article-title":"Anorexia nervosa in adolescents","volume":"81","author":"Neale","year":"2020","journal-title":"Br. J. Hosp. Med."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/13\/2095\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:08:05Z","timestamp":1760108885000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/13\/2095"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,30]]},"references-count":58,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["nu16132095"],"URL":"https:\/\/doi.org\/10.3390\/nu16132095","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,30]]}}}