{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:23:16Z","timestamp":1760145796884,"version":"build-2065373602"},"reference-count":42,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,9,1]],"date-time":"2024-09-01T00:00:00Z","timestamp":1725148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundaci\u00f3n Alicia Koplowitz"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Objectives: This study aimed to investigate whether genetic variations in the OPRD1 gene affect psychopathological symptoms and personality dimensions in eating disorders (ED) patients and\/or contribute to ED risk. Methods: The study involved 221 female patients with anorexia nervosa (AN), 88 with bulimia nervosa (BN), and 396 controls. Sixteen tag-single nucleotide polymorphisms (SNPs) in OPRD1 were identified. Psychometric evaluations were conducted using the Symptom Checklist 90 Revised (SCL-90R) and the Eating Disorders Inventory Test-2 (EDI-2). p-values obtained by regression models were corrected for multiple testing by the False Discovery Rate (FDR) method. Results: In AN patients, genotypes rs204077TT and rs169450TT were linked to lower body-mass index (BMI) values (FDR-q = 0.035 and 0.017, respectively), as was rs2234918 in a log-additive model (BMI: 18.0 \u00b1 0.28, 17.22 \u00b1 0.18 and 16.59 \u00b1 0.39 for TT, TC and CC carriers, FDR-q = 0.012). Additionally, AN patients carrying the rs72665504AA genotype had higher scores in interpersonal distrust (FDR-q = 0.030), whilst BN carriers of rs513269TT and rs2873795TT showed lower scores in ineffectiveness (FDR-q = 0.041 and FDR-q = 0.021). In the AN group, BMI correlated with variability in a distal haplotype (rs508448\/rs204077\/rs223491, FDR-q = 0.028), which was also associated with the global positive symptom total (PST) index of SCL-90R (FDR-q = 0.048). Associations were more noticeable in BN patients; again, the distal region of the gene was linked to EDI-2 total scores (FDR-q = 0.004\u20130.048 for the four last haplotypes) and two global SCL-90R indices (GSI: FDR-q = 0.011 and positive symptom distress index (PSDI): FDR-q = 0.003 for the last s204077\/rs2234918\/rs169450 combination). No associations with ED risk were observed. Conclusions: Genetic variation in the OPRD1 gene, particularly in its distal region, is associated with BMI and psychopathological comorbidities in ED patients.<\/jats:p>","DOI":"10.3390\/jcm13175189","type":"journal-article","created":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T10:07:35Z","timestamp":1725271655000},"page":"5189","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of OPRD1 Gene Variants with Changes in Body Weight and Psychometric Indicators in Patients with Eating Disorders"],"prefix":"10.3390","volume":"13","author":[{"given":"Laura","family":"Gonz\u00e1lez-Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Department of Medical & Surgical Therapeutics, Medical School, University of Extremadura, 06006 Badajoz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luz Mar\u00eda","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Medical & Surgical Therapeutics, Medical School, University of Extremadura, 06006 Badajoz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angustias","family":"Garc\u00eda-Herr\u00e1iz","sequence":"additional","affiliation":[{"name":"Eating Disorders Unit, Health Service of Extremadura, 06010 Badajoz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4165-9613","authenticated-orcid":false,"given":"Sonia","family":"Mota-Zamorano","sequence":"additional","affiliation":[{"name":"Department of Medical & Surgical Therapeutics, Medical School, University of Extremadura, 06006 Badajoz, Spain"},{"name":"Institute of Molecular Pathology Biomarkers, University of Extremadura, 06010 Badajoz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isalud","family":"Flores","sequence":"additional","affiliation":[{"name":"Eating Disorders Unit, Health Service of Extremadura, 06010 Badajoz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0524-9767","authenticated-orcid":false,"given":"Guillermo","family":"Gervasini","sequence":"additional","affiliation":[{"name":"Department of Medical & Surgical Therapeutics, Medical School, University of Extremadura, 06006 Badajoz, Spain"},{"name":"Institute of Molecular Pathology Biomarkers, University of Extremadura, 06010 Badajoz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hamson, A., Hill, S., Hafeez, A., Clark, M., and Butcher, R. (2023). Early Intervention Programs for Adolescents and Young Adults with Eating Disorders: Main Report, CADTH Health Technology Review.","DOI":"10.51731\/cjht.2023.801"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/s41593-022-01071-z","article-title":"Genetics and neurobiology of eating disorders","volume":"25","author":"Bulik","year":"2022","journal-title":"Nat. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/978-3-031-45493-6_17","article-title":"Role of Endogenous Opioids in the Pathophysiology of Obesity and Eating Disorders","volume":"35","author":"Zuniga","year":"2024","journal-title":"Adv. Neurobiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/978-3-031-45493-6_16","article-title":"Endogenous Opioids in the Homeostatic Regulation of Hunger, Satiety, and Hedonic Eating: Neurobiological Foundations","volume":"35","author":"Flores","year":"2024","journal-title":"Adv. Neurobiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"104711","DOI":"10.1016\/j.psyneuen.2020.104711","article-title":"Decreased cerebral opioid receptors availability related to hormonal and psychometric profile in restrictive-type anorexia nervosa","volume":"118","author":"Galusca","year":"2020","journal-title":"Psychoneuroendocrinology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/978-3-031-45493-6_18","article-title":"Integration of Endogenous Opioid System Research in the Interprofessional Diagnosis and Treatment of Obesity and Eating Disorders","volume":"35","author":"Flores","year":"2024","journal-title":"Adv. Neurobiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1086\/339250","article-title":"Evidence for a susceptibility gene for anorexia nervosa on chromosome 1","volume":"70","author":"Grice","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/sj.mp.4001318","article-title":"Candidate genes for anorexia nervosa in the 1p33\u201336 linkage region: Serotonin 1D and delta opioid receptor loci exhibit significant association to anorexia nervosa","volume":"8","author":"Bergen","year":"2003","journal-title":"Mol. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.biopsych.2006.04.007","article-title":"Further evidence of association of OPRD1 & HTR1D polymorphisms with susceptibility to anorexia nervosa","volume":"61","author":"Brown","year":"2007","journal-title":"Biol. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/mp.2010.107","article-title":"A genome-wide association study on common SNPs and rare CNVs in anorexia nervosa","volume":"16","author":"Wang","year":"2011","journal-title":"Mol. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1038\/mp.2013.187","article-title":"A genome-wide association study of anorexia nervosa","volume":"19","author":"Boraska","year":"2014","journal-title":"Mol. Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"12856","DOI":"10.3892\/mmr.2022.12856","article-title":"Rubiscolin-6 rapidly suppresses the postprandial motility of the gastric antrum and subsequently increases food intake via \u03b4-opioid receptors in mice","volume":"26","author":"Ataka","year":"2022","journal-title":"Mol. Med. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Sudakov, S., and Bogdanova, N. (2020). Involvement of Peripheral Opioid Receptors in the Realization of Food Motivation into Eating Behavior. Front. Behav. Neurosci., 14.","DOI":"10.3389\/fnbeh.2020.600920"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/s41398-023-02585-1","article-title":"Genome-wide analysis of anorexia nervosa and major psychiatric disorders and related traits reveals genetic overlap and identifies novel risk loci for anorexia nervosa","volume":"13","author":"Bang","year":"2023","journal-title":"Transl. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1097\/YCO.0000000000000278","article-title":"Epidemiology of eating disorders in Europe: Prevalence, incidence, comorbidity, course, consequences, and risk factors","volume":"29","author":"Mustelin","year":"2016","journal-title":"Curr. Opin. Psychiatry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.1007\/s40519-021-01106-7","article-title":"Variability in cannabinoid receptor genes is associated with psychiatric comorbidities in anorexia nervosa","volume":"26","author":"Flores","year":"2021","journal-title":"Eat. Weight. Disord."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.gene.2018.02.035","article-title":"Effect of dopamine receptor D4 (DRD4) haplotypes on general psychopathology in patients with eating disorders","volume":"654","author":"Gervasini","year":"2018","journal-title":"Gene"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s40519-019-00820-7","article-title":"Genetic variants in dopamine pathways affect personality dimensions displayed by patients with eating disorders","volume":"26","author":"Gervasini","year":"2021","journal-title":"Eat. Weight. Disord."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1097\/JCP.0b013e3182539f2b","article-title":"Polymorphisms in Serotonergic Genes and Psychopathological Traits in Eating Disorders","volume":"32","author":"Gervasini","year":"2012","journal-title":"J. Clin. Psychopharmacol."},{"key":"ref_20","unstructured":"Derogaitis, L.R. (2002). SCL-90R: Cuestionario de 90 S\u00edntomas, TEA Ed."},{"key":"ref_21","first-page":"185","article-title":"Adaptaci\u00f3n espa\u00f1ola del \u201cEating Disorder Inventory Inventory\u201d (EDI) en una muestra de pacientes anor\u00e9xicas","volume":"3","author":"Guimera","year":"1987","journal-title":"Anal. Psiquiatr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.jpsychires.2014.04.005","article-title":"The role of leptin, melanocortin, and neurotrophin system genes on body weight in anorexia nervosa and bulimia nervosa","volume":"55","author":"Yilmaz","year":"2014","journal-title":"J. Psychiatr. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/164_2016_112","article-title":"OPRD1 Genetic Variation and Human Disease","volume":"247","author":"Crist","year":"2018","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1080\/15622975.2018.1517948","article-title":"Salivary opiorphin levels in anorexia nervosa: A case\u2014Control study","volume":"21","author":"Paszynska","year":"2020","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1002\/gepi.20486","article-title":"A powerful approach to sub-phenotype analysis in population-based genetic association studies","volume":"34","author":"Morris","year":"2010","journal-title":"Genet. Epidemiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"171268","DOI":"10.1016\/j.peptides.2024.171268","article-title":"Endogenous opiates and behavior: 2023","volume":"179","author":"Bodnar","year":"2024","journal-title":"Peptides"},{"key":"ref_27","first-page":"e10309","article-title":"The Risk of Substance Use Among Adolescents and Adults with Eating Disorders","volume":"12","author":"Eskander","year":"2020","journal-title":"Cureus"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/tpj.2013.30","article-title":"Genetic variation in OPRD1 and the response to treatment for opioid dependence with buprenorphine in European-American females","volume":"14","author":"Clarke","year":"2014","journal-title":"Pharmacogenomics J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.drugalcdep.2012.06.023","article-title":"Case\u2013control association analysis of polymorphisms in the delta-opioid receptor, OPRD1, with cocaine and opioid addicted populations","volume":"127","author":"Crist","year":"2013","journal-title":"Drug Alcohol. Depend."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1002\/ajmg.b.32087","article-title":"Genome-wide association analysis of eating disorder-related symptoms, behaviors, and personality traits","volume":"159B","author":"Boraska","year":"2012","journal-title":"Am. J. Med. Genet. Part B Neuropsychiatr. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1002\/erv.2899","article-title":"The effect of temperament and character on body dissatisfaction in women with bulimia nervosa: The role of low self-esteem and depression","volume":"30","author":"Jones","year":"2022","journal-title":"Eur. Eat. Disord. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/j.1600-0854.2008.00846.x","article-title":"Phe27Cys polymorphism alters the maturation and subcellular localization of the human \u03b4 opioid receptor","volume":"10","author":"Markkanen","year":"2009","journal-title":"Traffic"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1111\/fcp.12128","article-title":"The genetic influences on oxycodone response characteristics in human experimental pain","volume":"29","author":"Olesen","year":"2015","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.pnpbp.2018.08.028","article-title":"OPRD1 gene affects disease vulnerability and environmental stress in patients with heroin dependence in Han Chinese","volume":"89","author":"Huang","year":"2019","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.biopsych.2006.03.040","article-title":"The prevalence and correlates of eating disorders in the National Comorbidity Survey Replication","volume":"61","author":"Hudson","year":"2007","journal-title":"Biol. Psychiatry"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1038\/tpj.2014.53","article-title":"Impact of NEGR1 genetic variability on psychological traits of patients with eating disorders","volume":"15","author":"Gordillo","year":"2015","journal-title":"Pharmacogenomics J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e00784","DOI":"10.1002\/brb3.784","article-title":"Influence of TFAP2B and KCTD15 genetic variability on personality dimensions in anorexia and bulimia nervosa","volume":"7","author":"Albuquerque","year":"2017","journal-title":"Brain Behav."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1007\/s00787-013-0495-6","article-title":"BDNF genetic variability modulates psychopathological symptoms in patients with eating disorders","volume":"23","author":"Gordillo","year":"2014","journal-title":"Eur. Child Adolesc. Psychiatry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"145572","DOI":"10.1016\/j.gene.2021.145572","article-title":"Variants in the Obesity-Linked FTO gene locus modulates psychopathological features of patients with Anorexia Nervosa","volume":"783","author":"Flores","year":"2021","journal-title":"Gene"},{"key":"ref_40","first-page":"97","article-title":"Therapeutic Potential of Naltrexone in the Niche of Psychopharmacology","volume":"54","author":"Naguy","year":"2024","journal-title":"Psychopharmacol. Bull."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"106937","DOI":"10.1016\/j.cct.2022.106937","article-title":"An experimental protocol for a double-blind placebo-controlled evaluation of the effectiveness of oral naltrexone in management of adolescent eating disorders","volume":"122","author":"Roden","year":"2022","journal-title":"Contemp. Clin. Trials"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s40519-016-0345-x","article-title":"The comorbidity of personality disorders in eating disorders: A meta-analysis","volume":"22","author":"Martinussen","year":"2017","journal-title":"Eat. Weight. Disord."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/17\/5189\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:46:40Z","timestamp":1760111200000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/17\/5189"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,1]]},"references-count":42,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["jcm13175189"],"URL":"https:\/\/doi.org\/10.3390\/jcm13175189","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2024,9,1]]}}}