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The role of leptin, melanocortin, and neurotrophin system genes on body weight in anorexia nervosa and bulimia nervosa.

ABSTRACT: Although low weight is a key factor contributing to the high mortality in anorexia nervosa (AN), it is unclear how AN patients sustain low weight compared with bulimia nervosa (BN) patients with similar psychopathology. Studies of genes involved in appetite and weight regulation in eating disorders have yielded variable findings, in part due to small sample size and clinical heterogeneity. This study: (1) assessed the role of leptin, melanocortin, and neurotrophin genetic variants in conferring risk for AN and BN; and (2) explored the involvement of these genes in body mass index (BMI) variations within AN and BN.Our sample consisted of 745 individuals with AN without a history of BN, 245 individuals with BN without a history of AN, and 321 controls. We genotyped 20 markers with known or putative function among genes selected from leptin, melanocortin, and neurotrophin systems.There were no significant differences in allele frequencies among individuals with AN, BN, and controls. AGRP rs13338499 polymorphism was associated with lowest illness-related BMI in those with AN (p = 0.0013), and NTRK2 rs1042571 was associated with highest BMI in those with BN (p = 0.0018).To our knowledge, this is the first study to address the issue of clinical heterogeneity in eating disorder genetic research and to explore the role of known or putatively functional markers in genes regulating appetite and weight in individuals with AN and BN. If replicated, our results may serve as an important first step toward gaining a better understanding of weight regulation in eating disorders.

SUBMITTER: Yilmaz Z

PROVIDER: S-EPMC4191922 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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The role of leptin, melanocortin, and neurotrophin system genes on body weight in anorexia nervosa and bulimia nervosa.

Yilmaz Zeynep Z Kaplan Allan S AS Tiwari Arun K AK Levitan Robert D RD Piran Sara S Bergen Andrew W AW Kaye Walter H WH Hakonarson Hakon H Wang Kai K Berrettini Wade H WH Brandt Harry A HA Bulik Cynthia M CM Crawford Steven S Crow Scott S Fichter Manfred M MM Halmi Katherine A KA Johnson Craig L CL Keel Pamela K PK Klump Kelly L KL Magistretti Pierre P Mitchell James E JE Strober Michael M Thornton Laura M LM Treasure Janet J Woodside D Blake DB Knight Joanne J Kennedy James L JL

Journal of psychiatric research 20140416

<h4>Objective</h4>Although low weight is a key factor contributing to the high mortality in anorexia nervosa (AN), it is unclear how AN patients sustain low weight compared with bulimia nervosa (BN) patients with similar psychopathology. Studies of genes involved in appetite and weight regulation in eating disorders have yielded variable findings, in part due to small sample size and clinical heterogeneity. This study: (1) assessed the role of leptin, melanocortin, and neurotrophin genetic varia ...[more]

PMID: 24831852

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Project description:BackgroundEating disorders affect 13% of females and contribute to functional impairment and mortality, but few studies have identified risk factors that prospectively correlate with future onset of anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), and purging disorder (PD). Identifying risk factors specific to each eating disorder is critical for advancing etiologic knowledge and designing effective prevention programs.ObjectivesThis study examined whether weight suppression (the difference between a person's highest past weight at their adult height and their current weight) correlates with future onset of AN, BN, BED, and PD.MethodsData from 1165 young women with body image concerns (mean ± SD age: 21.9 ± 6.4 y) who completed annual diagnostic interviews over a 3-y follow-up period were examined. Logistic regression models evaluated the relation of baseline weight suppression to onset risk of each eating disorder controlling for age, dietary restraint, and intervention condition.ResultsElevated weight suppression predicted future onset of AN (OR: 1.36; 95% CI: 1.03, 1.80), BN (OR: 1.34; 95% CI: 1.11, 1.62), PD (OR: 1.46; 95% CI: 1.23, 1.74), and any eating disorder (OR: 1.32; 95% CI: 1.12, 1.56), but not BED (OR: 1.10; 95% CI: 0.89, 1.37). Highest past weight correlated with future onset of BN and PD but not onset of AN, BED, or any eating disorder, and baseline current weight was inversely related to future AN onset only, implying that women with the largest difference between their highest past weight and current weight are at greatest risk of eating disorders.ConclusionsThe results provide novel evidence that weight suppression correlates with future onset of eating disorders characterized by dietary restriction or compensatory weight control behaviors and suggest weight-suppressed women constitute an important risk group to target with selective prevention programs.These trials were registered at clinicaltrials.gov as NCT01126918 and NCT01949649.

Project description:ImportanceIndividuals with anorexia nervosa maintain extremely low body weights despite elevations in the circulating orexigenic hormone ghrelin. Whether circulating levels of endogenous ghrelin are associated with weight gain in anorexia nervosa is unknown.ObjectiveTo examine the association between baseline ghrelin and future weight change in individuals with anorexia nervosa.Design, setting, and participantsThis prospective cohort study was conducted between April 1, 2014, and March 31, 2020, in the US. Girls and women aged 10 to 22 years were recruited from the greater Boston area from community and area treatment centers, enrolled, and followed up for 18 months. Statistical analyses were performed between January and August 2022.ExposuresPresence or absence of anorexia nervosa and elevations in endogenous ghrelin.Main outcomes and measuresChanges in age- and sex-standardized body mass index percentiles from baseline to 9- and 18-month follow-up were the main outcomes of interest.ResultsA total of 68 girls and young women (11 [16%] Asian, 4 [6%] Hispanic or Latina, 51 [75%] White [non-Hispanic or Latina], and 2 [3%] other race or ethnicity), including 35 with anorexia nervosa and 33 healthy controls of similar Tanner stage, were included in this study. Anorexia nervosa and healthy control groups were not statistically different by race and ethnicity, Tanner stage, number completing follow-up visits, and the duration between baseline and follow-up visits. At baseline, individuals with anorexia nervosa were slightly older (median [IQR], 20.1 [18.5-21.0] vs 18.7 [14.7-19.4] years; P = .005), had lower body mass index percentiles (median [IQR], 2.4 [0.3-4.7] vs 52.9 [40.4-68.3]; P < .001), and had elevated circulating ghrelin area under the curve composite index (median [IQR], 1389.4 [1082.5-1646.4] vs 958.5 [743.0-1234.5] pg/mL; P = .003) compared with healthy individuals. In linear mixed-effects regression analyses, baseline ghrelin was associated with prospective weight gain after adjusting for diagnosis, age, race, and duration of follow-up (odds ratio, 2.35; 95% CI, 1.43-3.73; P = .004).Conclusions and relevanceIn this cohort study, endogenous ghrelin was associated with longitudinal weight gain in individuals with anorexia nervosa. Further studies are warranted to confirm this result and examine its potential clinical utility in treatment development.

Dataset Information

The role of leptin, melanocortin, and neurotrophin system genes on body weight in anorexia nervosa and bulimia nervosa.

Publications

The role of leptin, melanocortin, and neurotrophin system genes on body weight in anorexia nervosa and bulimia nervosa.

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