Genomics of body fat percentage may contribute to sex bias in anorexia nervosa.
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ABSTRACT:
SUBMITTER: Hubel C
PROVIDER: S-EPMC6751355 | biostudies-literature | 2019 Sep
REPOSITORIES: biostudies-literature
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Genomics of body fat percentage may contribute to sex bias in anorexia nervosa.
Hübel Christopher C Gaspar Héléna A HA Coleman Jonathan R I JRI Finucane Hilary H Purves Kirstin L KL Hanscombe Ken B KB Prokopenko Inga I Graff Mariaelisa M Ngwa Julius S JS Workalemahu Tsegaselassie T O'Reilly Paul F PF Bulik Cynthia M CM Breen Gerome G
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 20181228 6
Anorexia nervosa (AN) occurs nine times more often in females than in males. Although environmental factors likely play a role, the reasons for this imbalanced sex ratio remain unresolved. AN displays high genetic correlations with anthropometric and metabolic traits. Given sex differences in body composition, we investigated the possible metabolic underpinnings of female propensity for AN. We conducted sex-specific GWAS in a healthy and medication-free subsample of the UK Biobank (n = 155,961), ...[more]
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Project description:The aim of this paper was to conduct a systematic review of body fat distribution before and after partial and complete weight restoration in individuals with anorexia nervosa. Literature searches, study selection, method development and quality appraisal were performed independently by two authors, and data was synthesized using a narrative approach. Twenty studies met the inclusion criteria and were consequently analyzed. The review had five main findings. First, during anorexia nervosa adolescent females lose more central body fat, while adult females more peripheral fat. Second, partial weight restoration leads to greater fat mass deposition in the trunk region than other body regions in adolescent females. Third, after short-term weight restoration, whether partial or complete, adults show a central adiposity phenotype with respect to healthy age-matched controls. Fourth, central fat distribution is associated with increased insulin resistance, but does not adversely affect eating disorder psychopathology or cause psychological distress in female adults. Fifth, the abnormal central fat distribution seems to normalize after long-term maintenance of complete weight restoration, indicating that preferential central distribution of body fat is a transitory phenomenon. However, a discrepancy in the findings has been noted, especially between adolescents and adults; besides age and gender, these appear to be related to differences in the methodology and time of body composition assessments. The PROSPERO Registry-Anorexia Nervosa and Body Fat Distribution: A Systematic Review (CRD42014008738).
| S-EPMC4179194 | biostudies-literature
Project description:IntroductionBiological sex influences both overall adiposity and fat distribution. Further, testosterone and sex hormone binding globulin (SHBG) influence adiposity and metabolic function, with differential effects of testosterone in men and women. Here, we aimed to perform sex-stratified genome-wide association studies (GWAS) of body fat percentage (BFPAdj) (adjusting for testosterone and sex hormone binding globulin (SHBG)) to increase statistical power.MethodsGWAS were performed in white British individuals from the UK Biobank (157,937 males and 154,337 females). To avoid collider bias, loci associated with SHBG or testosterone were excluded. We investigated association of BFPAdj loci with high density cholesterol (HDL), triglyceride (TG), type 2 diabetes (T2D), coronary artery disease (CAD), and MRI-derived abdominal subcutaneous adipose tissue (ASAT), visceral adipose tissue (VAT) and gluteofemoral adipose tissue (GFAT) using publicly available data from large GWAS. We also performed 2-sample Mendelian Randomization (MR) using identified BFPAdj variants as instruments to investigate causal effect of BFPAdj on HDL, TG, T2D and CAD in males and females separately.ResultsWe identified 195 and 174 loci explaining 3.35% and 2.60% of the variation in BFPAdj in males and females, respectively at genome-wide significance (GWS, p<5x10-8). Although the direction of effect at these loci was generally concordant in males and females, only 38 loci were common to both sexes at GWS. Seven loci in males and ten loci in females have not been associated with any adiposity/cardiometabolic traits previously. BFPAdj loci generally did not associate with cardiometabolic traits; several had paradoxically beneficial cardiometabolic effects with favourable fat distribution. MR analyses did not find convincing supportive evidence that increased BFPAdj has deleterious cardiometabolic effects in either sex with highly significant heterogeneity.ConclusionsThere was limited genetic overlap between BFPAdj in males and females at GWS. BFPAdj loci generally did not have adverse cardiometabolic effects which may reflect the effects of favourable fat distribution and cardiometabolic risk modulation by testosterone and SHBG.
| S-EPMC10585153 | biostudies-literature
Project description:ObjectiveTo compare bone mineral density (BMD) and body composition among adolescents: (a) with atypical anorexia nervosa (AAN) versus anorexia nervosa (AN) and (b) those with and without a prior history of overweight.MethodElectronic medical records of patients 9-20 years with AN or AAN who underwent dual-energy x-ray absorptiometry scans were retrospectively reviewed and analyzed.ResultsA total of 286 adolescents with AN or AAN were included. In linear regression models, AAN was associated with greater Z-scores in whole body bone mineral content (BMC, B = 0.88, p < 0.001), lumbar spine BMD (B = 0.79, p = 0.002), femoral neck BMD (B = 0.670, p = 0.009); fat mass index (B = 1.33, p = 0.003), and lean body mass index (LBMI, B = 1.10, p < 0.001) compared to AN, adjusting for age, sex, and duration of illness. A prior overweight history was associated with greater Z-scores in whole body BMC; lumbar spine BMD, total hip BMD, femoral neck BMD, and LBMI.DiscussionAdolescents with AAN had higher BMD Z-scores than adolescents with AN; adolescents with a prior overweight history had greater BMD Z-scores than adolescents without a prior overweight history. These findings may inform clinical guidelines for the medical management of AAN.
| S-EPMC6613651 | biostudies-literature
Project description:Individuals with anorexia nervosa (AN) typically display anxious traits prior to the onset of food avoidance and weight loss that characterize the disorder. Meal associated anxiety is an especially common clinical feature in these patients, and heightened sensitivity to sympathetically mediated interoceptive sensations has also been observed. However, it remains unclear how heightened interoceptive sensitivity relates to experiences of anxiety before and after meals. To investigate this relationship, we experimentally induced anxiety and panic symptoms with isoproterenol, a peripheral sympathetic agonist similar to adrenaline, across several different conditions: during panic provocation, during anticipation of a 1,000 Calorie meal, and after meal consumption. Fifteen AN and 15 age- and sex-matched healthy comparisons received bolus infusions of isoproterenol and saline in a double-blinded, randomized design. Participants rated anxiety symptoms after each infusion, completed panic rating scales, and traced the location of perceived palpitations on a manikin to index interoceptive "body map" representation. The AN group reported significantly elevated anxiety relative to healthy comparisons during infusions before and after the meal, but surprisingly, not during panic provocation. These symptoms were accompanied by geographical differences in patterns of perceived heartbeat sensations across each condition. In particular, the AN group localized heartbeat sensations disproportionately to the chest during meal related saline infusions, when no cardiorespiratory modulation actually occurred. The AN group also showed a trend toward higher panic attack rates during the meal anticipation period. Correcting for anxiety levels reported during saline infusions abolished group differences in anxiety change across all conditions, suggesting a significant contribution of anxious traits in AN. The observation of meal related "visceral illusions" provides further evidence that AN is associated with abnormal interoceptive representation of the heartbeat and suggests that meal consumption, particularly when anticipated, preferentially alters the processing of interoception related signals in AN.
| S-EPMC6160545 | biostudies-literature
Project description:ObjectiveReward and punishment sensitivity are known to be altered in anorexia nervosa (AN). Most research has examined these constructs separately although motivated behavior is influenced by considering both the potential for reward and risk of punishment. The present study sought to compare the relative balance of reward and punishment sensitivity in AN versus healthy controls (HCs) and examine whether motivational bias is associated with AN symptoms and treatment outcomes.MethodsAdolescents and adults with AN (n = 262) in a partial hospitalization program completed the Eating Disorders Examination Questionnaire (EDE-Q), Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) scales, and Sensitivity to Punishment/Sensitivity to Reward Questionnaire (SPSRQ) at admission and discharge. HCs (HC; n = 90) completed the BIS/BAS and SPSRQ. Motivational Bias Scores were calculated to reflect the dominance of reward versus punishment sensitivity.ResultsIndividuals with AN demonstrated significantly greater bias toward punishment sensitivity than HC. In AN, a bias toward punishment was associated with higher EDE-Q Global score at admission. Change in motivational bias during treatment predicted EDE-Q Global scores, but not BMI, at discharge, with greater increases in reward sensitivity or greater decreases in punishment sensitivity during treatment predicting lower eating pathology. Similar findings were observed using the BIS/BAS and SPSRQ.DiscussionChange in motivational bias during treatment is associated with improved outcomes in AN. However, it appears that much of the change in motivational bias can be attributed to changes in punishment sensitivity, rather than reward sensitivity. Future research should examine the mechanisms underlying punishment sensitivity decreases during treatment.Public significanceSensitivity to reward and punishment may be important treatment targets for individuals with anorexia nervosa (AN). To date, most research has considered reward and punishment sensitivity separately, rather than examining their relationship to each other. We found that the balance of reward and punishment sensitivity (i.e., motivational bias) differs between healthy controls and those with AN and that this bias is associated with eating disorder symptoms and treatment outcome.
| S-EPMC10947895 | biostudies-literature
Project description:Anorexia nervosa (AN) is a psychiatric disorder with an estimated heritability of around 70%. Although the largest genome-wide association study meta-analysis on AN identified independent loci-conferring risk to the disorder, the molecular mechanisms underlying the genetic basis of AN remains to be elucidated. To explore AN, we ran a transcriptome profiling in peripheral blood mononuclear cells of 15 AN subjects and 15 healthy controls. We validated our mean results in a mouse model of chronic food restriction mimicking several aspects of AN. Through this exploratory study we identified 673 significantly differentially expressed genes in AN. Among these genes, we identified the Vanin-1 (Vnn1) gene that appears to play a major role in the regulation of multiple metabolic pathways. We confirmed an underexpression of Vnn1, especially in the liver, in a mouse model of chronic food restriction. These results indicate that quantitative food restriction affects Vnn1 expression, suggesting that this gene may contribute to the anorexic phenotype in the chronic food restriction mouse model as well as in patients affected by AN. We believe that this report highlights promising candidate genes and gene pathways for AN and reveals Vnn1 as a biomarker that may be used as molecular targets to predict and/or to understand AN.
2023-10-31 | GSE245978 | GEO
Project description:ObjectiveGenome-wide association studies have identified multiple genomic regions associated with anorexia nervosa. No genome-wide studies of other eating disorders, such as bulimia nervosa and binge-eating disorder, have been performed, despite their substantial heritability. Exploratively, we aimed to identify traits that are genetically associated with binge-type eating disorders.MethodWe calculated genome-wide polygenic scores for 269 trait and disease outcomes using PRSice v2.2 and their association with anorexia nervosa, bulimia nervosa, and binge-eating disorder in up to 640 cases and 17,050 controls from the UK Biobank. Significant associations were tested for replication in the Avon Longitudinal Study of Parents and Children (up to 217 cases and 3,018 controls).ResultsIndividuals with binge-type eating disorders had higher polygenic scores than controls for other psychiatric disorders, including depression, schizophrenia, and attention deficit hyperactivity disorder, and higher polygenic scores for body mass index.DiscussionOur findings replicate some of the known comorbidities of eating disorders on a genomic level and motivate a deeper investigation of shared and unique genomic factors across the three primary eating disorders.
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Project description:BackgroundA diagnostic criterion of Anorexia Nervosa (AN) is body image disturbance. Body exposure therapy is a widely used approach to treat this; however, it is unclear which part of body exposure therapy is relevant for regaining a realistic perspective on the own body. This study aimed to examine the role of the attentional bias (AB), which AN patients exhibit to the most disliked parts of their body. Additionally, emotional responses to the body exposure sessions were examined.MethodsParticipants were adolescent girls with a diagnosis of AN, who were randomly assigned to either an intervention (INT) or a treatment-as-usual (TAU) group. Both groups completed a pre and a post session, which included the completion of questionnaires to measure AN-psychopathology. The INT group received four sessions of a computer-based body exposure between the pre and the post session. The viewing pattern was recorded before and after each intervention session via an eyetracking (ET) device, as were emotional response scores on a visual analog scale (VAS; anxiety and disgust). The TAU group did not receive the intervention, but viewing patterns were recorded during the pre and the post session. All participants were asked to list their three least favorite body parts to be able to subsequently assess the AB.ResultsFifty-eight adolescent girls with AN participated in the study. There were no differences in psychopathology pre to post session, as measured by administered questionnaires. The existence of an AB could be replicated, but there was no significant reduction in the AB pre to post session in the INT group, nor was there an interaction between group and time. Also, no changes in the AB were found within and between sessions in the INT group. Anxiety scores reduced significantly across sessions while disgust scores were significantly higher post session than they were pre session.ConclusionsWhile the existence of an AB was demonstrated, the carried-out body exposures were neither sufficient to reduce the AB nor the psychopathology; nevertheless, a significant decrease in anxiety levels showed the usefulness of the exposure sessions. Future research might benefit from more exposure sessions and incorporating AB modification training (ABMT).
| S-EPMC11683846 | biostudies-literature
Project description:One key symptom of anorexia nervosa (AN) is body image distortion (BID). For example, AN patients who are asked to perform body size estimation tasks tend to overestimate their body size; this is thought to indicate a distortion of the perceptive component of body image. Although BID is an important treatment objective, only few treatment approaches explicitly target body image, and even fewer target the perceptive component. Moreover, very little is known about how patients' perceptive body image changes after treatment and related weight gain. Consequently, we investigated changes of the perceptive BID in adolescent AN patients at the beginning (T1) and the end (T2) of inpatient treatment using a body size estimation task. A total of 38 AN patients performed the test for Body Image Distortion in Children and Adolescents (BID-CA) within the first 2 weeks of inpatient treatment and at the end of treatment. The results were compared to 48 healthy control (HC) participants performing the same task once. At T1, AN patients overestimated their body size more than HC, i.e., a total overestimation of 33% in AN patients vs. 11% in HC. At T2, AN patients overestimated their arm size to the same degree that they did at TI, but overestimations for the thigh and waist were reduced, and their overestimations for the waist no longer differed from the HC group. Thus, after treatment, AN patients were partly able to more realistically estimate their body size. Several factors may have influenced the observed changes in body size estimation, including task repetition, deliberate adjustment, growing into their preexisting perceptive body image through weight gain, as well as targeted and non-specific psychotherapeutic treatments. In conclusion, the perceptive BID in adolescent AN patients is persistent but also modifiable. Although diverse factors presumably play a role in changing BID, these findings suggest that AN patients may benefit from targeted treatment of BID.
| S-EPMC6803517 | biostudies-literature
Project description:BackgroundBody image disorders are well documented in anorexia nervosa (AN); however, knowledge of interoceptive awareness (IA) in this population remains poor. This descriptive study investigated whether and how the representation of the interior of the body may have an impact on IA.MethodsThe representations and knowledge of the body interior were evaluated with a drawing task in 34 women with AN and 34 healthy controls (HCs). A lexicometric analysis was performed on the vocabulary used to describe the drawn body parts in a structured interview. It was assumed that the conceptual representation of the body interior could be affected by or influence IA. Thus, the relationship between IA, measured with the heartbeat task and the ischemia-induction test, and the drawings was explored. Other scales, such as those of body shape, awareness or satisfaction, were used to assess affective representations of the body.ResultsThe drawing, lexicometric and IA results were similar in the two groups. No correlations were found among IA, body representation scores and representation level of body interior. Only the representation of bones by the AN group was significantly different.DiscussionIncreased visual attention to the skeleton or greater awareness of bone health could explain the stronger representation of bones in the AN group. The psychophysical therapy received by some AN participants (73%) did not seem to have influenced IA. Our results do not support a relationship between IA and the representation of the body interior.Clinical trial registration:https://clinicaltrials.gov/, identifier NCT03988218.
| S-EPMC11229774 | biostudies-literature