Sara E. Trace

The Genetics of Eating Disorders

Over the past decade, considerable advances have been made in understanding genetic influences on eating pathology. Eating disorders aggregate in families, and twin studies reveal that additive genetic factors account for approximately 40% to 60% of liability to anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). Molecular genetics studies have been undertaken to identify alterations in deoxyribonucleic acid sequence and/or gene expression that may be involved in the pathogenesis of disordered eating behaviors, symptoms, and related disorders and to uncover potential genetic variants that may contribute to variability of treatment response. This article provides an in-depth review of the scientific literature on the genetics of AN, BN, and BED including extant studies, emerging hypotheses, future directions, and clinical implications.

Schizophrenia Genetics: Where Next?

The purpose of this invited review is to summarize the state of genetic research into the etiology of schizophrenia (SCZ) and to consider options for progress. The fundamental uncertainty in SCZ genetics has always been the nature of the beast, the underlying genetic architecture. If this were known, studies using the appropriate technologies and sample sizes could be designed with an excellent chance of producing high-confidence results. Until recently, few pertinent data were available, and the field necessarily relied on speculation. However, for the first time in the complex and frustrating history of inquiry into the genetics of SCZ, we now have empirical data about the genetic basis of SCZ that implicate specific loci and that can be used to plan the next steps forward.

Body Dissatisfaction in Women Across the Lifespan: Results of the UNC-SELF and Gender and Body Image (GABI) Studies

To explore age differences in current and preferred silhouette and body dissatisfaction (current - preferred silhouette discrepancy) in women aged 25-89 years using figural stimuli [range: 1 (very small) to 9 (very large)]. Data were abstracted from two online convenience samples (N = 5868). t-tests with permutation-adjusted p-values examined linear associations between mean silhouette scores (current, preferred, discrepancy score) and age with/without stratification by body mass index (BMI). Modal current silhouette was 5; modal preferred silhouette was 4; mean discrepancy score was 1.8. There was no significant association between current silhouette and age, but a positive linear association between preferred silhouette and age remained after stratification by BMI. A significant inverse linear association of silhouette discrepancy score and age was found only prior to stratification by BMI. Body dissatisfaction exists in women across the adult life span and is influenced by BMI.

Effects of reducing the frequency and duration criteria for binge eating on lifetime prevalence of bulimia nervosa and binge eating disorder: Implications for DSM-5

OBJECTIVE We assessed the impact of reducing the binge eating frequency and duration thresholds on the diagnostic criteria for bulimia nervosa (BN) and binge eating disorder (BED). METHOD We estimated the lifetime population prevalence of BN and BED in 13,295 female twins from the Swedish Twin study of Adults: Genes and Environment employing a range of frequency and duration thresholds. External validation (risk to cotwin) was used to investigate empirical evidence for an optimal binge eating frequency threshold. RESULTS The lifetime prevalence estimates of BN and BED increased linearly as the frequency criterion decreased. As the required duration increased, the prevalence of BED decreased slightly. Discontinuity in cotwin risk was observed in BN between at least four times per month and at least five times per month. This model could not be fit for BED. DISCUSSION The proposed changes to the DSM-5 binge eating frequency and duration criteria would allow for better detection of binge eating pathology without resulting in a markedly higher lifetime prevalence of BN or BED.

An Evaluation of the Reliability and Construct Validity of Eating Disorder Measures in White and Black Women.

Most measures of eating disorder symptoms and risk factors were developed in predominantly White female samples. Yet eating disorders affect individuals of all racial and ethnic backgrounds. Black women appear more vulnerable to certain forms of eating pathology, such as binge eating, and less susceptible to other eating disorder symptoms and risk factors, such as body dissatisfaction, compared with their White peers. Despite concern that extant measures do not adequately assess eating concerns among Black women, the construct validity of scores on most of these measures has not been adequately examined within this population. This study included 2,208 Black and White women who completed the following: the Binge Eating Scale (BES), the Eating Disorder Diagnostic Scale (EDDS), the Eating Attitudes Test-26 (EAT-26), the Eating Disorder Inventory Body Dissatisfaction and Drive for Thinness subscales, the Bulimia Test-Revised (BULIT-R), the Multidimensional Body-Self Relations Questionnaire-Appearance Evaluation subscale (MBSRQ-AE), and the Objectified Body Consciousness Scale (OBCS). Most measures yielded internally consistent scores in both races. Confirmatory factor analyses indicated that loadings for some measures, including the EAT-26 and EDDS, were not invariant across groups and thus do not assess equivalent constructs in White and Black women. However, others, including the BULIT-R, BES, OBCS, and MBSRQ-AE, exhibited factorial invariance in both races. Results suggest scores are likely not equivalent across races for several popular measures of eating disorder symptoms and risk factors. Thus, it is recommended that researchers and clinicians obtain additional information regarding racial/cultural factors when using these instruments with Black women.

Sleep problems are associated with binge eating in women

OBJECTIVE We examined the association among current self-reported sleep problems, lifetime binge eating (BE), and current obesity in women from the Swedish Twin study of Adults: Genes and Environment. METHOD Logistic regression analyses were used to evaluate these associations in 3,790 women aged 20-47 years. RESULTS BE was reported by 244 (6.4%) women and was positively associated with not getting enough sleep (p < .015), sleeping poorly (p < .001), problems falling asleep (p < .001), feeling sleepy during work or free time (p < .001), and disturbed sleep (p < .001). These same sleep variables, as well as napping and being a night person, were also significantly associated with obesity. The associations between BE and sleep remained after accounting for obesity. DISCUSSION This investigation offers empirical support for an independent association between sleep problems and BE, which is likely due to complex psychological, biological, neuroendocrine, and metabolic factors.

A behavioral-genetic investigation of bulimia nervosa and its relationship with alcohol use disorder.

Bulimia nervosa (BN) and alcohol use disorder (AUD) frequently co-occur and may share genetic factors; however, the nature of their association is not fully understood. We assessed the extent to which the same genetic and environmental factors contribute to liability to BN and AUD. A bivariate structural equation model using a Cholesky decomposition was fit to data from 7241 women who participated in the Swedish Twin study of Adults: Genes and Environment. The proportion of variance accounted for by genetic and environmental factors for BN and AUD and the genetic and environmental correlations between these disorders were estimated. In the best-fitting model, the heritability estimates were 0.55 (95% CI: 0.37; 0.70) for BN and 0.62 (95% CI: 0.54; 0.70) for AUD. Unique environmental factors accounted for the remainder of variance for BN. The genetic correlation between BN and AUD was 0.23 (95% CI: 0.01; 0.44), and the correlation between the unique environmental factors for the two disorders was 0.35 (95% CI: 0.08; 0.61), suggesting moderate overlap in these factors. The findings from this investigation provide additional support that some of the same genetic factors may influence liability to both BN and AUD.

The expression of cytokines and chemokines in the blood of patients with severe weight loss from anorexia nervosa: An exploratory study

Anorexia nervosa (AN) is a serious, potentially life-threatening disorder characterized by severe weight loss, dysregulated eating, and often excessive exercise. While psychiatric illnesses such as depression are associated with increased levels of pro-inflammatory mediators, evidence for such disturbances in patients with AN has been less clear. In an exploratory study of possible disturbances in immune responses in AN, we assayed a panel of cytokines and chemokines in the blood of patients undergoing inpatient treatment, testing the hypothesis that metabolic disturbances in this disease would lead to a pattern of immune disturbances distinct from that of other psychiatric diseases. For this purpose, we evaluated patients by the Beck Depression Inventory-II (BDI-II) and the Eating Disorders Examination-Questionnaire and assessed cytokines and chemokines by enzyme-linked immunosorbent assays. Patients reported a moderate level of depression (mean BDI-II = 22.6) but exhibited few immunologic abnormalities of the kind associated with major depressive disorder [e.g., increased interleukin (IL)-6]; RANTES showed the most frequent elevations and was increased in 4 of the patients studied. Together, these findings suggest that features of AN such as loss of adipose tissue and excessive exercise may attenuate cytokine production and thus modulate the experience of illness that impacts on core features of disease.

Binge eating, body mass index, and gastrointestinal symptoms

OBJECTIVE Symptoms of both gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS) are frequently reported by individuals who binge eat. Higher body mass index (BMI) has also been associated with these disorders and with binge eating (BE). However, it is unknown whether BE influences GERD/IBS and how BMI might affect these associations. Thus, we examined the potential associations among BE, GERD, IBS, and BMI. METHODS Participants were from the Swedish Twin study of Adults: Genes and Environment (STAGE) and provided information on disordered eating behavior, BMI, gastrointestinal (GI) disorders, and commonly comorbid psychiatric and somatic illnesses. Key features of GERD and IBS were identified to create modified definitions of both disorders that were used as primary outcome variables. Logistic regression models were applied to determine the association between BE and each GERD/IBS both independently and in the context of BMI and other commonly comorbid psychiatric and somatic morbidities. RESULTS Prevalence estimates for GERD and IBS were higher among women than men (all p-values<.001). Only the association between BE and IBS was significant in both men and women after adjustment for BMI and the psychiatric/somatic morbidities. CONCLUSION BE appears to be an important consideration in the presence of IBS symptoms in both men and women, even when considering the impact of BMI and other commonly comorbid conditions. This association underscores the importance of routine assessment of BE in patients presenting with IBS to effectively manage the concurrent presentation of these problems.

Assessment of gene expression in peripheral blood using RNAseq before and after weight restoration in anorexia nervosa

We examined gene expression in the blood of six females with anorexia nervosa (AN) before and after weight restoration using RNAseq. AN cases (aged 19-39) completed clinical assessments and had blood drawn for RNA at hospital admission (T1,<~75% ideal body weight, IBW) and again at discharge (T2,≥ ~ 85% IBW). To examine the relationship between weight restoration and differential gene expression, normalized gene expression levels were analyzed using a paired design. We found 564 genes whose expression was nominally significantly different following weight restoration (p<0.01, 231 increased and 333 decreased). With a more stringent significance threshold (false discovery rate q<0.05), 67 genes met criteria for differential expression. Of the top 20 genes, CYP11A1, C16orf11, LINC00235, and CPA3 were down-regulated more than two-fold after weight restoration while multiple olfactory receptor genes (OR52J3, OR51L1, OR51A4, and OR51A2) were up-regulated more than two-fold after weight restoration. Pathway analysis revealed up-regulation of two broad pathways with largely overlapping genes, one related to protein secretion and signaling and the other associated with defense response to bacterial regulation. Although results are preliminary secondary to a small sample size, these data provide initial evidence of transcriptional alterations during weight restoration in AN.