Stephanie Zerwas

A genome-wide association study of anorexia nervosa

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge–purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10−7) in SOX2OT and rs17030795 (P=5.84 × 10−6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10−6) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10−6) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10−6), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

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.

Factors associated with recovery from anorexia nervosa

Previous studies of prognostic factors of anorexia nervosa (AN) course and recovery have followed clinical populations after treatment discharge. This retrospective study examined the association between prognostic factors--eating disorder features, personality traits, and psychiatric comorbidity--and likelihood of recovery in a large sample of women with AN participating in a multi-site genetic study. The study included 680 women with AN. Recovery was defined as the offset of AN symptoms if the participant experienced at least one year without any eating disorder symptoms of low weight, dieting, binge eating, and inappropriate compensatory behaviors. Participants completed a structured interview about eating disorders features, psychiatric comorbidity, and self-report measures of personality. Survival analysis was applied to model time to recovery from AN. Cox regression models were used to fit associations between predictors and the probability of recovery. In the final model, likelihood of recovery was significantly predicted by the following prognostic factors: vomiting, impulsivity, and trait anxiety. Self-induced vomiting and greater trait anxiety were negative prognostic factors and predicted lower likelihood of recovery. Greater impulsivity was a positive prognostic factor and predicted greater likelihood of recovery. There was a significant interaction between impulsivity and time; the association between impulsivity and likelihood of recovery decreased as duration of AN increased. The anxiolytic function of some AN behaviors may impede recovery for individuals with greater trait anxiety.

Quantifying and Predicting Mental Illness Severity in Online Pro-Eating Disorder Communities

Social media sites have struggled with the presence of emotional and physical self-injury content. Individuals who share such content are often challenged with severe mental illnesses like eating disorders. We present the first study quantifying levels of mental illness severity (MIS) in social media. We examine a set of users on Instagram who post content on pro-eating disorder tags (26M posts from 100K users). Our novel statistical methodology combines topic modeling and novice/clinician annotations to infer MIS in a users content. Alarmingly, we find that proportion of users whose content expresses high MIS have been on the rise since 2012 (13%/year increase). Previous MIS in a users content over seven months can predict future risk with 81% accuracy. Our model can also forecast MIS levels up to eight months in the future with performance better than baseline. We discuss the health outcomes and design implications as well as ethical considerations of this line of research.

The Changing "Weightscape" of Bulimia Nervosa

Standard treatments for bulimia nervosa are for patients with normal weight, but a growing proportion of patients are substantially overweight or obese. Weight-related medical problems require coordination with primary care and expanded treatment goals. Cognitive-behavioral therapy (CBT), the gold standard for bulimia nervosa, is fairly ineffective in reducing weight. Compatible strategies tested for binge-eating disorder include appetite awareness training, behavioral weight loss, and appetite-focused CBT. A combined approach may be essential to treatment adherence, as patients are seeking weight loss. Nonetheless, goals of therapy include setting realistic expectations and shifting the focus from weight to health. Therapy groups specifically for overweight bulimia nervosa patients help avoid negative body comparisons.

Course and predictors of maternal eating disorders in the postpartum period

OBJECTIVE To investigate course and predictors of eating disorders in the postpartum period. METHOD A total of 77,807 women, participating in the Norwegian Mother and Child Cohort Study (MoBa), completed questionnaires during pregnancy including items covering DSM-IV criteria for prepregnancy anorexia nervosa (AN), bulimia nervosa (BN), eating disorder not otherwise specified (EDNOS-P), and binge eating disorder (BED). Additional questionnaires were completed at 18 and 36 months postpartum. RESULTS Proportions of women remitting at 18 months and 36 months postpartum were 50% and 59% for AN, 39% and 30% for BN, 46% and 57% for EDNOS-P, and 45% and 42% for BED, respectively. However, disordered eating persisted in a substantial proportion of women meeting criteria for either full or subthreshold eating disorders. BN during pregnancy increased the risk for continuation of BN. BMI and psychological distress were significantly associated with course of BED. DISCUSSION This is the first large-scale population-based study on course of eating disorders in the postpartum period. The results indicated that disordered eating persists in a substantial proportion of women with prepregnancy eating disorders. Health care professionals working with women in this phase of life need to pay specific attention to eating disorder symptoms and behaviors.

The Head Bone's Connected to the Neck Bone: When Do Toddlers Represent Their Own Body Topography?

Developments in very young childrens topographic representations of their own bodies were examined. Sixty-one 20- and 30-month-old children were administered tasks that indexed the ability to locate specific body parts on oneself and knowledge of how ones body parts are spatially organized, as well as body-size knowledge and self-awareness. Age differences in performance emerged for every task. Body-part localization and body spatial configuration knowledge were associated; however, body topography knowledge was not associated with body-size knowledge. Both were related to traditional measures of self-awareness, mediated by their common associations with age. It is concluded that children possess an explicit, if rudimentary, topographic representation of their own bodys shape, structure, and size by 30 months of age.

The core symptoms of bulimia nervosa, anxiety, and depression: A network analysis

Bulimia nervosa (BN) is characterized by symptoms of binge eating and compensatory behavior, and overevaluation of weight and shape, which often co-occur with symptoms of anxiety and depression. However, there is little research identifying which specific BN symptoms maintain BN psychopathology and how they are associated with symptoms of depression and anxiety. Network analyses represent an emerging method in psychopathology research to examine how symptoms interact and may become self-reinforcing. In the current study of adults with a Diagnostic and Statistical Manual for Mental Disorders-Fourth Edition (DSM–IV) diagnosis of BN (N = 196), we used network analysis to identify the central symptoms of BN, as well as symptoms that may bridge the association between BN symptoms and anxiety and depression symptoms. Results showed that fear of weight gain was central to BN psychopathology, whereas binge eating, purging, and restriction were less central in the symptom network. Symptoms related to sensitivity to physical sensations (e.g., changes in appetite, feeling dizzy, and wobbly) were identified as bridge symptoms between BN, and anxiety and depressive symptoms. We discuss our findings with respect to cognitive–behavioral treatment approaches for BN. These findings suggest that treatments for BN should focus on fear of weight gain, perhaps through exposure therapies. Further, interventions focusing on exposure to physical sensations may also address BN psychopathology, as well as co-occurring anxiety and depressive symptoms.

Eating disorders and trauma history in women with perinatal depression.

OBJECTIVE Although the prevalence of perinatal depression (depression occurring during pregnancy and postpartum) is 10%, little is known about psychiatric comorbidity in these women. We examined the prevalence of comorbid eating disorders (ED) and trauma history in women with perinatal depression. METHODS A research questionnaire was administered to 158 consecutive patients seen in a perinatal psychiatry clinic during pregnancy (n=99) or postpartum (n=59). Measures included Structured Clinical Interview for DSM (SCID) IV-based questions for lifetime eating psychopathology and assessments of comorbid psychiatric illness including the State/Trait Anxiety Inventory (STAI), Patient Health Questionnaire (PHQ-9), Edinburgh Postnatal Depression Scale (EPDS), and Trauma Inventory. RESULTS In this cohort, 37.1% reported a putative lifetime ED history; 10.1% reported anorexia nervosa (AN), 10.1% reported bulimia nervosa (BN), 10.1% reported ED not otherwise specified-purging subtype (EDNOS-P), and 7.0% reported binge eating disorder (BED). Women with BN reported more severe depression (EPDS score, 19.1, standard deviation [SD 4.3], p=0.02; PHQ-severity 14.5, SD 7.4, p=0.02) than the referent group of women with perinatal depression and no ED history (EPDS 13.3, SD=6.1; PHQ 9.0, SD=6.2). Women with AN were more likely to report sexual trauma history than the referent group (62.5% vs. 29.3%, p<0.05), and those with BN were more likely report physical (50.0%, p<0.05) and sexual (66.7%, p<0.05) trauma histories. CONCLUSIONS ED histories were present in over one third of admissions to a perinatal psychiatry clinic. Women with BN reported more severe depression and histories of physical and sexual trauma. Screening for histories of eating psychopathology is important in women with perinatal depression.

Obstetric and gynecologic problems associated with eating disorders

OBJECTIVE This article summarizes the literature on obstetric and gynecologic complications associated with eating disorders. METHOD We performed a comprehensive search of the current literature on obstetric and gynecologic complications associated with eating disorders using PubMed. More recent randomized-controlled trials and larger data sets received priority. We also chose those that we felt would be the most relevant to providers. RESULTS Common obstetric and gynecologic complications for women with eating disorders include infertility, unplanned pregnancy, miscarriage, poor nutrition during pregnancy, having a baby with small head circumference, postpartum depression and anxiety, sexual dysfunction and complications in the treatment for gynecologic cancers. There are also unique associations by eating disorder diagnosis, such as earlier cessation of breastfeeding in anorexia nervosa; increased polycystic ovarian syndrome in bulimia nervosa; and complications of obesity as a result of binge eating disorder. DISCUSSION We focus on possible biological and psychosocial factors underpinning risk for poor obstetric and gynecological outcomes in eating disorders. Understanding these factors may improve both our understanding of the reproductive needs of women with eating disorders and their medical outcomes. We also highlight the importance of building multidisciplinary teams to provide comprehensive care to women with eating disorders during the reproductive years.