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Bulimia nervosa in a Canadian community sample: prevalence and comparison of subgroups

Paul Garfinkel et al.Jul 1, 1995

Clinical Psychology

Demography

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Fluoxetine After Weight Restoration in Anorexia Nervosa

B. Walsh et al.Jun 13, 2006

NOREXIA NERVOSA IS A SERIous psychiatric illness with substantial morbidity and a lifetime mortality arguably as high as that associated with any psychiatric illness. 1 A major contributor to the poor prognosis of this illness is the high rate of relapse following initial treatment.Despite successful weight restoration, 30% to 50% of patients require rehospitalization within 1 year of discharge. 2,3 This discouraging experience has prompted interest in interventions aimed at preventing deterioration following weight restoration.Patients with anorexia nervosa often exhibit symptoms of other psychiatric disorders, 4 such as depression and obsessive-compulsive disorder, which are responsive to antidepressant medication, suggesting that pharmacological interventions might be of use.Surpris-ingly, virtually all of the controlled trials of medication (most of which have been conducted during the initial phase of treatment when patients are underweight) have shown no benefit of medication compared with placebo. 5,6 Despite this lack of evidence of effectiveness, a substantial number of pa-See also p 2659 and Patient Page.

Internal Medicine

Clinical Psychology

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Relapse in anorexia nervosa: a survival analysis

J. Carter et al.Apr 21, 2004

Background. Knowledge about factors that predict relapse in anorexia nervosa (AN) is needed for the development of effective relapse prevention treatments and may also advance understanding of the psychopathology of AN. The aim of the present study was to examine the rate, timing and prediction of relapse in AN following weight restoration in a specialized in-patient treatment programme. Method. Fifty-one consecutive first-admission AN patients who were weight-restored following in-patient treatment participated in the study. Follow-up assessments were conducted a median of 15 months post-discharge. Relapse of AN was defined as a body mass index <17·5 for 3 consecutive months. Data were analysed using Kaplan–Meier survival analysis and Cox regression. Results. The overall rate of relapse was 35% and the mean survival time was 18 months. The highest risk period was from 6 to 17 months after discharge. Several significant predictors of relapse were identified: a history of suicide attempt; previous specialized treatment for an eating disorder; severity of obsessive–compulsive symptoms at presentation; excessive exercise immediately after discharge; and residual concern about shape and weight at discharge. Conclusions. There continues to be a significant risk of relapse among AN patients who remain well for the first year post-discharge. Several variables were shown to be associated with an elevated risk of relapse. These findings have implications for the development of initial treatments and relapse prevention strategies for AN.

Clinical Psychology

Public Health, Environmental And Occupational Health

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Features associated with excessive exercise in women with eating disorders

Hemal Shroff et al.Apr 24, 2006

Excessive exercise and motor restlessness are observed in a substantial number of patients with eating disorders. This trait has been studied extensively among animal models of activity anorexia nervosa (AN) and may hold particular interest as an endophenotype for AN. We explored features associated with excessive exercise across subtypes of eating disorders.Participants were female probands and affected female relatives from the multi-site international Price Foundation Genetic Studies with diagnoses of AN, bulimia nervosa (BN), and both AN and BN or eating disorder not otherwise specified (ED-NOS) (N=1,857). Excessive exercise was defined based on responses to the Structured Interview for Anorexic and Bulimic Disorders (SIAB).Among the eating disorder diagnostic groups, excessive exercise was most common among the purging subtype of AN. Individuals who reported excessive exercise also reported lower minimum BMI, younger age at interview, higher scores on anxiety, perfectionism, and eating disorder symptom measures, more obsessions and compulsions, and greater persistence.Excessive exercise may be associated particularly with the purging subtype of AN as well as with a constellation of anxious/obsessional temperament and personality characteristics among women with eating disorders.

Biochemistry

Clinical Psychology

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Subcallosal cingulate deep brain stimulation for treatment-refractory anorexia nervosa: a phase 1 pilot trial

Nir Lipsman et al.Mar 7, 2013

Background Anorexia nervosa is characterised by a chronic course that is refractory to treatment in many patients and has one of the highest mortality rates of any psychiatric disorder. Deep brain stimulation (DBS) has been applied to circuit-based neuropsychiatric diseases, such as Parkinson's disease and major depression, with promising results. We aimed to assess the safety of DBS to modulate the activity of limbic circuits and to examine how this might affect the clinical features of anorexia nervosa. Methods We did a phase 1, prospective trial of subcallosal cingulate DBS in six patients with chronic, severe, and treatment-refractory anorexia nervosa. Eligible patients were aged 20–60 years, had been diagnosed with restricting or binge-purging anorexia nervosa, and showed evidence of chronicity or treatment resistance. Patients underwent medical optimisation preoperatively and had baseline body-mass index (BMI), psychometric, and neuroimaging investigations, followed by implantation of electrodes and pulse generators for continuous delivery of electrical stimulation. Patients were followed up for 9 months after DBS activation, and the primary outcome of adverse events associated with surgery or stimulation was monitored at every follow-up visit. Repeat psychometric assessments, BMI measurements, and neuroimaging investigations were also done at various intervals. This trial is registered with ClinicalTrials.gov, number NCT01476540. Findings DBS was associated with several adverse events, only one of which (seizure during programming, roughly 2 weeks after surgery) was serious. Other related adverse events were panic attack during surgery, nausea, air embolus, and pain. After 9 months, three of the six patients had achieved and maintained a BMI greater than their historical baselines. DBS was associated with improvements in mood, anxiety, affective regulation, and anorexia nervosa-related obsessions and compulsions in four patients and with improvements in quality of life in three patients after 6 months of stimulation. These clinical benefits were accompanied by changes in cerebral glucose metabolism (seen in a comparison of composite PET scans at baseline and 6 months) that were consistent with a reversal of the abnormalities seen in the anterior cingulate, insula, and parietal lobe in the disorder. Interpretation Subcallosal cingulate DBS seems to be generally safe in this sample of patients with chronic and treatment-refractory anorexia nervosa. Funding Klarman Family Foundation Grants Program in Eating Disorders Research and Canadian Institutes of Health Research.

Internal Medicine

Clinical Psychology

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Comparison of 2 Family Therapies for Adolescent Anorexia Nervosa

W. Agras et al.Sep 24, 2014

IMPORTANCE Anorexia nervosa (AN) is a serious disorder with high rates of morbidity and mortality.Family-based treatment (FBT) is an evidence-based therapy for adolescent AN, but less than half of those who receive this approach recover.Hence, it is important to identify other approaches to prevent the development of the chronic form of AN for which there is no known evidence-based treatment.OBJECTIVE To compare FBT with systemic family therapy (SyFT) for the treatment of adolescent-onset AN. DESIGN, SETTING, AND PARTICIPANTSResearch in Anorexia Nervosa (RIAN) is a 2-group (FBT and SyFT) randomized trial conducted between September 2005 and April 2012.Interviewers were blinded to the treatment condition.A total of 564 adolescents receiving care at 6 outpatient clinics experienced in the treatment of AN were screened.Of these, 262 adolescents did not meet the inclusion criteria and 138 declined to participate; hence, 164 adolescents (aged 12-18 years) of both sexes meeting the criteria for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, AN (except for amenorrhea) were enrolled.Three participants were withdrawn from FBT and 7 were withdrawn from SyFT after serious adverse events occurred.INTERVENTIONS Two manualized family therapies with 16 one-hour sessions during 9 months.Family-based therapy focuses on the facilitation of weight gain, whereas SyFT addresses general family processes. MAIN OUTCOMES AND MEASURESThe primary outcomes were percentage of ideal body weight (IBW) and remission (Ն95% of IBW).The a priori hypothesis was that FBT would result in faster weight gain early in treatment and at the end of treatment (EOT).RESULTS There were no statistically significant differences between treatment groups for the primary outcome, for eating disorder symptoms or comorbid psychiatric disorders at the EOT or follow-up.Remission rates included FBT, 33.1% at the EOT and 40.7% at follow-up and SyFT, 25.3% and 39.0%, respectively.Family-based therapy led to significantly faster weight gain early in treatment, significantly fewer days in the hospital, and lower treatment costs per patient in remission at the EOT (FBT, $8963; SyFT, $18 005).An exploratory moderator analysis found that SyFT led to greater weight gain than did FBT for participants with more severe obsessive-compulsive symptoms. CONCLUSIONS AND RELEVANCEThe findings of this study suggest that FBT is the preferred treatment for adolescent AN because it is not significantly different from SyFT and leads to similar outcomes at a lower cost than SyFT.Adolescents with more severe obsessivecompulsive symptoms may receive more benefits with SyFT.

Internal Medicine

Clinical Psychology

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Genome-wide copy number variation association study in anorexia nervosa

Alicia Walker et al.Nov 12, 2024

Abstract This study represents the first large-scale investigation of rare (<1% population frequency) copy number variants (CNVs) in anorexia nervosa (AN). Large, rare CNVs are reported to be causally associated with anthropometric traits, neurodevelopmental disorders, and schizophrenia, yet their role in the genetic basis of AN is unclear. Using genome-wide association study (GWAS) array data from the Anorexia Nervosa Genetics Initiative (ANGI), which included 7414 AN case and 5044 controls, we investigated the association of 67 well-established syndromic CNVs and 178 pleiotropic disease-risk dosage-sensitive CNVs with AN. To identify novel CNV regions (CNVRs) that increase the risk of AN, we conducted genome-wide association studies with a focus on rare CNV-breakpoints (CNV-GWAS). We found no net enrichment of rare CNVs, either deletions or duplications, in AN, and none of the well-established syndromic or pleiotropic CNVs had a significant association with AN status. However, the CNV-GWAS found 21 nominally associated CNVRs that contribute to AN risk, covering protein-coding genes implicated in synaptic function, metabolic/mitochondrial factors, and lipid characteristics, like the CD36 (7q21.11) gene, which transports long-chain fatty acids into cells. CNVRs intersecting genes previously related to neurodevelopmental traits include deletions of NRXN1 intron 5 (2p16.3), IMMP2L (7q31.1), and PTPRD (9p23). Overall, given that our study is well powered to detect the CNV burden level reported for schizophrenia, we can conclude that rare CNVs have a limited role in the etiology of AN, as reported for bipolar disorder. Our nominal associations for the 21 discovered CNVRs are consistent with AN being a metabo-psychiatric trait, as demonstrated by the common genetic architecture of AN, and we provide association results to allow for replication in future research.

Genetics

Biochemistry

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Shared Genetic Risk between Eating Disorder- and Substance-Use-Related Phenotypes: Evidence from Genome-Wide Association Studies

Melissa Munn‐Chernoff et al.Aug 23, 2019

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa (BN) and problem alcohol use (genetic correlation [rg], twin-based=0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge-eating, AN without binge-eating, and a BN factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder (MDD). Total sample sizes per phenotype ranged from ~2,400 to ~537,000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg=0.18; false discovery rate q=0.0006), cannabis initiation and AN (rg=0.23; q<0.0001), and cannabis initiation and AN with binge-eating (rg=0.27; q=0.0016). Conversely, significant negative genetic correlations were observed between three non-diagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge-eating (rgs=-0.19 to -0.23; qs<0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for MDD loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships between these behaviors.

Genetics

Biochemistry

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The Anorexia Nervosa Genetics Initiative: Overview and Methods

Laura Thornton et al.Dec 15, 2017

Background: Genetic factors contribute to anorexia nervosa (AN); and the first genome-wide significant locus has been identified. We describe methods and procedures for the Anorexia Nervosa Genetics Initiative (ANGI), an international collaboration designed to rapidly recruit 13,000 individuals with AN as well as ancestrally matched controls. We present sample characteristics and the utility of an online eating disorder diagnostic questionnaire suitable for large-scale genetic and population research. Methods: ANGI recruited from the United States (US), Australia/New Zealand (ANZ), Sweden (SE), and Denmark (DK). Recruitment was via national registers (SE, DK); treatment centers (US, ANZ, SE, DK); and social and traditional media (US, ANZ, SE). All cases had a lifetime AN diagnosis based on DSM-IV or ICD-10 criteria (excluding amenorrhea). Recruited controls had no lifetime history of disordered eating behaviors. To assess the positive and negative predictive validity of the online eating disorder questionnaire (ED100K-v1), 109 women also completed the Structured Clinical Interview for DSM-IV (SCID), Module H. Results: Blood samples and clinical information were collected from 13,364 individuals with lifetime AN and from controls. Online diagnostic phenotyping was effective and efficient; the validity of the questionnaire was acceptable. Conclusions: Our multi-pronged recruitment approach was highly effective for rapid recruitment and can be used as a model for efforts by other groups. High online presence of individuals with AN rendered the Internet/social media a remarkably effective recruitment tool in some countries. ANGI has substantially augmented Psychiatric Genomics Consortium AN sample collection. ANGI is a registered clinical trial: clinicaltrials.gov NCT01916538; https://clinicaltrials.gov/ct2/show/NCT01916538?cond=Anorexia+Nervosa&draw=1&rank=3.

Genetics

Clinical Psychology

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Identifying tissues implicated in Anorexia Nervosa using Transcriptomic Imputation

Laura Huckins et al.Feb 14, 2018

Anorexia nervosa (AN) is a complex and serious eating disorder, occurring in ~1% of individuals. Despite having the highest mortality rate of any psychiatric disorder, little is known about the aetiology of AN, and few effective treatments exist. Global efforts to collect large sample sizes of individuals with AN have been highly successful, and a recent study consequently identified the first genome-wide significant locus involved in AN. This result, coupled with other recent studies and epidemiological evidence, suggest that previous characterizations of AN as a purely psychiatric disorder are over-simplified. Rather, both neurological and metabolic pathways may also be involved. In order to elucidate more of the system-specific aetiology of AN, we applied transcriptomic imputation methods to 3,495 cases and 10,982 controls, collected by the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED). Transcriptomic Imputation (TI) methods approaches use machine-learning methods to impute tissue-specific gene expression from large genotype data using curated eQTL reference panels. These offer an exciting opportunity to compare gene associations across neurological and metabolic tissues. Here, we applied CommonMind Consortium (CMC) and GTEx-derived gene expression prediction models for 13 brain tissues and 12 tissues with potential metabolic involvement (adipose, adrenal gland, 2 colon, 3 esophagus, liver, pancreas, small intestine, spleen, stomach). We identified 35 significant gene-tissue associations within the large chromosome 12 region described in the recent PGC-ED GWAS. We applied forward stepwise conditional analyses and FINEMAP to associations within this locus to identify putatively causal signals. We identified four independently associated genes; RPS26, C12orf49, SUOX, and RDH16. We also identified two further genome-wide significant gene-tissue associations, both in brain tissues; REEP5, in the dorso-lateral pre-frontal cortex (DLPFC; p=8.52x10-07), and CUL3, in the caudate basal ganglia (p=1.8x10-06). These genes are significantly enriched for associations with anthropometric phenotypes in the UK BioBank, as well as multiple psychiatric, addiction, and appetite/satiety pathways. Our results support a model of AN risk influenced by both metabolic and psychiatric factors.

Genetics

Clinical Psychology

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Genetics

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