Harry Brandt

Suicide attempts in anorexia nervosa.

Objective: To explore prevalence and patterns of suicidal attempts in persons with anorexia nervosa (AN). Methods: Participants were the first 432 persons (22 male, 410 female) enrolled in the NIH funded Genetics of Anorexia Nervosa Collaborative Study. All participants had current or lifetime AN. The participants ranged in age from 16 to 76 (mean = 30.4, SD = 11.3). Suicidal behavior and intent was assessed via the Diagnostic Interview for Genetic Studies. We compared frequency and severity of attempts across diagnostic subtypes and comorbidity, and personality features associated with the presence of suicide attempts in persons with AN. Results: About 16.9% of those with AN attempted suicide. Significantly fewer persons with the restricting subtype (7.4%) reported at least one attempt than those with purging AN (26.1%), AN with binge eating (29.3%), and a mixed picture of AN and bulimia nervosa (21.2%). After controlling for major depression, suicide attempts were associated with substance abuse, impulsive behaviors and traits, Cluster B personality disorders, panic disorder, and post-traumatic stress disorder as well as low self-directedness and eating disorder severity. Conclusions: Suicide attempts in AN are not uncommon, are frequently associated with the intention to die, occur less frequently in persons with the restricting subtype of the illness, and after controlling for depression are associated with a constellation of behaviors and traits associated with behavioral and affective dyscontrol. AN = anorexia nervosa; BN = bulimia nervosa; RAN = restricting anorexia nervosa; PAN = purging anorexia nervosa; AN(B) = binging anorexia nervosa; EDNOS = eating disorder not otherwise specified; ANBN = lifetime history of both AN and BN.

Comparison of 2 Family Therapies for Adolescent Anorexia Nervosa: A Randomized Parallel Trial

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 PARTICIPANTS Research 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 MEASURES The primary outcomes were percentage of ideal body weight (IBW) and remission (≥95% 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,

Influence of overanxious disorder of childhood on the expression of anorexia nervosa

8963; SyFT,

Association Study of 182 Candidate Genes in Anorexia Nervosa

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 RELEVANCE The 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 obsessive-compulsive symptoms may receive more benefits with SyFT. TRIAL REGISTRATION clinicaltrials.gov Identifier NCT00610753.

Symptom profile of major depressive disorder in women with eating disorders

OBJECTIVE Childhood anxiety often precedes the onset of anorexia nervosa (AN) and may mark a liability to the emergence of an eating disorder for some women. This study investigates the prevalence of overanxious disorder (OAD) among women with AN and explores how OAD impacts AN symptoms and personality traits. METHOD Participants were 637 women with AN who completed an eating disorders history, the Structured Clinical Interview for DSM-IV Axis I Disorders, and assessments for childhood anxiety, eating disorder attitudes, and associated personality traits. RESULTS Of 249 women (39.1%) reporting a history of OAD, 235 (94.4%) met criteria for OAD before meeting criteria for AN. In comparison to those without OAD, women with AN and OAD self-reported more extreme personality traits and attitudes and they engaged in more compensatory behaviors. CONCLUSION Among individuals with AN, those entering AN on a pathway via OAD present with more severe eating disorder pathology.

Substance use disorders in women with anorexia nervosa.

We performed association studies with 5,151 SNPs that were judged as likely candidate genetic variations conferring susceptibility to anorexia nervosa (AN) based on location under reported linkage peaks, previous results in the literature (182 candidate genes), brain expression, biological plausibility, and estrogen responsivity. We employed a case–control design that tested each SNP individually as well as haplotypes derived from these SNPs in 1,085 case individuals with AN diagnoses and 677 control individuals. We also performed separate association analyses using three increasingly restrictive case definitions for AN: all individuals with any subtype of AN (All AN: n = 1,085); individuals with AN with no binge eating behavior (AN with No Binge Eating: n = 687); and individuals with the restricting subtype of AN (Restricting AN: n = 421). After accounting for multiple comparisons, there were no statistically significant associations for any individual SNP or haplotype block with any definition of illness. These results underscore the importance of large samples to yield appropriate power to detect genotypic differences in individuals with AN and also motivate complementary approaches involving Genome‐Wide Association (GWA) studies, Copy Number Variation (CNV) analyses, sequencing‐based rare variant discovery assays, and pathway‐based analysis in order to make up for deficiencies in traditional candidate gene approaches to AN.

Temporal patterns of recovery across eating disorder subtypes.

Objective: Based on the well-documented association between eating disorders (EDs) and affective disorders, the patterns of comorbidity of EDs and major depressive disorder (MDD) were investigated. The temporal relation between EDs and MDD onset was analyzed to determine differences in the course and nature of MDD when experienced prior to versus after the onset of the ED. Method: Lifetime MDD and depressive symptoms were assessed in 1371 women with a history of ED. The prevalence of MDD was first explored across ED subtypes, and ages of onset of MDD and EDs were compared. Depressive symptoms were examined in individuals who developed MDD before and after ED onset. Results: The lifetime prevalence of MDD was 72.9%. Among those with lifetime MDD (n =963), 34.5% reported MDD onset before the onset of ED. Those who experienced MDD first reported greater psychomotor agitation (OR =1.53; 95%CI =1.14–2.06), and thoughts of own death (but not suicide attempts or ideation; OR =1.73; 95%CI =1.31–2.30). Among individuals who had MDD before ED, 26.5% had the MDD onset during the year before the onset of ED; 67% of individuals had the onset of both disorders within the same 3 year window. Conclusion: Clinicians treating individuals with new-onset ED or MDD should remain vigilant for the emergence of additional psychopathology, especially during the initial 3 year window following the onset of the first disorder.

The genetics of anorexia nervosa collaborative study: Methods and sample description.

OBJECTIVE We examined prevalence of substance use disorders (SUD) in women with: (1) anorexia nervosa (AN) restricting type (RAN); (2) AN with purging only (PAN); (3) AN with binge eating only (BAN); and (4) lifetime AN and bulimia nervosa (ANBN). Secondary analyses examined SUD related to lifetime purging behavior and lifetime binge eating. METHOD Participants (N = 731) were drawn from the International Price Foundation Genetic Studies. RESULTS The prevalence of SUD differed across AN subtypes, with more in the ANBN group reporting SUD than those in the RAN and PAN groups. Individuals who purged were more likely to report substance use than those who did not purge. Prevalence of SUD differed across lifetime binge eating status. DISCUSSION SUD are common in AN and are associated with bulimic symptomatology. Results underscore the heterogeneity in AN, highlighting the importance of screening for SUD across AN subtypes.

Factors associated with recovery from anorexia nervosa

Objective: To compare patterns of recovery in individuals with index episodes of anorexia nervosa (AN) and bulimia nervosa (BN). Method: Using Kaplan–Meier methods and Cox proportional hazards models, comparisons were conducted that were conditional on duration of eating disorder from onset and included a conservative recovery criterion of 3 asymptomatic years. Data collection was retrospective and from two of the international Price Foundation genetic studies on 901 individuals with eating disorders. Results: Using Kaplan–Meier methods, 11% of those with index AN and 10% of those with index BN met recovery criteria at 10 years. At 15 years, 16% of those with index AN and 25% of those with index BN met recovery criteria. In a Cox proportional hazards model the index BN group had three times the rate of recovery at 10–14 years (p=0.01) than the index AN group. Conclusions: Initially the probability of recovery was greater for those with index AN, but as the duration of the eating disorder lengthened those with BN had higher probabilities of recovery. Replication of these results with prospective data using similarly stringent recovery criteria and methods is required to confirm trends.

Habitual starvation and provocative behaviors: Two potential routes to extreme suicidal behavior in anorexia nervosa

OBJECTIVE Supported by National Institute of Mental Health (NIMH), this 12-site international collaboration seeks to identify genetic variants that affect risk for anorexia nervosa (AN). METHOD Four hundred families will be ascertained with two or more individuals affected with AN. The assessment battery produces a rich set of phenotypes comprising eating disorder diagnoses and psychological and personality features known to be associated with vulnerability to eating disorders. RESULTS We report attributes of the first 200 families, comprising 200 probands and 232 affected relatives. CONCLUSION These results provide context for the genotyping of the first 200 families by the Center for Inherited Disease Research. We will analyze our first 200 families for linkage, complete recruitment of roughly 400 families, and then perform final linkage analyses on the complete cohort. DNA, genotypes, and phenotypes will form a national eating disorder repository maintained by NIMH and available to qualified investigators.