Associations between dimensions of anorexia nervosa and obsessive-compulsive disorder: An examination of personality and psychological factors in patients with anorexia nervosa.

OBJECTIVE: Anorexia nervosa (AN) and obsessive-compulsive disorder (OCD) are highly comorbid. However, the factors that account for this comorbidity are poorly understood. We examined the core dimensions of AN and OCD and psychological and personality factors shared by both disorders. METHOD: In path analyses (N = 732 women with either current AN or recovered from AN), we examined which factors were uniquely and independently associated with the core dimensions of AN and OCD. We also examined recovery from AN as a moderator. RESULTS: When individuals with AN reported greater concern over mistakes, they endorsed more severity in both AN and OCD core dimensions. These unique associations existed above and beyond all other transdiagnostic personality and psychological factors and regardless of AN recovery status. CONCLUSIONS: Concern over mistakes partially accounts for severity in the core dimensions of both AN and OCD. Concern over mistakes may represent an important target in the aetiology of AN and OCD.

Knowledge and practice of eating disorders among a group of adolescent dental patients.

OBJECTIVES: The objectives are to ascertain how much is known about the eating disorders of bulimia and anorexia nervosa in a group of female adolescents, to determine if they had practiced behaviors consistent with these eating disorders, and to determine if there was a disconnect with actual and perceived healthy weight status. STUDY DESIGN: 126 research subjects completed a survey instrument. Embedded in the eighteen question survey were the five "SCOFF" questions, to determine if an eating disorder may exist. The BMI percentile was obtained for all participants. RESULTS: 18.3% of the research sample may have an eating disorder as predicted by the SCOFF questions. Of those with a suspected eating disorder, only 38% could correctly identify the best description of bulimia nervosa and 50% for anorexia nervosa. The BMI percentiles were higher in the group suspected of having an eating disorder CONCLUSIONS: Young adolescent females are at risk for eating disorders. Educational interventions should be directed at this young age group. If the at-risk individuals knew more about the consequences of these disorders, they may be less likely to practice the behaviors.

Association of candidate genes with phenotypic traits relevant to anorexia nervosa.

This analysis is a follow-up to an earlier investigation of 182 genes selected as likely candidate genetic variations conferring susceptibility to anorexia nervosa (AN). As those initial case-control results revealed no statistically significant differences in single nucleotide polymorphisms, herein, we investigate alternative phenotypes associated with AN. In 1762 females, using regression analyses, we examined the following: (i) lowest illness-related attained body mass index; (ii) age at menarche; (iii) drive for thinness; (iv) body dissatisfaction; (v) trait anxiety; (vi) concern over mistakes; and (vii) the anticipatory worry and pessimism versus uninhibited optimism subscale of the harm avoidance scale. After controlling for multiple comparisons, no statistically significant results emerged. Although results must be viewed in the context of limitations of statistical power, the approach illustrates a means of potentially identifying genetic variants conferring susceptibility to AN because less complex phenotypes associated with AN are more proximal to the genotype and may be influenced by fewer genes.

Absence of association between specific common variants of the obesity-related FTO gene and psychological and behavioral eating disorder phenotypes.

Extensive population-based genome-wide association studies have identified an association between the FTO gene and BMI; however, the mechanism of action is still unknown. To determine whether FTO may influence weight regulation through psychological and behavioral factors, seven single-nucleotide polymorphisms (SNPs) of the FTO gene were genotyped in 1,085 individuals with anorexia nervosa (AN) and 677 healthy weight controls from the international Price Foundation Genetic Studies of Eating Disorders. Each SNP was tested in association with eating disorder phenotypes and measures that have previously been associated with eating behavior pathology: trait anxiety, harm-avoidance, novelty seeking, impulsivity, obsessionality, compulsivity, and concern over mistakes. After appropriate correction for multiple comparisons, no significant associations between individual FTO gene SNPs and eating disorder phenotypes or related eating behavior pathology were identified in cases or controls. Thus, this study found no evidence that FTO gene variants associated with weight regulation in the general population are associated with eating disorder phenotypes in AN participants or matched controls.

Substance use disorders in women with anorexia nervosa.

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.

Association study of 182 candidate genes in 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.

A Double-Blind, Randomized Pilot Trial of Chromium Picolinate for Overweight Individuals with Binge-Eating Disorder: Effects on Glucose Regulation.

PURPOSE: Chromium treatment has been shown to improve glucose regulation in some populations. The purpose of this study was to evaluate whether chromium picolinate (CrPic) supplementation improves glucose regulation in overweight individuals with binge-eating disorder (BED). METHODS: In this double-blinded randomized pilot trial, participants (N = 24) were randomized to high (HIGH, 1000 mcg/day, n = 8) or moderate (MOD, 600 mcg/day, n = 9) dose of CrPic or placebo (PL, n = 7) for 6 months. Participants completed an oral glucose tolerance test (OGTT) at baseline, 3 months, and 6 months. Fixed effects models were used to estimate mean change in glucose area under the curve (AUC), insulinAUC, and insulin sensitivity index (ISI). RESULTS: Results revealed a significant group and time interaction (p < 0.04) for glucoseAUC, with glucoseAUC increasing significantly in the PL group (p < 0.02) but decreasing significantly in the MOD group (p < 0.03) at 6 months. InsulinAUC increased significantly over time (main effect, p < 0.02), whereas ISI decreased significantly over time (main effect, p < 0.03). CONCLUSION: As anticipated, a moderate dose of CrPic was associated with improved glycemic control, whereas PL was associated with decreased glycemic control. It was unexpected that the improved glycemic control seen in the MOD dose group was not seen in the HIGH dose group. However, although participants randomized to the HIGH dose group did not have improved glycemic control, they had better glycemic control than participants randomized to the PL group. These findings support the need for larger trials.

Practice Parameter for the Assessment and Treatment of Children and Adolescents With Eating Disorders.

(Reprinted from the Journal of the American Academy of Child & Adolescent Psychiatry 2015;54(5):412-425 with permission from the Academy).

Practice parameter for the assessment and treatment of children and adolescents with eating disorders.

This Practice Parameter reviews evidence-based practices for the evaluation and treatment of eating disorders in children and adolescents. Where empirical support is limited, clinical consensus opinion is used to supplement systematic data review. The Parameter focuses on the phenomenology of eating disorders, comorbidity of eating disorders with other psychiatric and medical disorders, and treatment in children and adolescents. Because the database related to eating disorders in younger patients is limited, relevant literature drawn from adult studies is included in the discussion.

Pharmacological approaches to the management of binge eating disorder.

In the USA, binge eating disorder (BED) is the most common eating disorder, with a lifetime prevalence of ~3.5 % in adult women, 2.0 % in adult men, and 1.6 % in adolescents. BED is characterized by frequent episodes of binge eating that are accompanied by a sense of loss of control over eating and result in marked psychological distress. BED is highly co-morbid with obesity and with depression and other psychiatric conditions, and it is associated with substantial role impairment. Currently, there are no US FDA-approved pharmacological treatments for BED. Animal and human studies implicate underlying dysregulation in dopamine, opioid, acetylcholine, and serotonin neurocircuitry within brain reward regions in the pathogenesis and maintenance of BED. To date, the efficacy of various agents that target these and other neurotransmitter systems involved in motivated feeding behavior, mood regulation, and impulse control have been investigated in the treatment of BED. Several antidepressant and anticonvulsant agents have demonstrated efficacy in reducing binge eating frequency, but only in limited cases have these effects resulted in patients achieving abstinence, which is the primary goal of treatment; they also range from less (fluvoxamine) to more (topiramate) effective in achieving weight loss that is both clinically meaningful and significantly greater than placebo. Collectively, the literature on pharmacological treatment approaches to BED is limited in that very few agents have been studied in multiple, confirmatory trials with adequate follow up, and almost none have been evaluated in large patient samples that are diverse with respect to age, sex, and ethnicity. In addition, prior trials have not adequately addressed, through study design, the high placebo response commonly observed in this patient population. Several novel agents are in various phases of testing, and recent animal studies focusing on glutamate-signaling circuits linking the amygdala to the lateral hypothalamus offer new avenues for exploration and potential therapeutic development. Studies of newly FDA-approved medications for long-term obesity treatment and further explorations of dietary supplements and neutraceuticals with appetite- and mood-altering properties may also be worthwhile.

An open trial of olanzapine in anorexia nervosa.

BACKGROUND: Recent reports raise the possibility that olanzapine can assist weight gain and improve behavioral symptoms during refeeding in anorexia nervosa. METHOD: Seventeen DSM-IV anorexia nervosa subjects hospitalized between May 1999 and October 2000 were enrolled in open-label treatment with olanzapine for up to 6 weeks. Baseline weight and symptoms were compared to patients' status at the end of treatment. RESULTS: Olanzapine administration was associated with a significant reduction in depression, anxiety, and core eating disorder symptoms, and a significant increase in weight. A comparison with our historical data suggests that subjects in this study had a significantly greater decrease in depression. CONCLUSION: These data lend support to the possibility that olanzapine may be useful in treating anorexia nervosa. However, a controlled trial is necessary to demonstrate that olanzapine is efficacious.

A double-blind, randomized pilot trial of chromium picolinate for binge eating disorder: results of the Binge Eating and Chromium (BEACh) study.

OBJECTIVE: Chromium treatment has been shown to improve mood, appetite, and glucose regulation in various psychiatric and medical patient populations. The authors propose that chromium may be useful in the treatment of binge eating disorder (BED). METHOD: Twenty-four overweight adults with BED were enrolled in a 6-month double-blind placebo-controlled trial and randomly assigned to receive either 1000mcg chromium/day ("high dose"; n=8) or 600mcg chromium/day ("moderate dose"; n=9) as chromium picolinate or placebo (n=7). Mixed linear regression models were used to estimate mean change in binge frequency and related psychopathology, weight, symptoms of depression, and fasting glucose. RESULTS: Fasting glucose was significantly reduced in both chromium groups compared to the placebo group; similarly, numerically, but not significantly, greater reductions in binge frequency, weight, and symptoms of depression were observed in those treated with chromium versus placebo, although statistical power was limited in this pilot trial. For fasting glucose, the findings suggest a dose response with larger effects in the high dose compared to moderate dose group. CONCLUSION: These initial findings support further larger trials to determine chromium's efficacy in maintaining normal glucose regulation, reducing binge eating and related psychopathology, promoting modest weight loss, and reducing symptoms of depression in individuals with BED. Studies designed to link the clinical effects of chromium with changes in underlying insulin, serotonin, and dopamine pathways may be especially informative. If efficacious, chromium supplementation may provide a useful, low-cost alternative to or augmentation strategy for selective serotonin reuptake inhibitors, which have partial efficacy in BED. ClinicalTrials.gov NCT00904306.

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.

Temporal patterns of recovery across eating disorder subtypes.

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.

Symptom profile of major depressive disorder in women with eating disorders.

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.

Use of nutritional supplements to increase the efficacy of fluoxetine in the treatment of anorexia nervosa.

OBJECTIVE: Selective serotonin reuptake inhibitor (SSRI) medication does not appear to be effective in ill, malnourished anorexia nervosa (AN) patients. However, it may be effective in preventing relapse after weight restoration. The purpose of this study was to determine whether nutritional supplements could potentiate the effects of fluoxetine in underweight AN subjects. METHOD: Twenty-six subjects with AN participated in a trial of fluoxetine. In a double-blind, placebo-controlled manner, subjects received either nutritional supplements or a nutritional placebo. The nutritional supplement included tryptophan (the precursor of serotonin), vitamins, minerals, and essential fatty acids believed to influence serotonin pathway function. RESULTS: There was no significant difference in weight gain between subjects treated with fluoxetine plus nutritional supplements versus fluoxetine plus a nutritional placebo. Moreover, there were no significant differences between groups on mean changes in anxiety or obsessive and compulsive symptoms. DISCUSSION: The results of this study suggest that supplement strategies are not a substitute for adequate nutrition and are ineffective in increasing the efficacy of fluoxetine in underweight AN subjects.