Steve Crawford

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.

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.

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.

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

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.

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

Anorexia nervosa (AN) is perhaps the most lethal mental disorder, in part due to starvation-related health problems, but especially because of high suicide rates. One potential reason for high suicide rates in AN may be that those affected face pain and provocation on many fronts, which may in turn reduce their fear of pain and thereby increase risk for death by suicide. The purpose of the following studies was to explore whether repetitive exposure to painful and destructive behaviors such as vomiting, laxative use, and non-suicidal self-injury (NSSI) was a mechanism that linked AN-binge-purging (ANBP) subtype, as opposed to AN-restricting subtype (ANR), to extreme suicidal behavior. Study 1 utilized a sample of 787 individuals diagnosed with one or the other subtype of AN, and structural equation modeling results supported provocative behaviors as a mechanism linking ANBP to suicidal behavior. A second, unexpected mechanism emerged linking ANR to suicidal behavior via restricting. Study 2, which used a sample of 249 AN patients, replicated these findings, including the second mechanism linking ANR to suicide attempts. Two potential routes to suicidal behavior in AN appear to have been identified: one route through repetitive experience with provocative behaviors for ANBP, and a second for exposure to pain through the starvation of restricting in ANR.

Childhood Anxiety Associated with Low BMI in Women with Anorexia Nervosa

OBJECTIVE Extremely low body mass index (BMI) values are associated with increased risk for death and poor long-term prognosis in individuals with anorexia nervosa (AN). The present study explores childhood personality characteristics that could be associated with the ability to attain an extremely low BMI. METHODS Participants were 326 women from the Genetics of Anorexia Nervosa (GAN) Study who completed the Structured Interview for Anorexia Nervosa and Bulimic Syndromes and whose mother completed the Child Behavioral Checklist and/or Revised Dimensions of Temperament Survey. RESULTS Children who were described as having greater fear or anxiety by their mothers attained lower BMIs during AN (p < 0.02). Path analysis in the GAN and a validation sample, Price Foundation Anorexia Nervosa Trios Study, confirmed the relation between early childhood anxiety, caloric restriction, qualitative food item restriction, excessive exercise, and low BMI. Path analysis also confirmed a relation between childhood anxiety and caloric restriction, which mediated the relation between childhood anxiety and low BMI in the GAN sample only. CONCLUSION Fearful or anxious behavior as a child was associated with the attainment of low BMI in AN and childhood anxiety was associated with caloric restriction. Measures of anxiety and factors associated with anxiety-proneness in childhood may index children at risk for restrictive behaviors and extremely low BMIs in AN.

Posttraumatic Stress Disorder in Anorexia Nervosa

Objectives: Comorbidity among eating disorders, traumatic events, and posttraumatic stress disorder (PTSD) has been reported in several studies. The main objectives of this study were to describe the nature of traumatic events experienced and to explore the relationship between PTSD and anorexia nervosa (AN) in a sample of women. Methods: Eight hundred twenty-four participants from the National Institutes of Health-funded Genetics of Anorexia Nervosa Collaborative Study were assessed for eating disorders, PTSD, and personality characteristics. Results: From a final sample of 753 women with AN, 13.7% (n = 103) met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for PTSD. The sample mean age was 29.5 (standard deviation = 11.1) years. In pairwise comparisons across AN subtypes, the odds of having a PTSD diagnosis were significantly lower in individuals with restricting AN than individuals with purging AN without binge eating (odds ratio = 0.49, 95% confidence interval = 0.30-0.80). Most participants with PTSD reported the first traumatic event before the onset of AN (64.1%, n = 66). The most common traumatic events reported by those with a PTSD diagnosis were sexually related traumas during childhood (40.8%) and during adulthood (35.0%). Conclusions: AN and PTSD do co-occur, and traumatic events tend to occur before the onset of AN. Clinically, these results underscore the importance of assessing trauma history and PTSD in individuals with AN and raise the question of whether specific modifications or augmentations to standard treatment for AN should be considered in a subgroup to address PTSD-related psychopathology.AN = anorexia nervosa; ANBN = lifetime diagnosis of both anorexia and bulimia nervosa; BAN = anorexia nervosa with binge, with or without purging; BN = bulimia nervosa; BMI = body mass index; DSM-IV = Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition; HPA = hypothalamic-pituitary-adrenal; PAN = purging anorexia nervosa without binge eating; PTSD = posttraumatic stress disorder; RAN = restricting anorexia nervosa; Y-BOCS = Yale-Brown Obsessive Compulsive Scale; YBC-EDS = Yale-Brown-Cornell Eating Disorder Scale.

Understanding the Association of Impulsivity, Obsessions, and Compulsions with Binge Eating and Purging Behaviours in Anorexia Nervosa

OBJECTIVE To further refine our understanding of impulsivity, obsessions, and compulsions in anorexia nervosa (AN) by isolating which behaviours--binge eating, purging, or both--are associated with these features. METHODS We conducted regression analyses with binge eating, purging, and the interaction of binge eating with purging as individual predictors of scores for impulsivity, obsessions, and compulsions in two samples of women with AN (n = 1373). RESULTS Purging, but not binge eating, was associated with higher scores on impulsivity, obsessions, and compulsions. Purging was also associated with worst eating rituals and with worst eating preoccupations. CONCLUSION Our results suggest that purging, compared with binge eating, may be a stronger correlate of impulsivity, obsessions, and compulsions in AN.

An examination of early childhood perfectionism across anorexia nervosa subtypes.

OBJECTIVE To examine childhood perfectionism in anorexia nervosa (AN) restricting (RAN), purging (PAN), and binge eating with or without purging (BAN) subtypes. METHOD The EATATE, a retrospective assessment of childhood perfectionism, and the eating disorder inventory (EDI-2) were administered to 728 AN participants. RESULTS EATATE responses revealed general childhood perfectionism, 22.3% of 333 with RAN, 29.2% of 220 with PAN, and 24.8% of 116 with BAN; school work perfectionism, 31.2% with RAN, 30.4% with PAN, and 24.8% with BAN; childhood order and symmetry, 18.7% with RAN, 21.7% with PAN, and 17.8% with BAN; and global childhood rigidity, 42.6% with RAN, 48.3% with PAN and 48.1% with BAN. Perfectionism preceded the onset of AN in all subtypes. Significant associations between EDI-2 drive for thinness and body dissatisfaction were present with four EATATE subscales. DISCUSSION Global childhood rigidity was the predominate feature that preceded all AN subtypes. This may be a risk factor for AN.

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.