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.

Retrospective maternal report of early eating behaviours in anorexia nervosa.

This exploratory study assessed whether maternal recall of childhood feeding and eating practices differed across anorexia nervosa (AN) subtypes. Participants were 325 women from the Genetics of Anorexia Nervosa study whose mothers completed a childhood feeding and eating questionnaire. Multinomial logistic regression analyses were used to predict AN subtype from measures related to childhood eating: (i) infant feeding (breastfed, feeding schedule, age of solid food introduction), (ii) childhood picky eating (picky eating before age 1 year and between ages one and five) and (iii) infant gastrointestinal problems (vomiting and colic). Results revealed no significant differences in retrospective maternal report of childhood feeding and eating practices among AN subtypes.

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.

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.

Life beyond the eating disorder: education, relationships, and reproduction.

OBJECTIVE: We investigated the sociodemographic characteristics in women with and without lifetime eating disorders. METHOD: Participants were from a multisite international study of eating disorders (N = 2,096). Education level, relationship status, and reproductive status were examined across eating disorder subtypes and compared with a healthy control group. RESULTS: Overall, women with eating disorders were less educated than controls, and duration of illness and age of onset were associated with educational attainment. Menstrual status was associated with both relationship and reproductive status, but eating disorder subtypes did not differ significantly from each other or from healthy controls on these dimensions. DISCUSSION: Differences in educational attainment, relationships, and reproduction do exist in individuals with eating disorders and are differentially associated with various eating disorder symptoms and characteristics. These data could assist in educating patients and family members about long-term consequences of eating disorders.

The significance of repetitive hair-pulling behaviors in eating disorders.

We studied the relation between intrusive and repetitive hair pulling, the defining feature of trichotillomania, and compulsive and impulsive features in 1,453 individuals with anorexia nervosa and bulimia nervosa. We conducted a series of regression models examining the relative influence of compulsive features associated with obsessive-compulsive disorder, compulsive features associated with eating disorders, trait features related to harm avoidance, perfectionism, and novelty seeking, and self harm. A final model with a reduced sample (n = 928) examined the additional contribution of impulsive attributes. One of 20 individuals endorsed hair pulling. Evidence of a positive association with endorsement of compulsive behavior of the obsessive-compulsive spectrum emerged. Hair pulling may be more consonant with ritualistic compulsions than impulsive urges in those with eating disorders.

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.

Using Standardized Tools to Characterize Adult Day Program Populations: Implications for Future Research and Clinical Practice.

OBJECTIVES: To demonstrate the usefulness of primary data collection using clinician-rated and self-rated standardized measures to describe adult day program (ADP) populations and address programming issues such as identifying members at risk of dropping out. SETTING AND PARTICIPANTS: One ADP in London, Ontario, and 2 ADPs in Toronto, Ontario, Canada. A total of 223 community-dwelling older adults were recruited across the 3 different programs. METHODS: The interRAI Community Health or Home Care Assessment and self-rated psychosocial assessments were collected on program enrollment. Data analyses included descriptive statistics, comparison of the populations between ADPs, and multinomial regression models to assess reasons for program withdrawal. RESULTS: Mean ages across the 3 programs ranged from 78.3 to 83.8 years and the proportion of women ranged from 49.3% to 56.6%. Compared with one of the ADPs, members from 2 other ADPs exhibited higher use of mobility aids (P < .001), higher levels of cognitive impairment (P < .05), increased risk for institutionalization (P < .001), lower levels of depression (P < .01), and greater need for supervision for basic and instrumental activities of daily living (P < .01). Members assessed to be at higher risk for institutionalization and have increased medical complexity showed possible association with program withdrawal at one ADP. CONCLUSIONS AND IMPLICATIONS: The tools were useful in identifying differences in physical and psychosocial characteristics of members across the 3 ADPs. Information collected from interRAI and self-rated psychosocial assessments may be helpful in the development of individualized care plans, program services, and recommendations that target transitional care. By understanding member profiles and reasons for withdrawal, ADPs may be able to develop strategies to help members stay in the program and live in the community longer.

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.

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.

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.

Smoking in eating disorders.

OBJECTIVE: Smoking has been reported as an appetite and weight control method in eating disorders; however, few studies have explored patterns of smoking across subtypes of eating disorders. The aim of this paper was to explore the patterns and prevalence of smoking behavior in 1,524 women from two of the multisite Price Foundation Genetic studies. METHOD: Smoking behavior was assessed in 306 individuals with anorexia nervosa-restricting type (RAN), 186 with anorexia nervosa-purging type (PAN), 180 with anorexia nervosa and bulimia nervosa (ANBN), 107 with anorexia nervosa-binging type (BAN), 71 individuals with purging type-bulimia nervosa (PBN), and 674 female community controls. We compared smoking prevalence and smoking behaviors across eating disorder (ED) subtypes and in comparison to controls using the Fagerstrom Test of Nicotine Dependence (FTND). RESULTS: Overall, women with eating disorders reported higher rates of smoking and greater nicotine dependence than controls. Women with binge/purge subtypes of eating disorders reported the highest rates of smoking of all of the subtypes. Smoking in eating disorders was related to impulsive personality traits. CONCLUSIONS: Women with eating disorders appear to be at increased risk for smoking, particularly those who binge eat and/or purge and display impulsive personality characteristics. Given the high prevalence, the impact of ongoing smoking on maintenance of eating disorders symptoms is worthy of both clinical and research attention.

Temporal sequence of comorbid alcohol use disorder and anorexia nervosa.

Women with eating disorders have a significantly higher prevalence of substance use disorders than the general population. The goal of the current study was to assess the temporal pattern of comorbid anorexia nervosa (AN) and alcohol use disorder (AUD) and the impact this ordering has on symptomatology and associated features. Women were placed into one of three groups based on the presence or absence of comorbid AUD and the order of AN and AUD onset in those with both disorders: (1) AN Only, (2) AN First, and (3) AUD First. The groups were compared on psychological symptoms and personality characteristics often associated with AN, AUD, or both using general linear models. Twenty-one percent of women (n=161) with AN reported a history of AUD with 115 reporting AN onset first and 35 reporting AUD onset first. Women with binge-eating and/or purging type AN were significantly more likely to have AUD. In general, differences were found only between women with AN Only and women with AN and AUD regardless of order of emergence. Women with AN and AUD had higher impulsivity scores and higher prevalence of depression and borderline personality disorder than women with AN Only. Women with AN First scored higher on traits commonly associated with AN, whereas women with comorbid AN and AUD displayed elevations in traits more commonly associated with AUD. Results do not indicate a distinct pattern of symptomatology in comorbid AN and AUD based on the temporal sequence of the disorders.

Genetic association of recovery from eating disorders: the role of GABA receptor SNPs.

Follow-up studies of eating disorders (EDs) suggest outcomes ranging from recovery to chronic illness or death, but predictors of outcome have not been consistently identified. We tested 5151 single-nucleotide polymorphisms (SNPs) in approximately 350 candidate genes for association with recovery from ED in 1878 women. Initial analyses focused on a strictly defined discovery cohort of women who were over age 25 years, carried a lifetime diagnosis of an ED, and for whom data were available regarding the presence (n=361 ongoing symptoms in the past year, ie, 'ill') or absence (n=115 no symptoms in the past year, ie, 'recovered') of ED symptoms. An intronic SNP (rs17536211) in GABRG1 showed the strongest statistical evidence of association (p=4.63 × 10(-6), false discovery rate (FDR)=0.021, odds ratio (OR)=0.46). We replicated these findings in a more liberally defined cohort of women age 25 years or younger (n=464 ill, n=107 recovered; p=0.0336, OR=0.68; combined sample p=4.57 × 10(-6), FDR=0.0049, OR=0.55). Enrichment analyses revealed that GABA (γ-aminobutyric acid) SNPs were over-represented among SNPs associated at p<0.05 in both the discovery (Z=3.64, p=0.0003) and combined cohorts (Z=2.07, p=0.0388). In follow-up phenomic association analyses with a third independent cohort (n=154 ED cases, n=677 controls), rs17536211 was associated with trait anxiety (p=0.049), suggesting a possible mechanism through which this variant may influence ED outcome. These findings could provide new insights into the development of more effective interventions for the most treatment-resistant patients.

Refining behavioral dysregulation in borderline personality disorder using a sample of women with anorexia nervosa.

One of the primary facets of borderline personality disorder (BPD) is behavioral dysregulation, a wide array of behaviors that are difficult to control and harmful to the individual. The purpose of this study was to explore the association between BPD and a variety of dysregulated behaviors, some of which have received little empirical attention. Using a large sample of individuals diagnosed with anorexia nervosa, 41 individuals diagnosed with BPD were compared to the rest of the sample on the presence of dysregulated behaviors using logistic regression analyses. Anorexia nervosa subtypes, age, and other Cluster B personality disorders were used as covariates. Results support an association between BPD and alcohol misuse, hitting someone/breaking things, provoking fights/arguments, self-injury, overdosing, street drug use, binge-eating, impulsive spending, shoplifting/stealing, and risky sexual behaviors. Differences between dichotomous and continuous measures of BPD yielded somewhat different results. Information on co-occurring anorexia nervosa and BPD was generated.

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.

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.