Therapist adherence to family-based treatment for adolescents with anorexia nervosa: A multi-site exploratory study.

OBJECTIVE: This exploratory study is the first to examine family-based treatment (FBT) adherence and association to treatment outcome in the context of a large-scale, multi-centre study for the treatment of adolescents with anorexia nervosa. METHOD: One hundred and ninety recorded FBT sessions from 68 adolescents with anorexia nervosa and their families were recruited across multiple sites (N = 6). Each site provided 1-4 tapes per family over four treatment time points, and each was independently rated for therapist adherence. RESULTS: There were differences in adherence scores within and between sites. ANOVA produced a main effect for site, F(5, 46) = 8.6, p < .001, and phase, F(3, 42) = 12.7, p < .001, with adherence decreasing in later phases. Adherence was not associated to end of treatment percent ideal body weight after controlling for baseline percent ideal body weight (r = .088, p = .48). CONCLUSIONS: Results suggest that FBT can be delivered with adherence in phase one of treatment. Adherence was not associated with treatment outcome as determined using percent ideal body weight.

A randomized controlled trial of group cognitive remediation therapy for anorexia nervosa: Effects on set-shifting tasks for inpatient adults and adolescents.

OBJECTIVE: The aim of this randomized controlled trial with a parallel design was to evaluate the effect of brief, cognitive remediation therapy (CRT) for anorexia nervosa (AN) on set-shifting. METHOD: Two hundred seventy-five inpatient adults and adolescents with AN (mean age = 23.1; SD = 12.7) were randomly assigned (using simple randomization procedures) to either a CRT or control condition. All participants received treatment as usual; however, the CRT condition completed five CRT group sessions in lieu of other group therapies provided on the unit. Set-shifting abilities were evaluated by: (a) neuropsychological measures and (b) experimental cognitive behavior therapy thought records. Blinding of group assignment occurred during baseline assessment and ended following group commencement. RESULTS: Data from 135 CRT and 140 control condition participants were analyzed. On all neuropsychological measures, results revealed no between group condition effects, but did show statistically significant time effects, with medium to large effect sizes. Thought record analysis revealed a significant condition by age interaction effect where adults in the CRT condition generated significantly more alternative thoughts and had stronger believability of alternative thoughts than children, a trend that was not found in the control condition. This yielded moderate to large effect sizes of.0.56 and 0.72, respectively. DISCUSSION: Based on traditional neuropsychological measures, these findings do not suggest a differential effect of CRT for AN in the format applied. However, results suggest that CRT may have some increased beneficial cognitive effect for adults, as compared to children, based on thought record analysis.

An investigation of indirect effects of personality features on anorexia nervosa severity through interoceptive dysfunction in individuals with lifetime anorexia nervosa diagnoses.

OBJECTIVE: This study examined a hypothesized pathway by which interoceptive dysfunction accounted for associations between personality features (harm avoidance, self-directedness, and perfectionism) and anorexia nervosa (AN) severity (indicated by drive for thinness, eating disorder-related preoccupations and rituals, and body mass index). METHOD: The study sample (n = 270, mean age = 28.47, 95.2% female, 98% White/Caucasian) consisted of probands and biological relatives who met DSM-IV criteria for lifetime diagnoses of AN (omitting criterion D, amenorrhea) drawn from the Price Foundation Anorexia Nervosa Affected Relative Pairs Study (AN-ARP). Participants completed measures assessing personality, interoceptive dysfunction, and eating pathology. RESULTS: Associations between personality features of low self-directedness and high perfectionism and indicators of AN severity (drive for thinness and eating disorder-related preoccupations and rituals) were significant, as were the hypothesized indirect pathways through interoceptive dysfunction. Neither harm avoidance nor body mass index was significantly related to other study variables, and the proposed indirect pathways involving these variables were not significant. DISCUSSION: Findings suggest that certain personality features may relate to AN severity, in part, through their associations with interoceptive dysfunction. Future research should examine prospective associations and the value of interventions targeting interoceptive dysfunction for interrupting the link between personality and AN severity.

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.

Are parental self-efficacy and family flexibility mediators of treatment for anorexia nervosa?

OBJECTIVE: Family-based treatment (FBT) for adolescent anorexia nervosa (AN) promotes faster weight restoration when compared to other treatments. However, the mechanisms through which this occurs are not clarified. This study explored the trajectories of parental self-efficacy and perceived family flexibility during FBT and systemic family therapy (SyFT). We also explored whether parental self-efficacy mediates the effects of treatment on weight gain early in treatment. METHOD: 158 adolescents (12-18 years old; 89% girls) and their parents were randomized to FBT or SyFT. Parental self-efficacy as well as adolescents' and parental perceptions of the family's flexibility were collected at baseline and at sessions 2, 4, 6, and 8. RESULTS: Over time, only parents in FBT reported significantly greater self-efficacy. The change in maternal self-efficacy over the first 8 weeks of treatment was a significant mediator of session 10 weight gain. There were no significant group differences in perceived flexibility by session 8. DISCUSSION: Both parents in FBT and mothers in SyFT understand early the need to change their family's rules and roles. However, the specific strategies of FBT appear to mediate early weight gain in AN.

Does family-based treatment reduce the need for hospitalization in adolescent anorexia nervosa?

OBJECTIVE: We examined the timing and number of days of hospitalization during the course of treatment, hospitalization effects on outcome, and predictors and moderators of the use of hospitalization in adolescents with anorexia nervosa (AN). METHOD: Data used in this study were collected from 158 adolescents (ages 12 to 18 years of age) who met DSM-IVTR criteria for AN (exclusive of the amenorrhea criteria) randomized to receive either Family Based Treatment (FBT) or Systemic Family Therapy (SyFT) in a 7 site study. RESULTS: The trajectory of hospital day use is similar in the first 5 weeks irrespective of treatment allocation. However, days of hospitalization continued to increase throughout SyFT but leveled off in FBT after ∼5 weeks of treatment. Early hospitalization was a negative predictor for improvements in percent weight change for both treatment groups (t(1)=2.6, p = 0.011). Co-morbid psychopathology predicted early hospital use in both treatments. Higher levels of eating related obsessions and depression moderated hospitalization rates suggesting that FBT reduces early hospitalization rates compared to SyFT for these subgroups. DISCUSSION: These data support and extend findings from previous studies by identifying patterns of hospital use, and predictors and moderators of treatment effect for early hospitalization use in adolescent AN. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:891-894).

Primary amenorrhea in anorexia nervosa: impact on characteristic masculine and feminine traits.

Animal studies indicate that gonadal hormones at puberty have an effect on the development of masculine and feminine traits. However, it is unknown whether similar processes occur in humans. We examined whether women with anorexia nervosa (AN), who often experience primary amenorrhea, exhibit attenuated feminization in their psychological characteristics in adulthood due to the decrease/absence of gonadal hormones at puberty. Women with AN were compared on a number of psychological characteristics using general linear models on the basis of the presence/absence of primary amenorrhea. Although women with primary amenorrhea exhibited lower anxiety scores than those without primary amenorrhea, in general, results did not provide evidence of attenuated feminization in women with AN with primary amenorrhea. Future research should utilize novel techniques and direct hormone measurement to explore the effects of pubertal gonadal hormones on masculine and feminine traits.

Challenges in conducting a multi-site randomized clinical trial comparing treatments for adolescent anorexia nervosa.

OBJECTIVE: To describe obstacles in the implementation of a controlled treatment trial of adolescent anorexia nervosa (AN). METHOD: The original aim was to enter 240 participants with AN to one of four cells: Behavioral family therapy (BFT) plus fluoxetine; BFT plus placebo; systems family therapy (SFT) plus fluoxetine; SFT plus placebo. RESULTS: Recruitment was delayed pending a satisfactory resolution concerning participant safety. After 6 months of recruitment it became clear that the medication was associated with poor recruitment leading to a study redesign resulting in a comparison of two types of family therapy with a projected sample size of 160. One site was unable to recruit and was replaced. DISCUSSION: Problems with the delineation of safety procedures, recruitment, re-design of the study, and replacement of a site, were the main elements resulting in a 1-year delay. Suggestions are made for overcoming such problems in future AN trials.

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.

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors.

BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.

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.

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.

Exploring Differences in the Role of Hospitalization on Weight Gain Based on Treatment Type From Randomized Clinical Trials for Adolescent Anorexia Nervosa.

Background: This study explores the impact of weight gain during medical stabilization hospitalization on weight outcomes between three outpatient treatments for adolescent anorexia nervosa (AN): Adolescent Focused Therapy (AFT), Systemic Family Therapy (SyFT), and Family Based Treatment (FBT). Methods: A secondary analysis of weight gain data (N = 215) of adolescents (12-18 years) meeting DSM-IV criteria for AN (exclusive of amenorrhea criteria) who participated in two randomized clinical trials (RCTs) was conducted. Main outcomes examined were changes in weight restoration (≥95% expected body weight or EBW) and differences in weight change attributable to hospital weight gain. Results: Weight gain resulting from hospitalizations did not substantially change weight recovery rates. Hospital weight gain contributed most to overall treatment weight gain in AFT compared to FBT and SyFT. Conclusion: Brief medical stabilization weight gain does not contribute substantially to weight recovery in adolescents with AN who participated in RCTs.