Elasticity in portion selection is predicted by severity of anorexia and food type in adolescents.

The size of portions that people select is an indicator of underlying mechanisms controlling food intake. Fears of eating excessive portions drive down the sizes of portions patients with anorexia nervosa (AN) can tolerate eating significantly below those of healthy controls (HC) (Kissileff et al., 2016). To determine whether patients with AN will also reduce the sizes of typical or ideal portions below those of controls, ANOVA was used to compare maximum tolerable, typical, and ideal portions of four foods (potatoes, rice, pizza, and M&M's) in the same group of 24 adolescent AN patients and 10 healthy adolescent controls (HC), on which only the maximal portion data were previously reported. Typical and ideal portion sizes did not differ on any food for AN, but for HC, typical portions sizes (kcals) became larger than ideal as the energy density of the food increased, and were significant for the most energy dense food. Ideal portions of low energy dense foods were the same for AN as for in HC. There was a significant 3-way (group × food × portion type) interaction, such that HC selected larger maximum than typical portions only for pizza. We therefore proposed that individuals of certain groups, depending on the food, can be flexible in the amounts of food chosen to be eaten. We call this difference between maximum-tolerable, and typical portion sizes selected "elasticity." Elasticity was significantly smaller for AN patients compared to HC for pizza and was significantly inversely correlated with severity of illness. This index could be useful for clinical assessment of AN patients, and those with eating problems such as in obesity and bulimia nervosa and tracking their response to treatment.

Computerized measurement of anticipated anxiety from eating increasing portions of food in adolescents with and without anorexia nervosa: Pilot studies.

Dieting and excessive fear of eating coexist in vulnerable individuals, which may progress to anorexia nervosa [AN], but there is no objective measure of this fear. Therefore, we adapted a computer program that was previously developed to measure the satiating effects of foods in order to explore the potential of food to induce anxiety and fear of eating in adolescent girls. Twenty four adolescents (AN) and ten healthy controls without eating disorders rated pictures of different types of foods in varying sized portions as too large or too small and rated the expected anxiety of five different portions (20-320 kcal). Two low energy dense (potatoes and rice) and two high energy dense (pizza and M&Ms) foods were used. The regression coefficient of line lengths (0-100 mm) marked from "No anxiety" to "this would give me a panic attack", regressed from portions shown, was the measure of "expected anxiety" for a given food. The maximum tolerated portion size [kcal] (MTPS), computed by method of constant stimulus from portions shown, was significantly smaller for high energy dense foods, whereas the expected anxiety response was greater, for all foods, for patients compared to controls. For both groups, expected anxiety responses were steeper, and maximum tolerated portion sizes were larger, for low, than high, energy dense foods. Both maximum tolerated portion size and expected anxiety response were significantly predicted by severity of illness for the patients. Those who had larger maximum tolerated portion sizes had smaller anticipated anxiety to increasing portion sizes. Visual size had a greater influence than energy content for these responses. This method could be used to quantify the anxiety inducing potential of foods and for studies with neuro-imaging and phenotypic clarifications.

Dysregulation of soluble epoxide hydrolase and lipidomic profiles in anorexia nervosa.

Individuals with anorexia nervosa (AN) restrict eating and become emaciated. They tend to have an aversion to foods rich in fat. Because epoxide hydrolase 2 (EPHX2) was identified as a novel AN susceptibility gene, and because its protein product, soluble epoxide hydrolase (sEH), converts bioactive epoxides of polyunsaturated fatty acid (PUFA) to the corresponding diols, lipidomic and metabolomic targets of EPHX2 were assessed to evaluate the biological functions of EPHX2 and their role in AN. Epoxide substrates of sEH and associated oxylipins were measured in ill AN, recovered AN and gender- and race-matched controls. PUFA and oxylipin markers were tested as potential biomarkers for AN. Oxylipin ratios were calculated as proxy markers of in vivo sEH activity. Several free- and total PUFAs were associated with AN diagnosis and with AN recovery. AN displayed elevated n-3 PUFAs and may differ from controls in PUFA elongation and desaturation processes. Cytochrome P450 pathway oxylipins from arachidonic acid, linoleic acid, alpha-linolenic acid and docosahexaenoic acid PUFAs are associated with AN diagnosis. The diol:epoxide ratios suggest the sEH activity is higher in AN compared with controls. Multivariate analysis illustrates normalization of lipidomic profiles in recovered ANs. EPHX2 influences AN risk through in vivo interaction with dietary PUFAs. PUFA composition and concentrations as well as sEH activity may contribute to the pathogenesis and prognosis of AN. Our data support the involvement of EPHX2-associated lipidomic and oxylipin dysregulations in AN, and reveal their potential as biomarkers to assess responsiveness to future intervention or treatment.

Evidence for the role of EPHX2 gene variants in anorexia nervosa.

Anorexia nervosa (AN) and related eating disorders are complex, multifactorial neuropsychiatric conditions with likely rare and common genetic and environmental determinants. To identify genetic variants associated with AN, we pursued a series of sequencing and genotyping studies focusing on the coding regions and upstream sequence of 152 candidate genes in a total of 1205 AN cases and 1948 controls. We identified individual variant associations in the Estrogen Receptor-ß (ESR2) gene, as well as a set of rare and common variants in the Epoxide Hydrolase 2 (EPHX2) gene, in an initial sequencing study of 261 early-onset severe AN cases and 73 controls (P=0.0004). The association of EPHX2 variants was further delineated in: (1) a pooling-based replication study involving an additional 500 AN patients and 500 controls (replication set P=0.00000016); (2) single-locus studies in a cohort of 386 previously genotyped broadly defined AN cases and 295 female population controls from the Bogalusa Heart Study (BHS) and a cohort of 58 individuals with self-reported eating disturbances and 851 controls (combined smallest single locus P<0.01). As EPHX2 is known to influence cholesterol metabolism, and AN is often associated with elevated cholesterol levels, we also investigated the association of EPHX2 variants and longitudinal body mass index (BMI) and cholesterol in BHS female and male subjects (N=229) and found evidence for a modifying effect of a subset of variants on the relationship between cholesterol and BMI (P<0.01). These findings suggest a novel association of gene variants within EPHX2 to susceptibility to AN and provide a foundation for future study of this important yet poorly understood condition.

A 1-year follow-up of a multi-center treatment trial of adults with anorexia nervosa.

OBJECTIVE: To examine maintenance of recovery following treatment in an adult anorexia nervosa (AN) population. METHOD: One year follow-up of a randomized clinical trial with 122 participants treated with: cognitive behavioral therapy (CBT), drug therapy (fluoxetine), or a combination (CBT+fluoxetine) for 12 months. Participants were assessed at baseline, end of treatment, and follow-up. The primary outcomes were weight and the global scores from the Eating Disorder Examination (EDE) separately and combined. RESULTS: Fifty-two participants completed the follow-up. Mean weight increased from end of treatment to follow-up. Seventy-five percent (75%) of those weight recovered at end of treatment maintained this recovery at follow-up. Recovery of eating disorder psychopathology was stable from end of treatment to follow-up, with 40% of participants with a global EDE score within normal range. Using the most stringent criteria for recovery, only 21% of the completer sample was recovered. DISCUSSION: The findings suggest that while adults with AN improve with treatment and maintain these improvements during follow-up, the majority is not recovered. Additionally, further research is needed to understand barriers to treatment and assessment completion.

Is season of birth related to disordered eating and personality in women with eating disorders?

We assessed the relation between season of birth and eating disorder symptoms and personality characteristics in a sample of 880 women with eating disorders and 580 controls from two Price Foundation Studies. Eating disorder symptoms were assessed using the Structured Interview of Anorexic and Bulimic Disorders and the Structured Clinical Interview for DSM-IV. Personality traits were assessed using the Temperament and Character Inventory and the Frost Multidimensional Perfectionism Scale. Date of birth was obtained from a sociodemographic questionnaire. No significant differences were observed 1) in season of birth across eating disorder subtypes and controls; nor 2) for any clinical or personality variables and season of birth. We found no evidence of season of birth variation in eating disorders symptoms or personality traits. Contributing to previous conflicting findings, the present results do not support a season of birth hypothesis for eating disorders.

Anorexia nervosa trios: behavioral profiles of individuals with anorexia nervosa and their parents.

BACKGROUND: Anorexia nervosa (AN) is associated with behavioral traits that predate the onset of AN and persist after recovery. We identified patterns of behavioral traits in AN trios (proband plus two biological parents). METHOD: A total of 433 complete trios were collected in the Price Foundation Genetic Study of AN using standardized instruments for eating disorder (ED) symptoms, anxiety, perfectionism, and temperament. We used latent profile analysis and ANOVA to identify and validate patterns of behavioral traits. RESULTS: We distinguished three classes with medium to large effect sizes by mothers' and probands' drive for thinness, body dissatisfaction, perfectionism, neuroticism, trait anxiety, and harm avoidance. Fathers did not differ significantly across classes. Classes were distinguished by degree of symptomatology rather than qualitative differences. Class 1 (approximately 33%) comprised low symptom probands and mothers with scores in the healthy range. Class 2 ( approximately 43%) included probands with marked elevations in drive for thinness, body dissatisfaction, neuroticism, trait anxiety, and harm avoidance and mothers with mild anxious/perfectionistic traits. Class 3 (approximately 24%) included probands and mothers with elevations on ED and anxious/perfectionistic traits. Mother-daughter symptom severity was related in classes 1 and 3 only. Trio profiles did not differ significantly by proband clinical status or subtype. CONCLUSIONS: A key finding is the importance of mother and daughter traits in the identification of temperament and personality patterns in families affected by AN. Mother-daughter pairs with severe ED and anxious/perfectionistic traits may represent a more homogeneous and familial variant of AN that could be of value in genetic studies.

Candidate genes for anorexia nervosa in the 1p33-36 linkage region: serotonin 1D and delta opioid receptor loci exhibit significant association to anorexia nervosa.

Serotonergic and opioidergic neurotransmitter system alterations have been observed in people with eating disorders; the genes for the serotonin 1D receptor (HTR1D) and the opioid delta receptor (OPRD1) are found on chr1p36.3-34.3, a region identified by our group in a linkage analysis of anorexia nervosa (AN). These candidate genes were evaluated for sequence variation and for linkage and association of this sequence variation to AN in family and case : control data sets. Resequencing of the HTR1D locus and a portion of the OPRD1 locus identified novel SNPs and confirmed existing SNPs. Genotype assay development and genotyping of nine SNPs (four at HTR1D and five at OPRD1) was performed on 191 unrelated individuals fulfilling DSM-IV criteria (w/o amenorrhea criterion) for AN, 442 relatives of AN probands and 98 psychiatrically screened controls. Linkage analysis of these candidate gene SNPs with 33 microsatellite markers in families including relative pairs concordantly affected with restricting AN (N=37) substantially increased the evidence for linkage of this region to restricting AN to an NPL score of 3.91. Statistically significant genotypic, allelic, and haplotypic association to AN in the case : control design was observed at HTR1D and OPRD1 with effect sizes for individual SNPs of 2.63 (95% CI=1.21-5.75) for HTR1D and 1.61 (95% CI=1.11-2.44) for OPRD1. Using genotype data on parents and AN probands, three SNPs at HTR1D were found to exhibit significant transmission disequilibrium (P&<0.05). The combined statistical genetic evidence suggests that HTR1D and OPRD1 or linked genes may be involved in the etiology of AN.

Evidence for a susceptibility gene for anorexia nervosa on chromosome 1.

Eating disorders, such as anorexia nervosa (AN), have a significant genetic component. In the current study, a genomewide linkage analysis of 192 families with at least one affected relative pair with AN and related eating disorders, including bulimia nervosa, was performed, resulting in only modest evidence for linkage, with the highest nonparametric linkage (NPL) score, 1.80, at marker D4S2367 on chromosome 4. Since the reduction of sample heterogeneity would increase power to detect linkage, we performed linkage analysis in a subset (n=37) of families in which at least two affected relatives had diagnoses of restricting AN, a clinically defined subtype of AN characterized by severe limitation of food intake without the presence of binge-eating or purging behavior. When we limited the linkage analysis to this clinically more homogeneous subgroup, the highest multipoint NPL score observed was 3.03, at marker D1S3721 on chromosome 1p. The genotyping of additional markers in this region led to a peak multipoint NPL score of 3.45, thereby providing suggestive evidence for the presence of an AN-susceptibility locus on chromosome 1p.

Differences in DSM-III-R and DSM-IV diagnoses in eating disorder patients.

Two hundred eighty-eight eating disorder patients were administered the DSM-III-R Structured Clinical Interview (SCID) and the DSM-IV SCID for axis I and II. Concordance between DSM-III-R and DSM-IV was excellent for the axis I affective and anxiety disorders, bulimia nervosa, and substance abuse/dependence. It was also excellent for axis II paranoid, schizoid, borderline, and antisocial personality disorders. Agreement between the two nosological systems was lower for alcohol abuse/dependence with a kappa of.63. Kappas were also poor for the following personality disorders: schizotypal (.44), histrionic (.29), dependent (.54), obsessive-compulsive (.62) and not otherwise specified (.63). There was a substantial difference in the diagnosis of anorexia nervosa between DSM-III-R and DSM-IV. Fourteen patients were diagnosed with anorexia nervosa, binge/purge type, using DSM-IV criteria, while only six received the diagnoses of anorexia nervosa and bulimia nervosa using DSM-III-R criteria. Kappa was.49 and the percent agreement was 79%. While there are considerable areas of overlap in DSM-IV and DSM-III-R, there are also areas of substantial differences. Clinicians and researchers must be very cautious when attempting to compare data from the different nosologies.

Neurocognitive evidence favors "top down" over "bottom up" mechanisms in the pathogenesis of body size distortions in anorexia nervosa.

Perceptually-based disturbances in body image, or body size distortions, have been posited to occur in anorexia nervosa (AN). Perception does not result from a simple flow of sensory information from periphery to cortex ("bottom-up" processing), but involves the selection of inputs most likely to be relevant in light of an individual's experience and expectations ("top-down" processing). Most investigations of body size distortion in AN have used procedures likely to engage top-down processing, raising the possibility that attitudinal disturbances may play a role. To our knowledge, there have been no studies that assess the presence, in AN, of neurocognitive deficits associated with neurologically based disturbances in body schema. Such deficits, if found, could provide evidence of body image distortion unlikely to result from top-down processing. We tested 20 inpatients with AN on measures of proprioception, finger identification, right/left orientation, general cognition and eating disorders symptomatology, both before and after treatment. Matched normal controls were tested on the same measures over the same time intervals. Significant differences between the two groups occurred only prior to treatment, and only on those measures which involved executive, in addition to more body-schema-specific functions. This suggests that patients with AN do not have enduring deficits in the domain of body-schema, but may have subtle cognitive dysfunction, in the acute state, which is not specific to, but can interact with processing of body-schema-related information. This, in turn, suggests that their body image distortion may not be secondary to bottom-up perceptual disturbances.

An eating disorder curriculum for primary care providers.

OBJECTIVE: Primary care providers frequently lack adequate training in treating eating disorders. This study examined the effectiveness of an eating disorder curriculum designed to address the lack of knowledge among primary care providers. METHOD: Medical social workers completed four intensive training sessions, each lasting 75 min. Participants completed questionnaires assessing eating disorder knowledge, perceived ability to treat eating disorders, and practice behaviors, before and after training as well as at 6-month follow-up. RESULTS: The eating disorder curriculum resulted in a significant increase in eating disorder knowledge and a moderate improvement in practice behaviors such as screening new patients for an eating disorder. Training did not significantly change providers' perceived ability to intervene. DISCUSSION: The results of this pilot study suggest that brief intensive training can increase providers' knowledge and change their routine clinical practices, resulting in increased rates of detection and intervention in the primary care setting.

Subtyping binge eating-disordered women along dieting and negative affect dimensions.

OBJECTIVE: Because etiologic and maintenance models of binge eating center around dieting and affect regulation, this study tested whether binge eating-disordered (BED) individuals could be subtyped along dieting and negative affect dimensions and whether subtypes differed in eating pathology, social functioning, psychiatric comorbidity, and response to treatment. METHOD: Three independent samples of interviewer-diagnosed BED women (N = 218) were subtyped along dieting and negative affect dimensions using cluster analysis and compared on the outcomes of interest. RESULTS: Cluster analyses replicated across the three independent samples and revealed a dietary subtype (63%) and a dietary-depressive subtype (37%). The latter subtype reported greater eating and weight obsessions, social maladjustment, higher lifetime rates of mood, anxiety, and personality disorders, and poorer response to treatment than did the dietary subtype. DISCUSSION: Results suggest that moderate dieting is a central feature of BED and that affective disturbances occur in only a subset of cases. However, the confluence of dieting and negative affect signals a more severe variant of the disorder marked by elevated psychopathology, impaired social functioning, and a poorer treatment response.

Changing patterns of hospitalization in eating disorder patients.

OBJECTIVE: This study investigated the changing patterns of hospitalization of eating disorder patients over the past 15 years. METHOD: The records of 1,185 eating disorder patients between 1984 and 1998 were examined on several variables. RESULTS: Over the 15 years, the number of first admissions increased from 20 to 182. There was a concomitant decrease in length of stay from 149.5 days in 1984 to 23.7 days in 1998. Readmissions increased markedly from 0% during the first year to 27% of total admissions in 1998. The discharge weight of anorectic patients significantly decreased from a body mass index (BMI) of 19.3 in 1984 to 17.7 in 1998. These changes were particularly salient in the past 3 years, concurrent with a dramatic rise in managed care cases. CONCLUSIONS: Over the past 15 years, eating disorder hospital treatment has metamorphozed from long-term treatment of a disorder to stabilization of acute episodes. For some patients, this change has been deleterious and not cost effective.

Developing an eating disorder curriculum for primary care providers.

As the number of eating disorder cases rises, primary care providers are increasingly called upon to diagnose and treat eating disorder patients. Unfortunately, few primary care providers have the necessary experience and training to adequately treat these patients. The Eating Disorder Curriculum for Primary Care Providers has been specifically designed to addresses this lack of training and improve the rate of early detection. This is accomplished through basic didactic sessions and individualized instruction on the specifics of manualized treatment in the primary care setting.

Perfectionism in anorexia nervosa: variation by clinical subtype, obsessionality, and pathological eating behavior.

OBJECTIVE: The purpose of this study was to examine the role of perfectionism as a phenotypic trait in anorexia nervosa and its relevance across clinical subtypes of this illness. METHOD: The Multidimensional Perfectionism Scale and the perfectionism subscale of the Eating Disorder Inventory were administered to 322 women with a history of anorexia nervosa who were participating in an international, multicenter genetic study of anorexia nervosa. All participants were additionally interviewed with the Yale-Brown Obsessive Compulsive Scale and the Yale-Brown-Cornell Eating Disorder Scale. Mean differences on dependent measures among women with anorexia nervosa and comparison subjects were examined by using generalized estimating equations. RESULTS: Persons who had had anorexia nervosa had significantly higher total scores on the Multidimensional Perfectionism Scale than did the healthy comparison subjects. In addition, scores of the anorexia subjects on the Eating Disorder Inventory-2 perfectionism subscale exceeded Eating Disorder Inventory-2 normative data. For the anorexia nervosa participants, the total score on the Multidimensional Perfectionism Scale and the Eating Disorder Inventory-2 perfectionism subscale score were highly correlated. Total score on the Multidimensional Perfectionism Scale was also significantly related to the total score and the motivation-for-change subscale score of the Yale-Brown-Cornell Eating Disorder Scale. CONCLUSIONS: These data show that perfectionism is a robust, discriminating characteristic of anorexia nervosa. Perfectionism is likely to be one of a cluster of phenotypic trait variables associated with a genetic diathesis for anorexia nervosa.

Comparison of the yale-brown-cornell eating disorders scale in recovered eating disorder patients, restrained dieters, and nondieting controls.

OBJECTIVE: Yale-Brown-Cornell Eating Disorder Scale (YBC-EDS) scores were assessed in recovered eating disorder patients, restrained dieters, and unrestrained nondieters. METHOD: YBC-EDS interviews were conducted with 53 recovered eating disorder patients who had no symptoms within at least 6 months, 29 restrained dieters, and 36 unrestrained controls. RESULTS: Unrestrained control subjects had no typical eating-disordered preoccupations or rituals. The majority (62%) of restrained dieters did have current eating-disordered preoccupations but only 5 had current eating-disordered rituals. Most recovered eating disorder subjects had no current eating-disordered preoccupations (66%) and 76% had no current eating-disordered rituals. Unrestrained eating controls had significantly lower Preoccupation, Total, and Motivation to Change scores on the YBC-EDS than the other groups and significantly lower Ritual scores than the recovered eating disorder group. There were no significant differences between the restrained dieters and the recovered eating disorder group. DISCUSSION: Recovered eating disorder patients who no longer meet any of the DSM-IV criteria for an eating disorder are similar in severity of eating concern to normal weight restrained eating dieters. Both of these groups have more eating and weight concerns as compared with the unrestrained eating, nondieting controls. The YBC-EDS effectively distinguishes the healthy eating controls from restrained eating dieters and recovered eating disorder patients.

Temperament and character in women with anorexia nervosa.

The present study examined temperament differences among anorexia nervosa (AN) subtypes and community controls, as well as the effect of body weight on personality traits in women with AN. Temperament and Character Inventory (TCI) scores were compared between 146 women with restrictor-type AN (RAN), 117 women with purging-type AN (PAN), 60 women with binge/purge-type AN (BAN), and 827 community control women (CW) obtained from an archival normative database. Women with AN scored significantly higher on harm avoidance and significantly lower on cooperativeness than CW. Subtype analyses revealed that women with RAN and PAN reported the lowest novelty seeking, RAN women the highest persistence and self-directedness, and PAN women the highest harm avoidance. Body mass index had a nominal effect on subgroup differences, suggesting that personality disturbances are independent of body weight. Findings suggest that certain facets of temperament differ markedly between women with AN, regardless of diagnostic subtype, and controls. More subtle temperament and character differences that were independent of body weight emerged that distinguish among subtypes of AN.

Outcome predictors for the cognitive behavior treatment of bulimia nervosa: data from a multisite study.

OBJECTIVE: The aim of this study was to discover clinically useful predictors of attrition and outcome in the treatment of bulimia nervosa with cognitive behavior therapy. METHOD: Pretreatment, course of treatment, and outcome data were gathered on 194 women meeting the DSM-III-R criteria for bulimia nervosa who were treated with 18 sessions of manual-based cognitive behavior therapy in a three-site study. Differences between dropouts and nondropouts and between recovered and nonrecovered participants were first examined descriptively, and signal detection analyses were then used to determine clinically significant cutoff points predicting attrition and abstinence. RESULTS: The dropouts were characterized by more severe bulimic cognitions and greater impulsivity, but it was not possible to identify clinically useful predictors. The participants with treatment failures were characterized by poor social adjustment and a lower body mass index, presumably indicating greater dietary restriction. However, early progress in therapy best predicted outcome. Signal detection analyses revealed that poor outcome was predicted by a reduction in purging of less than 70% by treatment session 6, allowing identification of a substantial proportion of prospective failures. CONCLUSIONS: A cutoff point based on reduction of purging by session 6 usefully differentiates patients who will and will not respond to cognitive behavior therapy for bulimia nervosa, potentially allowing early use of a second therapy.

Establishing guidelines for pharmacotherapy trials in bulimia nervosa and anorexia nervosa.

OBJECTIVE: This paper addresses the lack of a standard protocol for pharmacotherapy trials for patients with bulimia nervosa (BN) and anorexia nervosa (AN). METHOD: Twenty-two surveys were sent to established researchers in the field of eating disorders to elicit their opinions regarding medication trials, including baseline laboratory tests, the optimal length/frequency of medication management sessions, and the information that should or should not be included in these sessions. RESULTS: Sixteen of 22 researchers completed and returned the survey. Their answers are the basis of the data presented. DISCUSSION: We propose a battery of screening laboratory tests for both conditions. We suggest 30-45-min initial medication management sessions in both AN and BN trials with 15-min follow-ups to be held weekly for AN subjects, and weekly for 2 weeks, then biweekly for 2 weeks, then monthly, for BN subjects. We also recommend that published trials should include explicit details of medication management.