Allan S. Kaplan

The slippery slope: prediction of successful weight maintenance in anorexia nervosa

BACKGROUND Previous research has found that many patients with anorexia nervosa (AN) are unable to maintain normal weight after weight restoration. The objective of this study was to identify variables that predicted successful weight maintenance among weight-restored AN patients. METHOD Ninety-three patients with AN treated at two sites (Toronto and New York) through in-patient or partial hospitalization achieved a minimally normal weight and were then randomly assigned to receive fluoxetine or placebo along with cognitive behavioral therapy (CBT) for 1 year. Clinical, demographic and psychometric variables were assessed after weight restoration prior to randomization and putative predictors of successful weight maintenance at 6 and 12 months were examined. RESULTS The most powerful predictors of weight maintenance at 6 and 12 months following weight restoration were pre-randomization body mass index (BMI) and the rate of weight loss in the first 28 days following randomization. Higher BMI and lower rate of weight loss were associated with greater likelihood of maintaining a normal BMI at 6 and 12 months. An additional predictor of weight maintenance was site; patients in Toronto fared better than those in New York. CONCLUSIONS This study found that the best predictors of weight maintenance in weight-restored AN patients over 6 and 12 months were the level of weight restoration at the conclusion of acute treatment and the avoidance of weight loss immediately following intensive treatment. These results suggest that outcome might be improved by achieving a higher BMI during structured treatment programs and on preventing weight loss immediately following discharge from such programs.

Influence of overanxious disorder of childhood on the expression of anorexia nervosa

OBJECTIVE Childhood anxiety often precedes the onset of anorexia nervosa (AN) and may mark a liability to the emergence of an eating disorder for some women. This study investigates the prevalence of overanxious disorder (OAD) among women with AN and explores how OAD impacts AN symptoms and personality traits. METHOD Participants were 637 women with AN who completed an eating disorders history, the Structured Clinical Interview for DSM-IV Axis I Disorders, and assessments for childhood anxiety, eating disorder attitudes, and associated personality traits. RESULTS Of 249 women (39.1%) reporting a history of OAD, 235 (94.4%) met criteria for OAD before meeting criteria for AN. In comparison to those without OAD, women with AN and OAD self-reported more extreme personality traits and attitudes and they engaged in more compensatory behaviors. CONCLUSION Among individuals with AN, those entering AN on a pathway via OAD present with more severe eating disorder pathology.

Linkage analysis of anorexia and bulimia nervosa cohorts using selected behavioral phenotypes as quantitative traits or covariates

To increase the likelihood of finding genetic variation conferring liability to eating disorders, we measured over 100 attributes thought to be related to liability to eating disorders on affected individuals from multiplex families and two cohorts: one recruited through a proband with anorexia nervosa (AN; AN cohort); the other recruited through a proband with bulimia nervosa (BN; BN cohort). By a multilayer decision process based on expert evaluation and statistical analysis, six traits were selected for linkage analysis (1): obsessionality (OBS), age at menarche (MENAR), and anxiety (ANX) for quantitative trait locus (QTL) linkage analysis; and lifetime minimum body mass index (BMI), concern over mistakes (CM), and food‐related obsessions (OBF) for covariate‐based linkage analysis. The BN cohort produced the largest linkage signals: for QTL linkage analysis, four suggestive signals: (for MENAR, at 10p13; for ANX, at 1q31.1, 4q35.2, and 8q13.1); for covariate‐based linkage analyses, both significant and suggestive linkages (for BMI, one significant [4q21.1] and three suggestive [3p23, 10p13, 5p15.3]; for CM, two significant [16p13.3, 14q21.1] and three suggestive [4p15.33, 8q11.23, 10p11.21]; and for OBF, one significant [14q21.1] and five suggestive [4p16.1, 10p13.1, 8q11.23, 16p13.3, 18p11.31]). Results from the AN cohort were far less compelling: for QTL linkage analysis, two suggestive signals (for OBS at 6q21 and for ANX at 9p21.3); for covariate‐based linkage analysis, five suggestive signals (for BMI at 4q13.1, for CM at 11p11.2 and 17q25.1, and for OBF at 17q25.1 and 15q26.2). Overlap between the two cohorts was minimal for substantial linkage signals.

Two year follow-up of bulimia nervosa: The importance of abstinence as the criterion of outcome

The goal of this pilot follow-up study was to implement operationally defined criteria to classify outcome status of female patients with a DSM-111-R diagnosis of bulimia nervosa 2 years after completion of an intensive group treatment program (N = 43). Specifically, the importance of abstinence from bulimic behaviors as a marker of well-being was investigated. Repeated measures analysis of variance revealed that across most measures of psychopathology, scores for patients who were totally abstinent of hinging and purging were found to be significantly lower than even mildly symptomatic patients (p <.05). A secondary goal of the study was to extend the results of an earlier evaluation of the treatment program by reporting posttreatment results on a larger sample of bulimic patients (N = 86). Overall, the results suggest that a behavioral criterion of abstinence from hinging and purging is critical for the assessment of treatment response and long-term outcome status in bulimia nervosa.

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.

Selection of eating-disorder phenotypes for linkage analysis.

Vulnerability to anorexia nervosa (AN) and bulimia nervosa (BN) arise from the interplay of genetic and environmental factors. To explore the genetic contribution, we measured over 100 psychiatric, personality, and temperament phenotypes of individuals with eating disorders from 154 multiplex families accessed through an AN proband (AN cohort) and 244 multiplex families accessed through a BN proband (BN cohort). To select a parsimonious subset of these attributes for linkage analysis, we subjected the variables to a multilayer decision process based on expert evaluation and statistical analysis. Criteria for trait choice included relevance to eating disorders pathology, published evidence for heritability, and results from our data. Based on these criteria, we chose six traits to analyze for linkage. Obsessionality, Age‐at‐Menarche, and a composite Anxiety measure displayed features of heritable quantitative traits, such as normal distribution and familial correlation, and thus appeared ideal for quantitative trait locus (QTL) linkage analysis. By contrast, some families showed highly concordant and extreme values for three variables—lifetime minimum Body Mass Index (lowest BMI attained during the course of illness), concern over mistakes, and food‐related obsessions—whereas others did not. These distributions are consistent with a mixture of populations, and thus the variables were matched with covariate linkage analysis. Linkage results appear in a subsequent report. Our report lays out a systematic roadmap for utilizing a rich set of phenotypes for genetic analyses, including the selection of linkage methods paired to those phenotypes.

A day hospital program for anorexia nervosa and bulimia

A day hospital group treatment program is detailed which could offer effective treatment to many patients with anorexia nervosa and bulimia nervosa who would otherwise require inpatient treatment. The day hospital program can offer important clinical and financial advantages over an inpatient program. A major difference between the day program and an inpatient setting is the degree of containment offered to the patient and control over the patients behavior. This necessitates important innovations. The day hospital treatment program includes psychological, social, and biological interventions. Most psychological treatment is done in groups. Staff use a multidisciplinary team approach. Potential pitfalls in the program include countertransference reactions and pathological group processes.

Hyperamylasemia and bulimia: A clinical review

Hyperamylasemia, often with abdominal symptoms, commonly occurs in patients with bulimia as well as in pancreatitis. Eleven bulimic patients presenting with hyperamylasemia are described; one case is described in detail. Of the 11, the source of amylase in 10 was salivary, not pancreatic. A careful history with questions about weight changes, eating behavior, body image, methods of weight control and purging, as well as a complete mental status examination should be done on females presenting with the above symptoms. Doing this will prevent unncessary procedures, drug prescription, hospitalizations, and latrogenic illness.

Biomedical variables in the eating disorders

Anorexia nervosa and bulimia nervosa are complex psychosomatic illnesses for which there may be significant biomedical diatheses and sequelae. This paper reviews these biomedical variables, focusing on the medical and nutritional assessment and management of patients with eating disorders and the medical complications that arise in these patients. The paper then examines the relationship between medical illness and eating disorders, including the medical misdiagnoses often given to these patients and the way in which a chronic medical condition such as diabetes mellitus predisposes a patient to an eating disorder. The relationship between eating disorders and pregnancy is also discussed. Through an understanding of these biomedical issues, iatrogenesis can be prevented and treatment can be improved.

Clonidine challenge test in Bulimia nervosa

Recent studies suggest that the α-2 noradrenergic receptor may be of pathophysiologic importance in depression and possibly eating disorders. To assess this further, we administered 1.3 μ/kg i.v. clonidine to 14 bulimics and 11 controls and measured in blood GH, cortisol, MHPG, VMA, HVA, and cardiovascular responses pre- and postperturbation. There were no significant differences between groups in cardiovascular or endocrine responses except for HVA, where baseline levels were higher in controls and demonstrated a greater drop postclonidine than in bulimics. Depressed bulimics responded similarily to nondepressed bulimics. These results are different from those found in depressed patients were there are blunted growth hormone responses to clonidine and differential responses in MHPG, compared with controls, suggesting reduced responsiveness of α-2 noradrenergic receptors. With regard to noradrenergic receptor responsivity, these data do not support shared biologic abnormalities in depression and bulimia nervosa.