Kelly L. Klump

Are Eating Disorders Culture-Bound Syndromes? Implications for Conceptualizing Their Etiology

The authors explore the extent to which eating disorders, specifically anorexia nervosa (AN) and bulimia nervosa (BN), represent culture-bound syndromes and discuss implications for conceptualizing the role genes play in their etiology. The examination is divided into 3 sections: a quantitative meta-analysis of changes in incidence rates since the formal recognition of AN and BN, a qualitative summary of historical evidence of eating disorders before their formal recognition, and an evaluation of the presence of these disorders in non-Western cultures. Findings suggest that BN is a culture-bound syndrome and AN is not. Thus, heritability estimates for BN may show greater variability cross-culturally than heritability estimates for AN, and the genetic bases of these disorders may be associated with differential pathoplasticity.

Academy for eating disorders position paper: Eating disorders are serious mental illnesses

It is the position of the Academy for Eating Disorders (AED) that anorexia nervosa and bulimia nervosa, along with their variants, are biologically based, serious mental illnesses (BBMI) that warrant the same level and breadth of health care coverage as conditions currently categorized in this way (e.g., schizophrenia, bipolar disorder, depression, obsessive-compulsive disorder). As set forth below, we advocate this position unequivocally based on an emerging science that affirms with a reasonable degree of medical and scientific certainty that eating disorders are significantly heritable; influenced by alterations of brain function; significantly impair cognitive function, judgment, and emotional stability; and restrict the life activities of persons afflicted with these illnesses. Accordingly, the denial or restriction of equitable and sufficient treatment necessary to avert serious health consequences and risk of death is untenable and should be vigorously protested. Commentary

Genetic and environmental influences on anorexia nervosa syndromes in a population–based twin sample

BACKGROUND Genetic and environmental influences on broadly-defined anorexia nervosa (AN) syndrome were examined in a population-based twin sample. METHODS AN syndrome was assessed in 672 female 17 year-old twins using structured interviews and a self-report questionnaire. RESULTS Twenty-six probands with AN syndrome were identified. Biometrical model-fitting analyses indicated that genetic and non-shared environmental factors accounted for 74% and 26% of the variance in AN syndrome, respectively. CONCLUSIONS Findings support previous research indicating significant genetic and non-shared environmental influences on AN syndromes.

Age differences in genetic and environmental influences on eating attitudes and behaviors in preadolescent and adolescent female twins

A sample of 680 11- and 602 17-year-old female twins was used to examine (a) age differences in genetic and environmental influences on disordered eating attitudes and behaviors and (b) associations between body mass index (BMI) and eating attitudes and behaviors. Univariate, biometrical model-fitting analyses indicated that 11-year-old twins exhibited less genetic and greater shared environmental influence on eating attitudes and behaviors than 17-year-old twins. Bivariate model-fitting analyses indicated that the relationship between BMI and eating attitudes was mediated primarily by common shared environmental influences in 11-year-old twins and common genetic influences in 17-year-old twins. Nonetheless, the majority of genetic influences on eating attitudes and behaviors in older twins were due to genetic effects that are independent of those operating in BMI.

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.

Three to Four Year Prospective Evaluation of Personality and Behavioral Risk Factors for Later Disordered Eating in Adolescent Girls and Boys

Findings of a 3- to 4-year prospective investigation of personality, temperament, and behavioral factors predictive of the later development of disordered eating in an adolescent population are presented. The sample consisted of 726 girls and 698 boys who entered the study in grades 7–10 in year 1 or in grade 7 in year 2. Predictors of eating disorder risk score were determined separately by gender. For both girls and boys, the latent variable of negative affect/attitudes determined at study entrance was the only significant predictor of final-year risk score. Semistructured diagnostic interviews confirmed an eating disorder diagnosis in 52.8% of 36 female subjects in the high eating disorder symptom group. A substantial history of lifetime and current comorbidity also was noted in this group. The function of negative affect/attitudes as a generalized psychopathology vulnerability factor and as a specific factor increasing risk for disordered eating is discussed.

Significant Linkage on Chromosome 10p in Families with Bulimia Nervosa

Bulimia nervosa (BN) is strongly familial, and additive genetic effects appear to contribute substantially to the observed familiality. In turn, behavioral components of BN, such as self-induced vomiting, are reliably measured and heritable. To identify regions of the genome harboring genetic variants conferring susceptibility to BN, we conducted a linkage analysis of multiplex families with eating disorders that were identified through a proband with BN. Linkage analysis of the entire sample of 308 families yielded a double peak, with the highest nonparametric multipoint maximum LOD score (MLS), of 2.92, on chromosome 10. Given the high heritability of self-induced vomiting and the reliability with which it can be measured, we performed linkage analysis in a subset (n=133) of families in which at least two affected relatives reported a symptom pattern that included self-induced vomiting. The highest MLS (3.39) observed was on chromosome 10, between markers D10S1430 and D10S1423. These results provide evidence of the presence of a susceptibility locus for BN on chromosome 10p. Using simulations, we demonstrate that both of these scores, 2.92 and 3.39, meet the widely accepted criterion for genomewide significance. Another region on 14q meets the criterion for genomewide suggestive linkage, with MLSs of 1.97 (full sample) and 1.75 (subset) at 62 centimorgans from p-ter.

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.

A search for susceptibility loci for anorexia nervosa: methods and sample description

BACKGROUND Eating disorders have not traditionally been viewed as heritable illnesses; however, recent family and twin studies lend credence to the potential role of genetic transmission. The Price Foundation funded an international, multisite study to identify genetic factors contributing to the pathogenesis of anorexia nervosa (AN) by recruiting affective relative pairs. This article is an overview of study methods and the clinical characteristics of the sample. METHODS All probands met modified DSM-IV criteria for AN; all affected first, second, and third degree relatives met DSM-IV criteria for AN, bulimia nervosa (BN), or eating disorder not otherwise specified (NOS). Probands and affected relatives were assessed diagnostically with the Structured Interview for Anorexia and Bulimia. DNA was collected from probands, affected relatives and a subset of their biological parents. RESULTS Assessments were obtained from 196 probands and 237 affected relatives, over 98% of whom are of Caucasian ancestry. Overall, there were 229 relative pairs who were informative for linkage analysis. Of the proband-relative pairs, 63% were AN-AN, 20% were AN-BN, and 16% were AN-NOS. For family-based association analyses, DNA has been collected from both biological parents of 159 eating-disordered subjects. Few significant differences in demographic characteristics were found between proband and relative groups. CONCLUSIONS The present study represents the first large-scale molecular genetic investigation of AN. Our successful recruitment of over 500 subjects, consisting of affected probands, affected relatives, and their biological parents, will provide the basis to investigate genetic transmission of eating disorders via a genome scan and assessment of candidate genes.

Disordered eating in adolescent males from a school-based sample.

OBJECTIVE The authors sought to describe a sample of adolescent males who reported disordered eating, to explore whether males with disordered eating are overweight or obese, and to determine if patterns displayed by females would be replicated with a male sample. METHOD Three school-based adolescent samples were selected. (1) 27 males reporting disordered eating (2) 27 physically matched controls, and (3) 27 randomly selected controls. RESULTS Findings indicated that boys reporting disordered eating expressed greater body dissatisfaction, depression, restraint, and poorer interoceptive awareness compared to matched and randomly selected controls. Negative Emotionality and poor Interoceptive Awareness scores showed the strongest associations with eating pathology. Body mass index and Negative Emotionality scores showed the strongest relationships to restrained eating. DISCUSSION Previous results for female adolescents were replicated, suggesting that findings for females can be generalized to males. Disordered eating appears to exist in the absence of significant weight problems in adolescent males.