Childhood eating and weight in eating disorders: a multi-centre European study of affected women and their unaffected sisters

BACKGROUND: Previous studies have suggested that childhood eating and weight problems may be risk factors for eating disorders. Robust evidence is still lacking. AIMS: To investigate whether childhood eating and weight problems increase the risk of eating disorders in affected women compared to their unaffected sisters. METHODS: Women (150) with anorexia (AN) or bulimia nervosa (BN) recruited from clinical and community samples were compared to their unaffected sister closest in age on maternal reports of childhood eating and weight. RESULTS: Women with BN were significantly more overweight at the ages of 5 and 10 (both OR = 2.8, p < 0.01), ate a lot (OR = 1.3, p < 0.01), were less picky (OR = 0.6, p < 0.05) and ate quickly (OR = 2.3, p < 0.05) between the ages of 6 and 10 compared to their healthy sisters. Significantly more women with AN were described as having a higher weight at 6 months (OR = 0.8, p < 0.01) and 1 year (OR = 0.6, p < 0.01) compared to their healthy sisters. Childhood eating was comparable in the women with AN and their unaffected sisters. CONCLUSIONS: Traits of childhood overeating were more common in bulimic women compared to their unaffected siblings. Subjects with AN did not differ from their sisters on eating variables. The increased risk of BN due to childhood overweight suggests that prevention strategies for childhood obesity and overweight may therefore be applicable in BN.     

Personality features of women with good outcome from restricting anorexia nervosa

Personality characteristics were assessed in women who had physically and, in the majority, psychologically recovered from restricting anorexia nervosa at an 8- to 10-year follow-up. Personality dimensions were evaluated using the Multidimensional Personality Questionnaire, the California Personality Inventory, and the Reid-Ware Scale. Women who had recovered from anorexia nervosa rated higher on risk avoidance, displayed greater restraint in emotional expression and initiative, and showed greater conformance to authority than age-matched normal women. On comparison with their sisters, the recovered women reported a greater degree of self- and impulse control and less enterprise and spontaneity; sisters, however, endorsed equally high moral standards. The differences in personality characteristics remained significant after statistically controlling for depressive symptoms and eating behavior. The results suggest that a temperamental disposition toward emotional and behavioral restraint combined with a strong sense for traditional values may be psychological risk factors for the development of the restricting type of anorexia nervosa.     

Does intra-uterine growth discordance predict differential risk for adult psychiatric disorder in a population-based sample of monozygotic twins?

The study of discordant monozygotic twins may identify important developmental risk factors for adult psychiatric disorder. Differential experience in utero is one candidate environmental risk factor that may distinguish monozygotic twins. In this report, we examine whether intra-pair differences in birth weight predicts discordance for adult psychiatric disorders in 527 female monozygotic twin pairs from a population-based twin registry. Twins were personally interviewed about their lifetime history of DSM-III-R alcoholism, anorexia nervosa, bulimia nervosa, generalized anxiety disorder, major depression, panic disorder, social phobia and simple phobia. Birth weight was estimated from birth certificates, or from retrospective maternal, paternal and self-reports. Conditional logistic regression is used to characterize the association between intra-pair differences in birth weight and discordance for psychiatric disorder in monozygotic twins. The twin with the heavier birth weight in discordant pairs is (insignificantly) more likely to have a history of alcoholism or bulimia. The twin with the lighter birth weight in discordant pairs is (insignificantly) more likely to have a history of major depression, simple phobia, panic disorder, anorexia nervosa, social phobia or generalized anxiety disorder. For all psychiatric disorders examined, the lighter (or heavier) co-twin at birth is not systematically the affected twin within discordant pairs.     

Anorexia nervosa--two cases in discordant MZ twins

Two female monozygous twin pairs discordant for anorexia nervosa are reported, and literature reports on 18 other monozygous pairs are reviewed. Four of the reported pairs are inadequately described and there is doubt about the diagnosis. When the 2 pairs reported here are included, 16 pairs remain: l (38%) were concordant and 10 discordant. Only 3 pairs fulfilled rigorous criteria for anorexia nervosa and zygosity and one of the pairs was concordant. The population prevalence is probably about 2 promille for hospitalized cases, and there is a 6% risk for female sibs of anorectic probands. Hence, if about 1/3 of monozygotic pairs are in fact concordant, a role of genetic factors in the etiology may be suggested.     

What predicts suicide attempts in women with eating disorders?

BACKGROUND: Suicide is a common cause of death in anorexia nervosa and suicide attempts occur often in both anorexia nervosa and bulimia nervosa. No studies have examined predictors of suicide attempts in a longitudinal study of eating disorders with frequent follow-up intervals. The objective of this study was to determine predictors of serious suicide attempts in women with eating disorders. METHOD: In a prospective longitudinal study, women diagnosed with either DSM-IV anorexia nervosa (n = 136) or bulimia nervosa (n = 110) were interviewed and assessed for suicide attempts and suicidal intent every 6-12 months over 8.6 years. RESULTS: Fifteen percent of subjects reported at least one prospective suicide attempt over the course of the study. Significantly more anorexic (22.1%) than bulimic subjects (10.9%) made a suicide attempt. Multivariate analyses indicated that the unique predictors of suicide attempts for anorexia nervosa included the severity of both depressive symptoms and drug use over the course of the study. For bulimia nervosa, a history of drug use disorder at intake and the use of laxatives during the study significantly predicted suicide attempts. CONCLUSIONS: Women with anorexia nervosa or bulimia nervosa are at considerable risk to attempt suicide. Clinicians should be aware of this risk, particularly in anorexic patients with substantial co-morbidity.     

A preliminary population-based twin study of self-reported eating disorder

BACKGROUND: Twin studies have concluded that there is a substantial genetic contribution to the aetiology of eating disorders. The aim of the present study was to estimate the genetic contribution to the aetiology of self-reported eating disorders in a sample of representative twins. METHOD: A population cohort of 34142 young Danish twins was screened for eating disorders by a mailed questionnaire. RESULTS: Concordance rates differed significantly across monozygotic and dizygotic twin pairs for broadly defined self-reported anorexia nervosa and bulimia nervosa. Heritability estimates of 0.48, 0.52 and 0.61 respectively were estimated for narrow and broad definitions of self-reported anorexia nervosa and for self-reported bulimia nervosa. CONCLUSIONS: There is a genetic contribution to the aetiology of self-reported eating disorders in the general population. The relationship between self-reported and clinical eating disorder remains to be examined.     

Shared genetic and environmental risk factors between undue influence of body shape and weight on self-evaluation and dimensions of perfectionism

BACKGROUND: Theory and evidence strongly suggest that perfectionism may be a risk factor for eating disorders. The purpose of the current study was to investigate a model that would explain the relationship between the cognitive diagnostic criterion for both anorexia nervosa and bulimia nervosa, namely undue influence of body weight or shape on self-evaluation, and dimensions of perfectionism. The model of particular interest was the common cause model, which hypothesizes that the phenotypes are caused by the same underlying genetic and environmental risk factors. METHOD: Female twins (n=1002) from the Australian Twin Registry (ATR), aged 28 to 39 years, were interviewed using the Eating Disorder Examination (EDE). In addition, questions relating to the Equal Environment Assumption (EEA) and the Frost Multidimensional Perfectionism Scale, namely concern over mistakes (CM), personal standards (PS) and doubts about actions (DA), were assessed. RESULTS: There was no evidence of violation of the EEA for any of the four phenotypes. Univariate models showed all phenotypes to be influenced by both genetic and non-shared environmental action, where genetic estimates ranged from 25% to 39% of the variance. Multivariate analyses suggested the best explanation of covariation among the phenotypes was an independent pathways, rather than a common pathways, model. CONCLUSIONS: Undue influence of body weight or shape on self-evaluation shared about 10% of its sources of genetic and environmental variance with perfectionism, thus suggesting that a common cause model does not represent the best explanation of the relationship between perfectionism and this cognitive diagnostic criterion for eating disorders.     

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.     

Concurrence of anorexia nervosa and yellow mutant albinism.

A review of published clinical reports shows that anorexia nervosa has been found in association with several genetic anomalies, principally gonosomal aneuploidy. An additional, and unique, association is described here: a case of anorexia nervosa in a patient with the yellow mutant form of oculocutaneous albinism and no other apparent chromosomal abnormalities. While the concurrence of these two disorders in a single person is apparently a chance phenomenon, our review of experimental publications shows that feeding disturbances also occur in yellow mutant mice. Such complementary findings suggest the need for continuing investigation of the genetic foundations of eating behaviour.     

QT interval and QT dispersion in eating disorders

BACKGROUND: Eating disorders are thought to be risk factors for cardiac sudden death secondary to arrhythmia. Results in previous studies on QT interval and QT dispersion, markers of fatal arrhythmia, have been inconsistent. METHODS: We prospectively examined 179 female eating disorder patients, being over 18 years old and diagnosed according to the DSM-IV criteria between January 1995 and December 2002, and 52 healthy women. Patients with abnormal plasma electrolytes or taking medications that might influence the electrocardiogram (ECG) were excluded from the study. QT intervals were corrected for heart rate using Bazett's formula and the nomogram method, which is more reliable at extremely low heart rates than Bazett's formula. QT dispersion was measured as the difference between the longest and shortest QT intervals. QT intervals and QT dispersion in each patient group were compared with those in the control group. RESULTS: The 164 eligible patients consisted of 43 patients with anorexia nervosa restricting type, 35 with anorexia nervosa binge eating/purging type, 63 with bulimia nervosa purging type, and 23 with bulimia nervosa non-purging type. There was no significant difference in age between eating disorder patients and controls. QT interval and QT dispersion were significantly longer in all eating disorder subtypes than in the control group. QT interval and QT dispersion were significantly correlated with the rate of body weight loss in bulimia nervosa. CONCLUSIONS: QT interval and QT dispersion were prolonged in both anorexia nervosa and bulimia nervosa. Examination of ECG in eating disorder patients without extremely low body weight also appears to be clinically important.     

Screening for Axis II personality disorders in women with bulimic eating disorders

The Personality Diagnostic Questionnaire (PDQ) was completed by 628 eating-disordered women: 300 with normal-weight bulimia, 15 with anorexia nervosa with bulimic features, and 313 with subdiagnostic eating disorders. Three-quarters (75%) of subjects with normal-weight bulimia had personality disorder diagnoses, compared with 50% of those with subdiagnostic eating disorders. The average number of separate PDQ diagnoses was 2.7 for the normal-weight bulimia group, 2.5 for the group with anorexia nervosa with bulimic traits, and 1.5 for the subdiagnostic group. The most common PDQ diagnoses were schizotypal, histrionic, and borderline disorders, but avoidant and dependent personality features also occurred. Personality disturbances may be common in patients with eating disorders.     

Association of catecholamine-O-methyltransferase and 5-HTTLPR genotype with eating disorder-related behavior and attitudes in females with eating disorders

OBJECTIVE: There is growing evidence, that genetic variants contribute to the pathogenesis of anorexia nervosa and bulimia nervosa. Genetic studies have revealed candidate genes, but no satisfactory associations with the disorders have been found so far. The aim of the present study was to evaluate, whether behavioral and attitudinal traits of the disorders can serve as phenotypes with a possible association with two common functional polymorphisms of the monoaminergic pathways. METHOD: Forty-five female in-patients of a specialized hospital for eating disorders were included into the study. Eating disorder symptomatology was assessed using the Eating Disorder Inventory-2. The functional catecholamine-O-methyltransferase (COMT) 158 Val-->Met polymorphism and the deletion/insertion polymorphism of the serotonin transporter promoter 5-HTTLPR were determined. RESULTS: Carriers of at least one Met-allele of the COMT gene had significantly higher total scores of the Eating Disorder Inventory-2, as well as significantly higher scores on the subscales bulimia, ineffectiveness, interoceptive awareness, maturity fears and impulse regulation. Carriers of the deletion of the 5-HTTLPR had significantly higher scores on the subscales drive for thinness and body dissatisfaction. CONCLUSION: We found associations between the COMT and the 5-HTTLPR polymorphisms and specific clinical, behavioral and attitudinal traits of eating disorders. These polymorphisms may predispose their carriers to exhibit certain symptoms of eating disorders or confer a general risk for more severe forms of these disorders.     

The childhood and family background of women with clinical eating disorders: a comparison with women with major depression and women without psychiatric disorder

BACKGROUND: Childhood antecedents are often put forward as being of possible aetiological significance for both anorexia nervosa and bulimia nervosa. METHOD: Comparisons were made of groups of women with eating disorders with groups of women with major depression or without current psychiatric disorder, using the Childhood Experience of Care and Abuse interview (CECA). RESULTS: Women with bulimia nervosa (or mixed bulimia and anorexia nervosa) tended to report more troubled childhood experiences than did women from the non-morbid comparison group. In this respect, they resembled those with major depression. In contrast, those with anorexia nervosa resembled the non-morbid women rather than the other psychiatric groups. CONCLUSIONS: Adversity in childhood as measured by the CECA may play a part in the causation of bulimia nervosa but not of anorexia nervosa. It remains possible that more specific or subtle family influences may be relevant.     

Pregnancy and perinatal complications associated with risks for common psychiatric disorders in a population-based sample of female twins.

The association between pregnancy and perinatal complications (PPCs) and risks for adult psychiatric disorders other than psychoses has received relatively limited attention. In this study, we aim to characterize the associations between PPCs and risks for anxiety, affective, substance use, and eating disorders in a population-based sample of twins. Personal interviews were conducted with 1,806 female twin subjects to assess their lifetime history of alcoholism, anorexia nervosa, bulimia nervosa, generalized anxiety disorder, major depression, panic disorder, simple phobias, and social phobias. PPCs were retrospectively assessed at personal interview with the subject's parents. The associations between PPCs and risks for psychiatric disorders are characterized using logistic regression. In this sample of twins, gestational age is associated with a significantly increased risk for anorexia nervosa and pregnancy complications are associated with a significantly increased risk for both anorexia nervosa and bulimia nervosa. Pregnancy and perinatal complications may be associated with an increased risk for eating disorders in women.     

Do illness characteristics and familial risk differ between women with anorexia nervosa grouped on the basis of personality pathology?

BACKGROUND: In view of the potential utility of personality-based groupings in eating disorders (EDs), and the lack of studies using this approach in large samples of individuals with anorexia nervosa (AN), this study set out to examine (i) the nature of personality-based clusters of women with lifetime AN and (ii) if these clusters are associated with either clinical symptoms or aetiological variables. METHOD: The self-report Dimensional Assessment of Personality Pathology (DAPP) was completed by 153 women with a lifetime diagnosis of DSM-IV AN. A cluster analysis was used to identify personality-based subgroups. Clusters were then compared on clinical and aetiological variables. RESULTS: Three personality-based clusters were identified, defined by broad, avoidant and compulsive types of personality pathology. Dimensions of low dissocial behaviour, high inhibition and high compulsivity were common to all clusters, while dimensions related to emotional dysregulation appeared more heterogeneous. Clinical symptoms were not related to personality profile with the exception of a trend towards more fasting behaviour in the broad group. The compulsive cluster with the narrowest range of extreme personality traits reported the highest familial risk of eating pathology. CONCLUSIONS: The three clusters identified in our AN sample were similar to those previously identified in broader eating disordered samples. Personality-based clusters did not correspond overall to clinical symptoms but aetiological differences supported their validity. Broader personality pathology indicative of emotional dysregulation, problems with identity and relationships, in addition to core traits, may increase vulnerability to AN in those with less familial risk.     

Linkage analysis of anorexia nervosa incorporating behavioral covariates

Eating disorders, such as anorexia nervosa (AN) and bulimia nervosa (BN), have genetic and environmental underpinnings. To explore genetic contributions to AN, we measured psychiatric, personality and temperament phenotypes of individuals diagnosed with eating disorders from 196 multiplex families, all accessed through an AN proband, as well as genotyping a battery of 387 short tandem repeat (STR) markers distributed across the genome. On these data we performed a multipoint affected sibling pair (ASP) linkage analysis using a novel method that incorporates covariates. By exploring seven attributes thought to typify individuals with eating disorders, we identified two variables, drive-for-thinness and obsessionality, which delimit populations among the ASPs. For both of these traits, or covariates, there were a cluster of ASPs who have high and concordant values for these traits, in keeping with our expectations for individuals with AN, and other clusters of ASPs who did not meet those expectations. When we incorporated these covariates into the ASP linkage analysis, both jointly and separately, we found several regions of suggestive linkage: one close to genome-wide significance on chromosome 1 (at 210 cM, D1S1660; LOD = 3.46, P = 0.00003), another on chromosome 2 (at 114 cM, D2S1790; LOD = 2.22, P = 0.00070) and a third region on chromosome 13 (at 26 cM, D13S894; LOD = 2.50, P = 0.00035). By comparing our results to those implemented using more standard linkage methods, we find the covariates convey substantial information for the linkage analysis.     

Mortality in eating disorders

Crude mortality rates and mortality rates standardized against a British reference population have been calculated for a group of 460 consecutive patients with eating disorders seen between 1971 and 1981 in a tertiary referral centre for eating disorders. Crude mortality rates were 3.3% and 3.1% in the anorexia nervosa and bulimia nervosa groups respectively. Standardized rates demonstrated a six-fold increase in mortality in the anorexia nervosa group. The most common cause of death in this group was found to be suicide, with the risk of death remaining high for at least eight years after initial assessment. Specific associations of increased mortality were: being in the lowest weight group at the time of presentation, and having recurrent hospital admissions for eating problems.     

Cytokines and anorexia nervosa

OBJECTIVE: Recent studies have indicated that the inflammatory cytokines could be implicated in anorexia nervosa and in its complications. To determinate the potential role of interleukins (IL-1, IL-2, IL-4, IL-6, IL-10), interferon (IFN gamma), tumor necrosis factor (TNF-alpha), and transforming growth factor (TGF-beta2) in anorexia nervosa, serum concentrations of these cytokines were measured in patients suffering from anorexia nervosa in comparison to healthy subjects. METHOD: Twenty-nine anorexic women according to DSM-IV criteria participated in the study. The control group consisted of 20 healthy women without eating disorders, mood disorders, and immunological disorders. RESULTS: We find that serum IL-2 and TGF-beta2 concentrations were both significantly decreased in anorexic patients, although the other cytokines did not differ significantly between the two groups. CONCLUSION: Our results show that in patients with anorexia nervosa, there are lower levels of specific cytokines (especially IL-2 and TGF-beta2). These levels may reflect the combination of impaired nutrition and weight loss, therefore, the dysregulation of these cytokines may contribute in anorexia's complications. Follow-up studies should examine the effects of parameters such as starvation, psychopathologic factors, and psychoneuroendocrinological perturbation which could affect interplay between cytokines, neuropeptides, and neurotransmitters.     

Pregnancy and perinatal complications associated with risks for common psychiatric disorders in a population‐based sample of female twins

The association between pregnancy and perinatal complications (PPCs) and risks for adult psychiatric disorders other than psychoses has received relatively limited attention. In this study, we aim to characterize the associations between PPCs and risks for anxiety, affective, substance use, and eating disorders in a population‐based sample of twins. Personal interviews were conducted with 1,806 female twin subjects to assess their lifetime history of alcoholism, anorexia nervosa, bulimia nervosa, generalized anxiety disorder, major depression, panic disorder, simple phobias, and social phobias. PPCs were retrospectively assessed at personal interview with the subject's parents. The associations between PPCs and risks for psychiatric disorders are characterized using logistic regression. In this sample of twins, gestational age is associated with a significantly increased risk for anorexia nervosa and pregnancy complications are associated with a significantly increased risk for both anorexia nervosa and bulimia nervosa. Pregnancy and perinatal complications may be associated with an increased risk for eating disorders in women. © 2001 Wiley‐Liss, Inc.     

Eating behaviors of children in the context of their family environment

Both a family history of obesity and early childhood obesity have been identified as strong predictors of adult obesity risk. The finding that parental obesity, maternal obesity in particular, increases a child's risk for developing obesity suggests that either shared genes, or environment, or likely a combination of both may promote overeating and excessive weight gain in children. Parents not only create food environments for children's early experiences with food and eating, but they also influence their children's eating by modeling their own eating behaviors, taste preferences, and food choices. Thus, it is important to identify intermediary behavioral eating traits which promote overeating and obesity in children and to determine the extent to which associations between eating traits and excessive weight gain in children may be influenced by genetic factors, environmental factors, or both. Behavioral genetic methods can be used to help partition genetic and environmental sources of variability in behavioral traits. The focus of this paper is to review and discuss findings from both short-term experimental and prospective cohort studies on eating behaviors of children at various stages in their lives. Select child eating traits and parent-child resemblances in eating will be further examined in the context of children's home environment and their familial predisposition to obesity.The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009.