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1.  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.
doi:10.1002/ajmg.b.30226
PMCID: PMC2590774  PMID: 16152574
Complex disease; endophenotype; liability; mixture model; regression
2.  The Heritability of Eating Disorders: Methods and Current Findings 
Family, twin, and adoption studies of anorexia nervosa (AN), bulimia nervosa (BN), binge-eating disorder (BED), and the proposed purging disorder presentation (PD) have consistently demonstrated that genetic factors contribute to the variance in liability to eating disorders. In addition, endophenotypes and component phenotypes of eating disorders have been evaluated and provide further insight regarding genetic factors influencing eating disorders and eating disorder diagnostic criteria. Many of these phenotypes have demonstrated substantial heritability. This chapter reviews biometrical genetic methods and current findings from family and twin studies that investigate the role of genes and environment in the etiology of eating disorders. We review the methodology used to estimate heritability, the results of these studies, and discuss the implications of this research for the basic conceptualization of eating disorders and the future value of twin modeling in the molecular genetic era.
doi:10.1007/7854_2010_91
PMCID: PMC3599773  PMID: 21243474
3.  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.
doi:10.1002/eat.20509
PMCID: PMC3755506  PMID: 18236451
anorexia nervosa; eating disorders; bulimia nervosa; psychiatric disorders; genetics; linkage analysis; genomics
4.  Anorexia nervosa trios: behavioral profiles of individuals with anorexianervosa and their parents 
Psychological medicine  2008;39(3):451-461.
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 (~33 %) comprised low symptom probands and mothers with scores in the healthy range. Class 2 (~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 (~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.
doi:10.1017/S0033291708003826
PMCID: PMC3714180  PMID: 18578898
Anorexia nervosa; eating disorder; genetics; temperament
5.  Interspecies genetics of eating disorder traits 
Family and twin studies have indicated that genetic factors play a role in the development of eating disorders, such as anorexia and bulimia nervosa, but novel views and tools may enhance the identification of neurobiological mechanisms underlying these conditions. Here we propose an integrative genetic approach to reveal novel biological substrates of eating disorder traits analogous in mouse and human. For example, comparable to behavioral hyperactivity that is observed in 40-80% of anorexia nervosa patients, inbred strains of mice with different genetic backgrounds are differentially susceptible to develop behavioral hyperactivity when food restricted. In addition, a list of characteristics that are relevant to eating disorders and approaches to their measurement in humans together with potential analogous rodent models has been generated. Interspecies genetics of neurobehavioral characteristics of eating disorders has the potential to open new roads to identify and functionally test genetic pathways that influence neurocircuits relevant for these heterogeneous psychiatric disorders.
doi:10.1002/ajmg.b.30832
PMCID: PMC2660386  PMID: 18646037
6.  Specific common variants of the obesity-associated FTO gene are not associated with 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 1085 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.
doi:10.1002/ajmg.b.31182
PMCID: PMC3249222  PMID: 21438147
7.  The Prevalence and Correlates of Eating Disorders in the National Comorbidity Survey Replication 
Biological psychiatry  2006;61(3):348-358.
Background
Little population-based data exist on the prevalence or correlates of eating disorders.
Methods
Prevalence and correlates of eating disorders from the National Comorbidity Replication, a nationally representative face-to-face household survey (n _ 9282), conducted in 2001–2003, were assessed using the WHO Composite International Diagnostic Interview.
Results
Lifetime prevalence estimates of DSM-IV anorexia nervosa, bulimia nervosa, and binge eating disorder are .9%, 1.5%, and 3.5% among women, and .3% .5%, and 2.0% among men. Survival analysis based on retrospective age-of-onset reports suggests that risk of bulimia nervosa and binge eating disorder increased with successive birth cohorts. All 3 disorders are significantly comorbid with many other DSM-IV disorders. Lifetime anorexia nervosa is significantly associated with low current weight (body-mass index18.5), whereas lifetime binge eating disorder is associated with current severe obesity (body-mass index < _ 40). Although most respondents with 12-month bulimia nervosa and binge eating disorder report some role impairment (data unavailable for anorexia nervosa since no respondents met criteria for 12-month prevalence), only a minority of cases ever sought treatment.
Conclusions
Eating disorders, although relatively uncommon, represent a public health concern because they are frequently associated with other psychopathology and role impairment, and are frequently under-treated.
doi:10.1016/j.biopsych.2006.03.040
PMCID: PMC1892232  PMID: 16815322
Anorexia nervosa; binge eating disorder; bulimia nervosa; eating disorders; epidemiology; national comorbidity survey replication (NCS-R)
8.  Eating disorder predisposition is associated with ESRRA and HDAC4 mutations  
The Journal of Clinical Investigation  2013;123(11):4706-4713.
Anorexia nervosa and bulimia nervosa are common and severe eating disorders (EDs) of unknown etiology. Although genetic factors have been implicated in the psychopathology of EDs, a clear biological pathway has not been delineated. DNA from two large families affected by EDs was collected, and mutations segregating with illness were identified by whole-genome sequencing following linkage mapping or by whole-exome sequencing. In the first family, analysis of twenty members across three generations identified a rare missense mutation in the estrogen-related receptor α (ESRRA) gene that segregated with illness. In the second family, analysis of eight members across four generations identified a missense mutation in the histone deacetylase 4 (HDAC4) gene that segregated with illness. ESRRA and HDAC4 were determined to interact both in vitro in HeLa cells and in vivo in mouse cortex. Transcriptional analysis revealed that HDAC4 potently represses the expression of known ESRRA-induced target genes. Biochemical analysis of candidate mutations revealed that the identified ESRRA mutation decreased its transcriptional activity, while the HDAC4 mutation increased transcriptional repression of ESRRA. Our findings suggest that mutations that result in decreased ESRRA activity increase the risk of developing EDs.
doi:10.1172/JCI71400
PMCID: PMC3809805  PMID: 24216484
9.  Prevalence of eating disorders in three Cambridge general practices: hidden and conspicuous morbidity. 
The aims of this study were to investigate the prevalence of anorexia nervosa, bulimia nervosa and partial syndromes in women general practice attenders to establish the relative proportions of 'conspicuous' and 'hidden' morbidity. A consecutive series of 540 women patients aged 16-35 years attending their family doctor were screened using a specially devised questionnaire, the weight and dietary practices survey. A total of 115 patients were selected for further assessment and of these 101 patients were interviewed using a standardized diagnostic interview for DSM III-R eating disorders. The prevalence of anorexia nervosa was 0.2% (one case), of bulimia nervosa 1.5% (eight cases) and of partial syndrome bulimia nervosa 5.4% (29 cases). Half of the cases of bulimia nervosa had not been identified by the general practitioner and two of these patients had been referred to specialists for treatment of secondary complications of the eating disorder. Hidden cases of bulimia nervosa or partial syndromes are relatively common in general practice. Certain key questions could be used by general practitioners in order to identify women with eating disorders.
PMCID: PMC1371924  PMID: 1493006
10.  Not all my fault”: Genetics, stigma, and personal responsibility for women with eating disorders 
Social science & medicine (1982)  2012;75(8):1408-1416.
Medical researchers and clinicians increasingly understand and present eating disorders (anorexia and bulimia nervosa) as biologically-based psychiatric disorders, with genetic risk factors established by high heritability estimates in twin studies. But there has been no research on interpretation of genetic involvement by people with eating disorders, who may hold other views. Their interpretations are particularly important given the frequent presumption that biogenetic framing will reduce stigma, and recent findings that it exacerbates stigma for other mental illnesses. To identify implications of genetic framing in eating disorders, I conducted semi-structured interviews with 50 US women with a history of eating disorders (half recovered, half in treatment; interviewed 2008–9 in the USA). Interviews introduced the topic of genetics, but not stigma per se. Analysis followed the general principles of grounded theory to identify perceived implications of genetic involvement; those relevant to stigma are reported here. Most anticipated that genetic reframing would help reduce stigma from personal responsibility (i.e., blame and guilt for eating disorder as ongoing choice). A third articulated ways it could add stigma, including novel forms of stigma related to genetic essentialist effacing of social factors. Despite welcoming reductions in blame and guilt, half also worried genetic framing could hamper recovery, by encouraging fatalistic self-fulfilling prophecies and genetic excuses. This study is the first to elicit perceptions of genetic involvement by those with eating disorders, and contributes to an emerging literature on perceptions of psychiatric genetics by people with mental illness.
doi:10.1016/j.socscimed.2012.05.042
PMCID: PMC3495131  PMID: 22819736
USA; stigma; eating disorders; genetics; women; anorexia nervosa; bulimia nervosa; mental illness
11.  Psychological and weight-related characteristics of patients with anorexia nervosa-restricting type who later develop bulimia nervosa 
Background
Patients with anorexia nervosa-restricting type (AN-R) sometimes develop accompanying bulimic symptoms or the full syndrome of bulimia nervosa (BN). If clinicians could predict who might change into the bulimic sub-type or BN, preventative steps could be taken. Therefore, we investigated anthropometric and psychological factors possibly associated with such changes.
Method
All participants were from a study by the Japanese Genetic Research Group for Eating Disorders. Of 80 patients initially diagnosed with AN-R, 22 changed to the AN-Binge Eating/Purging Type (AN-BP) and 14 to BN for some period of time. The remaining 44 patients remained AN-R only from the onset to the investigation period. Variables compared by ANOVA included anthropometric measures, personality traits such as Multiple Perfectionism Scale scores and Temperament and Character Inventory scores, and Beck Depression Inventory-II scores.
Results
In comparison with AN-R only patients, those who developed BN had significantly higher current BMI (p < 0.05) and maximum BMI in the past (p < 0.05). They also scored significantly higher for the psychological characteristic of parental criticism (p < 0.05) and lower in self-directedness (p < 0.05), which confirms previous reports, but these differences disappeared when the depression score was used as a co-variant. No significant differences were obtained for personality traits or depression among the AN-R only patients irrespective of their duration of illness.
Conclusion
The present findings suggest a tendency toward obesity among patients who cross over from AN-R to BN. Low self-directedness and high parental criticism may be associated with the development of BN by patients with AN-R, although the differences may also be associated with depression.
doi:10.1186/1751-0759-2-5
PMCID: PMC2275291  PMID: 18267038
12.  Exploring the gene–environment nexus in eating disorders 
Early theories of eating disorders focused on aversive family and sociocultural factors as fundamental to the development of these problems. A progression of family, twin and molecular genetic studies has demonstrated a substantial role for genetic factors in the development of anorexia nervosa, bulimia nervosa and related traits. Paradoxically, genetic studies hold promise for refining and enriching our approach to understanding the impact of adverse environmental forces. The development of new and more sophisticated approaches for understanding the complex interplay of genetic and environmental effects will allow enhanced understanding of both risk and protective environmental factors and how they may influence expressions of underlying genetic vulnerabilities to eating disorders.
PMCID: PMC1197278  PMID: 16151538
anorexia nervosa; bulimia nervosa; genetics; environment
13.  The severity and status of eating disorder NOS: Implications for DSM-V 
Behaviour Research and Therapy  2007;45(8):1705-1715.
“Eating disorder NOS” is the most common eating disorder encountered in outpatient settings yet it has been neglected. The aim of this study was to describe the characteristics of eating disorder NOS, establish its severity, and determine whether its high relative prevalence might be due to the inclusion of cases closely resembling anorexia nervosa or bulimia nervosa. One hundred and seventy consecutive patients with an eating disorder were assessed using standardised instruments. Operational DSM-IV diagnoses were made and eating disorder NOS cases were compared with bulimia nervosa cases. Diagnostic criteria were then adjusted to determine the impact on the prevalence of eating disorder NOS. Cases of eating disorder NOS comprised 60.0% of the sample. These cases closely resembled the cases of bulimia nervosa in the nature, duration and severity of their psychopathology. Few could be reclassified as cases of anorexia nervosa or bulimia nervosa. The findings indicate that eating disorder NOS is common, severe and persistent. Most cases are “mixed” in character and not subthreshold forms of anorexia nervosa or bulimia nervosa. It is proposed that in DSM-V the clinical state (or states) currently embraced by the diagnosis eating disorder NOS be reclassified as one or more specific forms of eating disorder.
doi:10.1016/j.brat.2007.01.010
PMCID: PMC2706994  PMID: 17374360
Anorexia nervosa; Bulimia nervosa; Eating disorder; DSM-V; Diagnosis; Classification
14.  An Association Study of the A218C Polymorphism of the Tryptophan Hydroxylase 1 Gene with Eating Disorders in a Korean Population: A Pilot Study 
Psychiatry Investigation  2009;6(1):44-49.
Objective
We examined the association between the tryptophan hydroxylase 1 (TPH1) gene and eating disorders focusing on obsessionality.
Methods
The sample included 62 women with a lifetime diagnosis of anorexia nervosa (AN) as well as 50 women with a lifetime diagnosis of bulimia nervosa (BN) recruited from specialist clinics for eating disorders and 131 healthy women in Korea. Blood samples were collected from all participants for the TPH1 genotyping. The patients were ad ministered the Korean version of the Eating Disorders Examination and obsessionality was conceptualized using measures of persistence, harm avoidance, and obsessive-compulsive symptoms.
Results
In the case-control comparisons, the frequency of the A/A genotype was increased in the patients with BN, but this difference was not significant after correcting for multiple testing. We found no effect of the TPH A218C polymorphism on obsessionality in the patients with AN or BN.
Conclusion
Although the present findings should be regarded as preliminary because of the small size of our sample, they suggest that the TPH1 gene may contribute to the genetic susceptibility to BN and be associated with the other unexplored traits of bulimic case status.
doi:10.4306/pi.2009.6.1.44
PMCID: PMC2796036  PMID: 20046373
Tryptophan hydroxylase; Eating disorders; Bulimia nervosa; Obsessionality
15.  Onset of adolescent eating disorders: population based cohort study over 3 years 
BMJ : British Medical Journal  1999;318(7186):765-768.
Objective
To study the predictors of new eating disorders in an adolescent cohort.
Design
Cohort study over 3 years with six waves.
Subjects
Students, initially aged 14-15 years, from 44 secondary schools in the state of Victoria, Australia.
Outcome measures
Weight (kg), height (cm), dieting (adolescent dieting scale), psychiatric morbidity (revised clinical interview schedule), and eating disorder (branched eating disorders test). Eating disorder (partial syndrome) was defined when a subject met two criteria for either anorexia nervosa or bulimia nervosa according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV).
Results
At the start of the study, 3.3% (29/888) of female subjects and 0.3% (2/811) of male subjects had partial syndromes of eating disorders. The rate of development of new eating disorder per 1000 person years of observation was 21.8 in female subjects and 6.0 in male subjects. Female subjects who dieted at a severe level were 18 times more likely to develop an eating disorder than those who did not diet, and female subjects who dieted at a moderate level were five times more likely to develop an eating disorder than those who did not diet. Psychiatric morbidity predicted the onset of eating disorder independently of dieting status so that those subjects in the highest morbidity category had an almost sevenfold increased risk of developing an eating disorder. After adjustment for earlier dieting and psychiatric morbidity, body mass index, extent of exercise, and sex were not predictive of new eating disorders.
Conclusions
Dieting is the most important predictor of new eating disorders. Differences in the incidence of eating disorders between sexes were largely accounted for by the high rates of earlier dieting and psychiatric morbidity in the female subjects. In adolescents, controlling weight by exercise rather than diet restriction seems to carry less risk of development of eating disorders.
Key messagesAdolescent females who diet at a severe level are 18 times more likely to develop an eating disorder than those who do not diet, and those who diet at a moderate level are five times more likely to develop an eating disorderHigh levels of psychiatric morbidity in females increase the risk of developing eating disorders by sevenfoldAround two thirds of new cases of eating disorder arise in females who have dieted moderatelyThe predominance of eating disorders in females is largely explained by the higher rates of earlier dieting and psychiatric morbidityDaily exercise seems to be a less risky strategy for controlling weight in adolescents
PMCID: PMC27789  PMID: 10082698
16.  A debate on current eating disorder diagnoses in light of neurobiological findings: is it time for a spectrum model? 
BMC Psychiatry  2012;12:76.
Background
Sixty percent of eating disorders do not meet criteria for anorexia- or bulimia nervosa, as defined by the Diagnostic and Statistical Manual version 4 (DSM-IV). Instead they are diagnosed as ‘eating disorders not otherwise specified’ (EDNOS). Discrepancies between criteria and clinical reality currently hampering eating disorder diagnoses in the DSM-IV will be addressed by the forthcoming DSM-V. However, future diagnoses for eating disorders will rely on current advances in the fields of neuroimaging and genetics for classification of symptoms that will ultimately improve treatment.
Discussion
Here we debate the classification issues, and discuss how brain imaging and genetic discoveries might be interwoven into a model of eating disorders to provide better classification and treatment. The debate concerns: a) current issues in the classification of eating disorders in the DSM-IV, b) changes proposed for DSM-V, c) neuroimaging eating disorder research and d) genetic eating disorder research.
Summary
We outline a novel evidence-based ‘impulse control’ spectrum model of eating disorders. A model of eating disorders is proposed that will aid future diagnosis of symptoms, coinciding with contemporary suggestions by clinicians and the proposed changes due to be published in the DSM-V.
doi:10.1186/1471-244X-12-76
PMCID: PMC3475111  PMID: 22770364
DSM; Anorexia; Bulimia; Binge-eating; Genetic; fMRI
17.  Detection, Evaluation, and Treatment of Eating Disorders 
OBJECTIVE
To describe how primary care clinicians can detect an eating disorder and identify and manage the associated medical complications.
DESIGN
A review of literature from 1994 to 1999 identified by a medlinesearch on epidemiology, diagnosis, and therapy of eating disorders, including anorexia nervosa and bulimia nervosa.
MEASUREMENTS AND MAIN RESULTS
Detection requires awareness of risk factors for, and symptoms and signs of, anorexia nervosa (e.g., participation in activities valuing thinness, family history of an eating disorder, amenorrhea, lanugo hair) and bulimia nervosa (e.g., unsuccessful attempts at weight loss, history of childhood sexual abuse, family history of depression, erosion of tooth enamel from vomiting, partoid gland swelling, and gastroesophageal reflux). Providers must also remain alert for disordered eating in female athletes (the female athlete triad) and disordered eating in diabetics. Treatment requires a multidisciplinary team including a primary care practitioner, nutritionist, and mental health professional. The role of the primary care practitioner is to help determine the need for hospitalization and to manage medical complications (e.g., arrhythmias, refeeding syndrome, osteoporosis, and electrolyte abnormalities such as hypokalemia).
CONCLUSION
Primary care providers have an important role in detecting and managing eating disorders.
doi:10.1046/j.1525-1497.2000.02439.x
PMCID: PMC1495575  PMID: 10940151
eating disorders; primary care; medical complications
18.  The relationship between eating disorder not otherwise specified (EDNOS) and officially recognized eating disorders: Meta-analysis and implications for DSM 
Psychological bulletin  2009;135(3):407-433.
Eating disorder not otherwise specified (EDNOS) is the most prevalent eating disorder (ED) diagnosis. This meta-analysis aimed to inform DSM revisions by comparing the psychopathology of EDNOS to that of the officially recognized EDs: anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). A comprehensive literature search identified 125 eligible studies (published and unpublished) appearing in the literature from 1987 to 2007. Random effects analyses indicated that while EDNOS did not differ significantly from AN and BED on eating pathology or general psychopathology, BN exhibited greater eating and general psychopathology than EDNOS. Moderator analyses indicated that EDNOS groups who met all diagnostic criteria for AN except for amenorrhea did not differ significantly from full syndrome cases. Similarly, EDNOS groups who met all criteria for BN or BED except for binge frequency did not differ significantly from full syndrome cases. Results suggest that EDNOS represents a set of disorders associated with substantial psychological and physiological morbidity. While certain EDNOS subtypes could be incorporated into existing DSM-IV categories, others such as purging disorder and non-fat-phobic AN—may be best conceptualized as distinct syndromes.
doi:10.1037/a0015326
PMCID: PMC2847852  PMID: 19379023
Eating disorder not otherwise specified (EDNOS); eating disorder classification; DSM; Meta-analysis
19.  Perception of transgenerational family relationships: Comparison of eating-disordered patients and their parents 
Background
Disturbances in various elements of transgenerational family functioning patterns are not uncommon in studies of eating disorders.
We examined the relationship between patients’ perception of autonomy and intimacy in their families of origin and that of their parents in their own families of origin.
Material/Methods
The sample consisted of 112 girls who had a diagnosis of an eating disoder and their parents; 54 of the girls were diagnosed with anorexia nervosa restrictive subtype, 22 as anorexia nervosa binge/purge subtype, and 36 were diagnosed with bulimia nervosa. We had 2 control groups: 1 group consisted of 36 girls diagnosed with a depressive episode, dysthymia, or adjustment disorder with depressed mood and the other group was 85 female students from schools in Cracow, Poland and their parents. We used the the Family of Origin Scale to assess perception of family relationships. Statistical analysis was performed with the Statistical Package for the Social Sciences (SPSS 20.0.PL; Chicago, IL, USA).
Results
There was a significant association between daughters’ and fathers’ perceptions of autonomy in their families of origin in all groups. There was no significant association between daughters’ and mothers’ perceptions in all groups. The strongest correlation was between the non-clinical sample of girls and their fathers and for the bulimic group.
Conclusions
We did not detect any link indicating the specificity of transgenerational transmission of autonomy and intimacy in eating disorders. The results point to the importance of the father figure in studies of family systems, including the context of family transmission.
doi:10.12659/MSM.889432
PMCID: PMC3867474  PMID: 24309425
anorexia nervosa; bulimia nervosa; family; autonomy; intimacy
20.  Maternal Eating Disorders and Infant Temperament: Findings from the Norwegian Mother and Child Cohort Study 
Objective
We hypothesized that women with eating disorders would be more likely to rate their infants’ temperament higher on negative emotionality than women without eating disorders.
Method
Of 3013 mothers with eating disorders, 44 reported anorexia nervosa (AN), 436 bulimia nervosa (BN), 2475 binge eating disorder (BED), and 58 EDNOS purging type (EDNOS-P). The referent group comprised 45,964 mothers with no eating disorder. A partial proportional odds model was used to estimate the relation among maternal eating disorder presentations and infant temperament ratings, while adjusting for covariates.
Results
Women with AN, BN, EDNOS-P, and BED were 2.30, 1.35, 2.82, and 1.44 times more likely to report extreme fussiness than the referent group of women with no eating disorder, respectively.
Conclusions
Mothers with eating disorders may rate their infants as more difficult because of information processing biases or because their infants are emotionally difficult. Maternal perception of infant temperament may be a risk factor for children’s emotional development.
doi:10.1002/eat.20983
PMCID: PMC3323717  PMID: 22287333
maternal; pregnancy; perinatal depression; eating disorders; infant temperament
21.  Effectiveness of a web-based treatment program using intensive therapeutic support for female patients with bulimia nervosa, binge eating disorder and eating disorders not otherwise specified: study protocol of a randomized controlled trial 
BMC Psychiatry  2013;13:310.
Background
Disordered eating behavior and body dissatisfaction affect a large proportion of the Dutch population and account for severe psychological, physical and social morbidity. Yet, the threshold for seeking professional care is still high. In the Netherlands, only 7.5% of patients with bulimia nervosa and 33% of patients with anorexia nervosa are treated within the mental health care system. Easily accessible and low-threshold interventions, therefore, are needed urgently. The internet has great potential to offer such interventions. The aim of this study is to determine whether a web-based treatment program for patients with eating disorders can improve eating disorder psychopathology among female patients with bulimia nervosa, binge eating disorder and eating disorders not otherwise specified.
Methods/design
This randomized controlled trial will compare the outcomes of an experimental treatment group to a waiting list control group. In the web-based treatment program, participants will communicate personally and asynchronously with their therapists exclusively via the internet. The first part of the program will focus on analyzing eating attitudes and behaviors. In the second part of the program participants will learn how to change their attitudes and behaviors. Participants assigned to the waiting list control group will receive no-reply email messages once every two weeks during the waiting period of 15 weeks, after which they can start the program. The primary outcome measure is an improvement in eating disorder psychopathology as determined by the Eating Disorder Examination Questionnaire. Secondary outcomes include improvements in body image, physical and mental health, body weight, self-esteem, quality of life, and social contacts. In addition, the participants’ motivation for treatment and their acceptability of the program and the therapeutic alliance will be measured. The study will follow the recommendations in the CONSORT statement relating to designing and reporting on RCTs.
Discussion
This study protocol presents the design of a RCT for evaluating the effectiveness of a web-based treatment program using intensive therapeutic support for female patients with bulimia nervosa, binge eating disorder and eating disorders not otherwise specified.
Trial registration
The protocol for this study is registered with the Netherlands Trial Registry NTR2415.
doi:10.1186/1471-244X-13-310
PMCID: PMC3840645  PMID: 24238630
Eating disorders; Bulimia nervosa; Binge eating disorder; Eating disorders not otherwise specified; Randomized controlled trial; Web-based treatment program; e-health; Intensive therapeutic support; Asynchronous support
22.  Effects of milnacipran on binge eating – a pilot study 
Selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors are effective in the treatment of bulimia nervosa. There have been relatively few studies of the efficacy of specific serotonin and norepinephrine reuptake inhibitors in the treatment of eating disorders. Twenty-five outpatients with binge eating episodes, diagnosed as anorexia nervosa, binge-eating/purging type, bulimia nervosa/purging type, or bulimia nervosa/non-purging type, were treated with milnacipran and 20 patients completed the 8-week study. Symptom severity was evaluated using the Bulimic Investigatory Test, Edinburgh (BITE) self-rating scale before administration of milnacipran and after 1, 4, and 8 weeks treatment. The scores improved after 8 weeks, especially drive to, and regret for, binge eating. Milnacipran was more effective in patients without purging and in younger patients, while there was no difference in the efficacy of milnacipran among subtypes of eating disorders.
PMCID: PMC2515919  PMID: 18728825
milnacipran; specific serotonin and norepinephrine reuptake inhibitors; binge eating; vomiting; eating disorder; pharmacotherapy
23.  Genome-Wide Association Analysis of Eating Disorder-Related Symptoms, Behaviors, and Personality Traits 
American Journal of Medical Genetics  2012;159B(7):803-811.
Eating disorders (EDs) are common, complex psychiatric disorders thought to be caused by both genetic and environmental factors. They share many symptoms, behaviors, and personality traits, which may have overlapping heritability. The aim of the present study is to perform a genome-wide association scan (GWAS) of six ED phenotypes comprising three symptom traits from the Eating Disorders Inventory 2 [Drive for Thinness (DT), Body Dissatisfaction (BD), and Bulimia], Weight Fluctuation symptom, Breakfast Skipping behavior and Childhood Obsessive-Compulsive Personality Disorder trait (CHIRP). Investigated traits were derived from standardized self-report questionnaires completed by the TwinsUK population-based cohort. We tested 283,744 directly typed SNPs across six phenotypes of interest in the TwinsUK discovery dataset and followed-up signals from various strata using a two-stage replication strategy in two independent cohorts of European ancestry. We meta-analyzed a total of 2,698 individuals for DT, 2,680 for BD, 2,789 (821 cases/1,968 controls) for Bulimia, 1,360 (633 cases/727 controls) for Childhood Obsessive-Compulsive Personality Disorder trait, 2,773 (761 cases/2,012 controls) for Breakfast Skipping, and 2,967 (798 cases/2,169 controls) for Weight Fluctuation symptom. In this GWAS analysis of six ED-related phenotypes, we detected association of eight genetic variants with P < 10−5. Genetic variants that showed suggestive evidence of association were previously associated with several psychiatric disorders and ED-related phenotypes. Our study indicates that larger-scale collaborative studies will be needed to achieve the necessary power to detect loci underlying ED-related traits. © 2012 Wiley Periodicals, Inc.
doi:10.1002/ajmg.b.32087
PMCID: PMC3494378  PMID: 22911880
Drive for Thinness; Body Dissatisfaction; Childhood Obsessive Compulsive Personality Disorder; Weight Fluctuation; Breakfast Skipping
24.  Diagnostic Crossover in Anorexia Nervosa and Bulimia Nervosa: Implications for DSM-V 
The American journal of psychiatry  2008;165(2):245-250.
Objective
The Diagnostic and Statistical Manual of Mental Disorders (DSM) is designed primarily as a clinical tool. Yet high rates of diagnostic “crossover” among the anorexia nervosa subtypes and bulimia nervosa may reflect problems with the validity of the current diagnostic schema, thereby limiting its clinical utility. This study was designed to examine diagnostic crossover longitudinally in anorexia nervosa and bulimia nervosa to inform the validity of the DSM-IV-TR eating disorders classification system.
Method
A total of 216 women with a diagnosis of anorexia nervosa or bulimia nervosa were followed for 7 years; weekly eating disorder symptom data collected using the Eating Disorder Longitudinal Interval Follow-Up Examination allowed for diagnoses to be made throughout the follow-up period.
Results
Over 7 years, the majority of women with anorexia nervosa experienced diagnostic crossover: more than half crossed between the restricting and binge eating/purging anorexia nervosa subtypes over time; one-third crossed over to bulimia nervosa but were likely to relapse into anorexia nervosa. Women with bulimia nervosa were unlikely to cross over to anorexia nervosa.
Conclusions
These findings support the longitudinal distinction of anorexia nervosa and bulimia nervosa but do not support the anorexia nervosa subtyping schema.
doi:10.1176/appi.ajp.2007.07060951
PMCID: PMC3684068  PMID: 18198267
25.  CHARACTERIZATION OF EATING DISORDERS AFTER BARIATRIC SURGERY: A CASE SERIES STUDY 
Objective
A significant number of post-bariatric surgery patients present with eating disorders (ED) symptoms that require specialized treatment. These cases are thought to be underreported due to their frequent sub-syndromal presentation. This paper describes eating disorder syndromes that develop subsequent to bariatric surgery.
Methods
The clinical charts of 12 individuals who were hospitalized on a specialized inpatient eating disorders unit were reviewed.
Results
Based on the new DSM-5 proposed criteria, six patients would meet criteria for an anorexia nervosa (AN) diagnosis: three with binge eating/purge AN subtype and three with restrictive AN subtype. An additional four met criteria for atypical anorexia nervosa, since they were at a normal weight, and two patients met criteria for bulimia nervosa.
Discussion
Several similarities to the classical EDs were found. The findings that most distinguished these patients from those with classical EDs were their ages, and the age of onset of the ED for some patients.
doi:10.1002/eat.22074
PMCID: PMC3596455  PMID: 23192683
bariatric surgery; post surgery eating disorders; DSM-5

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