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Forschung - Publikationsliste

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J Pediatr Gastroenterol Nutr. 2008 Nov;47(5):555-61.
Quality of life in adolescents with treated coeliac disease: influence of  compliance and age at diagnosis.
Wagner G, Berger G, Sinnreich U, Grylli V, Schober E, Huber WD, Karwautz A.

OBJECTIVE: To assess the influence of gluten-free diet (GFD) compliance on the quality of life (QOL) of adolescents with coeliac disease (CD), and the impact of patient's age at time of diagnosis. STUDY DESIGN: Participants included 365 subjects: 283 adolescents (10-20 years old) with biopsy-proven CD and 82 adolescents without a chronic condition matched for age, sex, education, and social status. Their subjective QOL-comprising physical, mental, and social dimensions as defined by the World Health Organization-was measured and has been analyzed according to compliance status and age at CD diagnosis.
RESULTS: Adolescents noncompliant with GFD reported a lower general QOL, more physical problems, a higher burden of illness, more family problems, and more problems in leisure time than adolescents who are compliant with GFD. More frequent GFD transgressions were associated with poorer QOL. Higher problem anticipation and higher feelings of "ill-being" were found in the noncompliant group. No differences between compliant patients with CD and adolescents without any chronic condition were found in all QOL aspects. Adolescents with a late CD diagnosis showed more problems at school and in social contact with peers, as well as worse physical health and higher CD-associated burden.
CONCLUSIONS: Compliance with GFD is an essential factor to obtain optimal QOL. Psychosocial and educational support should be provided for patients having difficulties strictly adhering to GFD. Early CD onset and diagnosis is associated with better physical health, lower CD-associated burden and fewer social problems, indicating the importance of the earliest CD diagnosis possible.

Psychosomatics 2008 Sep-Oct;49(5):399-406.
Eating pathology in adolescents with celiac disease.
Karwautz A, Wagner G, Berger G, Sinnreich U, Grylli V, Huber WD

BACKGROUND: Celiac disease (CD), treated by a gluten-free diet, may represent a nonspecific trigger for the development of eating pathology, particularly in adolescence. OBJECTIVE: The authors sought to perform a systematic study on eating pathology in CD.
METHOD: CD patients were assessed for eating disorders by questionnaire, and body mass index was recorded.
RESULTS: There was a higher rate of eating pathology in CD patients than would be expected, especially, a higher rate of bulimia nervosa. This subgroup reported more noncompliance with the gluten-free diet and had higher scores on most eating-related questionnaires. In most cases, diagnosis of CD preceded the onset of eating pathology.
CONCLUSION: The authors recommend asking early-adolescent CD patients whether they are also dieting for aesthetic reasons.

Br J Nutr. 2008 Aug 28:1-10. [Epub ahead of print]
Associations of individual and family eating patterns during childhood and early adolescence: a multicentre European study of associated eating disorder factors.
Krug I, Treasure J, Anderluh M, Bellodi L, Cellini E, Collier D, Bernardo MD, Granero R, Karwautz A, Nacmias B, Penelo E, Ricca V, Sorbi S, Tchanturia K, Wagner G, Fernández-Aranda F.

The objective of this study was to examine whether there is an association between individual and family eating patterns during childhood and early adolescence and the likelihood of developing a subsequent eating disorder (ED). A total of 1664 participants took part in the study. The ED cases (n 879) were referred for assessment and treatment to specialized ED units in five different European countries and were compared to a control group of healthy individuals (n 785). Participants completed the Early Eating Environmental Subscale of the Cross-Cultural (Environmental) Questionnaire, a retrospective measure, which has been developed as part of a European multicentre trial in order to detect dimensions associated with ED in different countries. In the control group, also the General Health Questionnaire-28 (GHQ-28), the semi-structured clinical interview (SCID-I) and the Eating Attitudes Test (EAT-26) were used. Five individually Categorical Principal Components Analysis (CatPCA) procedures were adjusted, one for each theoretically expected factor. Logistic regression analyses indicated that the domains with the strongest effects from the CatPCA scores in the total sample were: food used as individualization, and control and rules about food. On the other hand, healthy eating was negatively related to a subsequent ED. When differences between countries were assessed, results indicated that the pattern of associated ED factors did vary between countries. There was very little difference in early eating behaviour on the subtypes of ED. These findings suggest that the fragmentation of meals within the family and an excessive importance given to food by the individual and the family are linked to the later development of an ED.

Drug Alcohol Depend. 2008 Sep 1;97(1-2):169-79. Epub 2008 Jun 20.
Present and lifetime comorbidity of tobacco, alcohol and drug use in eating disorders: a European multicenter study.
Krug I, Treasure J, Anderluh M, Bellodi L, Cellini E, di Bernardo M, Granero R, Karwautz A, Nacmias B, Penelo E, Ricca V, Sorbi S, Tchanturia K, Wagner G, Collier D, Fernández-Aranda F.

OBJECTIVES: To assess the differences in comorbid lifetime and current substance use (tobacco, alcohol and drug use) between eating disorder (ED) patients and healthy controls in five different European countries.
METHOD: A total of 1664 participants took part in the present study. ED cases (n=879) were referred to specialized ED units in five European countries. The ED cases were compared to a balanced control group of 785 healthy individuals.
ASSESSMENT: Participants completed the Substance Use Subscale of the Cross Cultural (Environmental) Questionnaire (CCQ), a measure of lifetime tobacco, alcohol and drug use. In the control group, also the GHQ-28, the SCID-I interview and the EAT-26 were used.
RESULTS: ED patients had higher lifetime and current tobacco and general drug use. The only non-significant result was obtained for lifetime and current alcohol use. Significant differences across ED subdiagnoses and controls also emerged, with BN and AN-BP generally presenting the highest and AN-R and controls the lowest rates. The only exception was detected for alcohol use where EDNOS demonstrated the highest values. Only a few cultural differences between countries emerged.
CONCLUSIONS: With the exception of alcohol consumption, tobacco and drug use appear to be more prevalent in ED patients than healthy controls. The differential risk observed in patients with bulimic features might be related to differences in temperament or might be the result of increased sensitivity to reward.

Psychiatric Genetics 2007 Aug;17(4):247-8.
No association between a promoter polymorphism in the noradrenaline transporter gene and anorexia nervosa.
Hu X, Karwautz A, Li T, Holliday J, Treasure J, Collier DA: 
 

To examine whether there is an association between individual and family eating patterns during childhood and the likelihood of developing an eating disorder (ED) later in life. The sample comprised 261 eating disorder patients [33.5% [N=88] anorexia nervosa (AN), 47.2% [N=123] with bulimia nervosa (BN) and 19.3% [N=50] with Eating Disorders Not Otherwise Specified (EDNOS)] and 160 healthy controls from the Province of Catalonia, Spain, who were matched for age and education. All patients were consecutively admitted to our Psychiatry Department and were diagnosed according to DSM-IV criteria. Participants completed the Early Eating Environmental Subscale of the Cross-Cultural (Environmental) Questionnaire (CCQ), a retrospective measure of childhood eating attitudes and behaviours. In the control group, also the General Health Questionnaire-28 (GHQ-28) was used. During childhood and early adolescence, the following main factors were identified to be linked to eating disorders: eating excessive sweets and snacks and consuming food specially prepared for the respondent. Conversely, regular breakfast consumption was negatively associated with an eating disorder. Compared to healthy controls, eating disorder patients report unfavourable eating patterns early in life, which in conjunction with an excessive importance given to food by the individual and the family may increase the likelihood for developing a subsequent eating disorder.

Psychotherapy and psychosomatics, 2007, 76(4): 234-41
Childhood eating and weight in eating disorders: a multi-centre European study of affected women and their unaffected sisters
N. Micali, J. Holliday, A. Karwautz, M. Haidvogl, G. Wagner, F. Fernandez-Aranda, A. Badia, L. Gimenez, R. Solano, M. Brecelj-Anderluh, R. Mohan, D. Collier and J. L. Treasure

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.

Neuropsychiatrie 2006, 20: 131-134
Essstörungsforschung — neue Ansätze und rezente Ergebnisse bei jugendlichen Populationen.
Karwautz A
 

Österreichische Gesellschaft für Artificial Intelligence—Journal 2006, 25/2: 2-19.  
LinkVis: A novel tool for visualizing and analyzing psychotherapeutic processes.
Ohmann S, Popow C, Schuch B, Lanzenberger M, Herzog H, Karwautz A, Miksch S.
 

Psychiatr Genet. 2006 Apr;16(2):51-52.
Case-control and combined family trios analysis of three polymorphisms in the ghrelin gene in European patients with anorexia and bulimia nervosa.
Cellini E, Nacmias B, Brecelj-Anderluh M, Badia-Casanovas A, Bellodi L, Boni C, Di Bella D, Estivill X, Fernandez-Aranda F, Foulon C, Friedel S, Gabrovsek M, Gorwood P, Gratacos M, Guelfi J, Hebebrand J, Hinney A, Holliday J, Hu X, Karwautz A, Kipman A, Komel R, Rotella CM, Ribases M, Ricca V, Romo L, Tomori M, Treasure J, Wagner G, Collier DA, Sorbi S; EC Framework V 'Factors in Healthy Eating' consortium coordinated by Janet Treasure and David Collier.

J Psychosom Res 2005, 59: 65-72
Grylli V, Wagner G, Hafferl-Gattermayer A, Schober E, Karwautz A.
Disturbed eating attitudes, coping styles, and subjective quality of life in adolescents with type 1 diabetes.

Objectives: To evaluate coping styles and quality of life in youth with Type 1 diabetes with and without eating disorders and to identify relationships between these variables in each group. Methods: Adolescents were evaluated for eating disorders with a two-stage diagnostic procedure. Adolescents with and without eating disorders then provided data on coping styles and on subjective well-being. Results: Adolescents with Type 1 diabetes and disordered eating behavior reported more often blaming themselves and resorting to wishful thinking and poorer physical and psychosocial quality of life than do adolescents with Type 1 diabetes without disordered eating behavior. Specific coping strategies were also positively linked with quality of life and metabolic control. Conclusions: Eating disorders and disordered eating behavior in adolescents with Type 1 diabetes seem to be associated with certain negative and avoidant coping strategies and with impeded physical and biopsychosocial well-being.

 

Eur J Hum Genet. 2005 Apr;13(4):428-34.
Association of BDNF with restricting anorexia nervosa and minimum body mass index: a family-based association study of eight European populations.
Ribases M, Gratacos M, Fernandez-Aranda F, Bellodi L, Boni C, Anderluh M, Cristina Cavallini M, Cellini E, Di Bella D, Erzegovesi S, Foulon C, Gabrovsek M, Gorwood P, Hebebrand J, Hinney A, Holliday J, Hu X, Karwautz A, Kipman A, Komel R, Nacmias B, Remschmidt H, Ricca V, Sorbi S, Tomori M, Wagner G, Treasure J, Collier DA, Estivill X.

Eating disorders (ED), such as anorexia nervosa (AN) and bulimia nervosa (BN), are complex psychiatric disorders where different genetic and environmental factors are involved. Several lines of evidence support that brain-derived neurotrophic factor (BDNF) plays an essential role in eating behaviour and that alterations on this neurotrophic system participates in the susceptibility to both AN and BN. Accordingly, intraventricular administration of BDNF in rats determines food starvation and body weight loss, while BDNF or its specific receptor NTRK2 knockout mice develop obesity and hyperphagia. Case-control studies also suggest a BDNF contribution in the aetiology of ED: we have previously reported a strong association between the Met66 variant within the BDNF gene, restricting AN (ANR) and minimum body mass index (minBMI) in a Spanish sample, and a positive association between the Val66Met and -270C/T BDNF SNPs and ED in six different European populations. To replicate these results, avoiding population stratification effects, we recruited 453 ED trios from eight European centres and performed a family-based association study. Both haplotype relative risk (HRR) and haplotype-based haplotype relative risk (HHRR) methods showed a positive association between the Met66 allele and ANR. Consistently, we also observed an effect of the Met66 variant on low minBMI and a preferential transmission of the -270C/Met66 haplotype to the affected ANR offspring. These results support the involvement of BDNF in eating behaviour and further suggest  its participation in the genetic susceptibility to ED, mainly ANR and low  minBMI.

 

J Pediatr Psychol. 2005 Mar; 30(2):197-206.
Eating disorders and eating problems among adolescents with type 1 diabetes: exploring relationships with temperament and character.
Grylli V, Hafferl-Gattermayer A, Wagner G, Schober E, Karwautz A.

OBJECTIVE: To determine temperament and character among adolescents with type 1 diabetes with and without disordered eating.
METHOD: A clinical sample of 199 adolescents from multiple centers with a mean age of 14.1 (SD, 2.5) years were screened and diagnosed for eating disorders. Assessed were temperament and character as conceptualized by Cloninger, glycemic control, and depression.
RESULTS: Adolescent patients with clinical eating disorders or subthreshold eating problems had significantly higher mean scores in harm avoidance and lower mean scores in self-directedness. Harm avoidance remained significant even after controlling for depressive pathology. DISCUSSION: This study is the first to show evidence that among youths (in particular, girls) with type 1 diabetes,  there is an association between low self-directedness, high harm avoidance, and  the presence of eating, weight, and shape pathology. For these particular  youths, important implications for clinical practice are outlined.

 

Human Molecular Genetics 2004 Apr 28  [Epub ahead of print] 
Association of BDNF with Anorexia, Bulimia and age of onset of weight loss in

six European populations. 

Ribases M, Gratacos M, Fernandez-Aranda F, Bellodi L, Boni C, Anderluh M,

Cavallini MC, Cellini E, Bella DD, Erzegovesi S, Foulon C, Gabrovsek M, Gorwood

P, Hebebrand J, Hinney A, Holliday J, Hu X, Karwautz A, Kipman A, Komel R,

Nacmias B, Remschmidt H, Ricca V, Sorbi S, Wagner G, Treasure J, Collier DA,

Estivill X.

Several genes with an essential role in the regulation of eating behavior and body weight are considered candidates to participate in eating disorders (ED), but no relevant susceptibility genes with a major effect on anorexia (AN) or bulimia (BN) have been identified. Brain-derived neurotrophic factor (BDNF) has been implicated in the regulation of food intake and body weight in rodents. We previously reported a strong association of the Met66 allele of the Val66Met BDNF variant with restricting AN (ANR) and low minimum body mass index (minBMI) in Spanish patients. Another single nucleotide polymorphism (SNP) located in the promoter region of the BDNF gene (-270C/T) showed lack of association with any ED phenotype. In order to replicate these findings in a larger sample, we performed a case-control study in 1142 Caucasian patients with ED consecutively recruited in six different centers from five European countries (France, Germany, Italy, Spain and United Kingdom) participating in the "Factors in Healthy Eating" project. We have found that the Met66 variant is strongly associated to all ED subtypes (AN, ANR, binge-eating/purging AN (ANP) and BN), and that the -270C BDNF variant has an effect on BN and late age at onset of weight loss. These are the first two variants associated to the pathophysiology of ED in different populations and support a role of BDNF in the susceptibility to aberrant eating behaviors.
 

Wiener Klinische Wochenschrift 2004 116/7–8: 230–234
Prevalence and clinical manifestations of eating disorders in Austrian adolescents with type-1 diabetes
Vasileia Grylli, Andrea Hafferl-Gattermayer, Edith Schober, Andreas Karwautz

Objectives: To investigate prevalence and clinical manifestations of DSM-IV clinical eating disorders and subsyndromal eating problems among adolescents with type-1 diabetes.
Method: A clinical sample of 251 adolescents with type-1 diabetes was recruited from multiple centres. Of these adolescents, 199 (96 girls and 103 boys – 79.3% participation rate) with a mean age of 14.1 years (SD: 2.6) were screened for eating disorders and then underwent DSM-IV-based clinical assessment of eating disorders by interview.
Results: 11.5% of the girls and none of the boys with type-1 diabetes had DSM-IV eating disorders, whereas 13.5% of the girls and 1% of the boys had subsyndromal problems of eating and shape. Girls with both type-1 diabetes and a clinical or subclinical eating disorder had a significantly higher body-mass index than those without eating problems.
Conclusion: This Austrian study supports cumulative international evidence that among youths with type-1 diabetes, adolescent girls and especially those having a higher body mass are particularly vulnerable for manifesting pathology of eating, weight and shape. Thus, this particular population requires screening of eating behaviour and relevant psychopathology, close monitoring, and psychosocial interventions through cooperative efforts of specialised centres.

American Journal of Medical Genetics, Neuropsychiatric Genetics, 2004, 124B: 68-72

Combined family trio and case-control analysis of the COMT Val158Met polymorphism in European patients with anorexia nervosa.
Gabrovsek M, Brecelj-Anderluh M, Bellodi L, Cellini E, Di Bella D, Estivill X, Fernandez-Aranda F, Freeman B, Geller F, Gratacos M, Haigh R, Hebebrand J, Hinney A, Holliday J, Hu X, Karwautz A, Nacmias B, Ribases M, Remschmidt H, Komel R, Sorbi S, Tomori M, Treasure J, Wagner G, Zhao J, Collier DA.

The high activity Val158 (H) allele of the dopamine-metabolizing enzyme catechol-O-methyltransferase (COMT) was associated with anorexia nervosa (AN) in a recent family trio-based study of patients from Israel. In an attempt to replicate this finding, we performed a combined family trio and case-control study in an European population from seven centers in six different countries (Austria, Germany, Great Britain, Italy [Milan], Italy [Florence], Slovenia, and Spain), together contributing a total of 372 family trios, 684 controls and 266 cases. TDT analyses of high (H) and low (L) alleles in family trios showed that H allele and L allele were each transmitted 101 times (chi(2) = 0, ns). Allele-wise case-control analysis using separate samples simply combined from the centers was also not significant, with the frequencies of the H allele 50% in cases and same in controls. Stratified analysis of data from all centers gave an odds ratio of 0.98 (Cornfield 95% confidence limits 0.78-1.24). Analysis by genotype was likewise not significant (overall chi(2) = 0.42). Because we were not able to support the primary hypothesis that Val158Met is a risk factor for AN, we did not perform secondary analysis of minimum body mass index (mBMI), age at onset or illness subtype (restricting or binge purging anorexia). Overall we found no support for the hypothesis that the Val158 allele of COMT gene is associated with AN in our combined European sample.
 

Eating & Weight Disorders 2003; 8: 88-94
Eating disorders and type 1 diabetes mellitus in adolescence
Vasileia Grylli, Andreas Karwautz, Andrea Hafferl-Gattermayer, Edith Schober

One of the main difficulties in managing type 1 diabetes mellitus (T1DM) in the young is nutritional treatment. Studies have shown that adolescents (particularly adolescent girls and young women) have an increased risk for clinical and sub-clinical eating disorders. Adjustment to the nutritional regimen and, consequently, to the management of the disease in adolescence seems to involve a complex interplay of various psychosocial and biological aspects. The aim of this review is to consider the relationship between T1DM and eating disorders in adolescence in the light of some important biological, psychological and familial factors. Further research is required in order to detect the degree of the interactions between these factors in adolescents with T1DM.

European Child & Adolescent Psychiatry 2003; 12 (3) 128-135
Perceptions of family relationships in adolescents with anorexia nervosa and their unaffected sisters
Andreas Karwautz, Gerald Nobis, Maria Haidvogl, Gudrun Wagner, Andrea Hafferl-Gattermayer, Cicek Wöber-Bingöl, Max H. Friedrich

The family relationships of patients with anorexia nervosa (AN) have been extensively studied over recent years. However, using case-control designs with unrelated controls is subject to various cultural and familial biases. Studying subjective differential perceptions of family relationships in sister-pairs discordant for the disorder may overcome some of these limitations. The aim of the present study was therefore, to investigate subjective perceptions of family environments in a clinically ill sample of female adolescent patients with acute AN and in their healthy sisters using the Subjective Family Image Test. We found significantly lower perceived individual autonomy and higher perceived cohesion in patients compared with their sisters but no difference in perceived emotional connectedness. Lower perceived individual autonomy of the ill children resulted mainly from their relationships with mothers but also in part from their relationships with fathers. This observed pattern might contribute to the maintenance of the disorder and should be addressed in individual and family interventions.

NeuroReport 2003; 14(6):781-783
Association of the 5-HT2c gene with susceptibility and minimum body mass index in anorexia nervosa
X Hu, O Giotakis, T Li, A Karwautz, J Treasure, DA Collier

The association between a non-conservative Cys23Ser in the 5-HT2c gene and anorexia nervosa in females was examined. We used case-controls and family based association analysis in a sample of 118 patients with DSMIV anorexia nervosa, 244 controls and 47 family trios. There was a significant increase in the frequency of the Ser23 allele in the patients by allele (18.8% vs 12.8%; p = 0.026; OR 1.58, 95% CI 1.0-2.4) and genotype (32.2% vs 19.9%; genotype-wise p = 0.027). There was significant correlation between genotype and minimum BMI (r² = 0.056; p = 0.01), indicating that the Ser23 allele has an effect on severity of illness. We performed TDT analysis using a sub-sample of the cases (58) for whom both parents were available and we found an excess transmission of the Ser23 allele (p = 0.05). Our findings are consistent a role for the Ser23 allele of 5-HT2c in mediating susceptibility to and increasing severity of anorexia nervosa.

Personality disorders and personality dimensions in anorexia nervosa.
Karwautz A, Troop NA, Rabe-Hesketh S, Collier DA, Treasure JL.

Information on the relationship between anorexia nervosa (AN) and personality disorders (PDs) and dimensions of temperament and character (measured by the Temperament and Character Inventory [TCI; Cloninger, Przybeck Svrakic, & Wetzel, 1994]) is limited. This study examines the predictive validity of the TCI for PD diagnoses assessed by the International Personality Disorder Examination-ICD-10 (IPDE-ICD-10; Loranger, Janca, & Sartorius, 1997) interviews of 46 women with DSM-IV-defined AN. Patients with a PD reported higher levels of harm-avoidance and lower levels of self-directedness than those without a PD. Scores on the TCI were predictive of the number of PD features present, particularly for those PDs in the anankastic, anxious, and dependent groups accounting for 40% to 51% of the variance. Cluster analysis based on scores on the TCI identified a subgroup of patients characterized by low levels of novelty seeking, self-directedness, and cooperativeness and high levels of harm avoidance. This cluster included the majority of those with avoidant, anxious, or dependent PDs. Assessment of particular personality dimensions was able to predict PDs in an anorexic sample. Since normal personality dimensions have greater validity than the categorical PDs, a consideration of normal temperament and character may assist in clinical decisionmaking and considerations concerning treatment.

Z Kinder Jugendpsychiatr Psychother 2002 Nov;30(4):251-9 
Subjektives Familienbild bei Anorexia nervosa und Bulimia nervosa im Jugendalter
Karwautz A, Haidvogl M, Wagner G, Nobis G, Wober-Bingol C, Friedrich MH.

OBJECTIVES: The family environments of patients with eating disorders have been studied extensively in recent decades. The "Subjective Family Image Test" is an instrument developed especially to measure differential perceptions by family members. Assessments of subjective family image in families of adolescents by means of this test have been carried out in only a few samples. METHODS: We
aimed first to investigate subjective perceptions by adolescents of their family relations in a larger clinical sample of female adolescents (n = 118) suffering from anorexia nervosa of either subtype or from bulimia nervosa and to compare these perceptions with those of healthy controls (n = 96). Second we investigated intra-familial differences in perception. RESULTS: The main findings were that bulimia nervosa patients perceived lower individual autonomy
and lower emotional connectedness than all other groups, the adolescents with bulimia perceived significantly lower autonomy and emotional connectedness within the family than their fathers, and the restrictive anorexia nervosa patients perceived higher connectedness than their fathers. The relevance of these findings for understanding family dynamics are discussed.
 

Mol Psychiatry 2002;7(7):814 
Analysis of microsatellite markers at the UCP2/UCP3 locus on chromosome 11q13 in anorexia nervosa.
Hu X, Murphy F, Karwautz A, Li T, Giotakis O, Treasure J, Collier DA.

Notes that D. A. Campbell et al. (1999) reported allelic association between a microsatellite marker at the UCP2/UCP3 locus on chromosome 11q13 and anorexia nervosa (AN). They found that one allele (termed allele 13) of the marker D11S911 was over-represented in patients with AN compared to controls, and hypothesized that this may reflect differences in metabolic rate, as determined by variants in either the UCP2 or UCP3 genes nearby. The present study attempted to replicate this finding by analyzing this microsatellite marker, and the nearby D11S916, which Campbell et al also genotyped in their sample. The authors analyzed a sample of 139 white British female patients from SE England with AN and 208 mixed-sex controls. The markers D11S911 and D11S916 were analyzed according to standard florescent genotyping protocols on an AB1377 DNA sequencer/genotyper and allele sizes scored using the GS500 size marker. The authors found no evidence for association between either of the microsatellite markers D11S916 and D11S911 and AN. It is concluded that these markers are not in linkage disequilibrium with a polymorphism which confers susceptibility to anorexia. 
 

European-Eating-Disorders-Review. 2002 Jul-Aug; Vol 10(4): 255-270
Pre-morbid psychiatric morbidity, comorbidity and personality in patients with anorexia nervosa compared to their healthy sisters.
Karwautz,-Andreas; Rabe-Hesketh,-Sophia; Collier,-David-A; Treasure,-Janet-L

Anorexia nervosa (AN) has been linked with pre-morbid disorders, comorbidity, and specific personality traits in between-family case-control studies. However, these findings have not been replicated in within-family studies, and it is not known whether these factors are linked specifically with AN or are shared familial factors. The authors aimed to compare pre-morbid disorders, comorbidity, and specific personality traits between sister-pairs discordant for AN. Forty-five families with two sisters discordant for AN were retrospectively assessed by interview and questionnaires. The proband with AN had mood disorders and personality disorders (PDs) more frequently than their sister and had lower scores of novelty seeking, self-directedness and cooperativeness, and higher scores of harm avoidance, persistence, self-transcendence and of all Eating Disorders Inventory-2 scales. In conclusion, major depression, cluster C PDs, persistence, harm avoidance, and self-transcendence appear to be specific linked to AN and to be individual-specific in nature.
 

Mol Psychiatry 2002;7(3):276-7 
Analysis of microsatellite markers at the UCP2/UCP3 locus on chromosome 11q13 in
anorexia nervosa.
Hu X, Murphy F, Karwautz A, Li T, Freeman B, Franklin D, Giotakis O, Treasure J,
Collier DA.


Mol Psychiatry 2002;7(1):90-4 
The 5-HT(2A) -1438G/A polymorphism in anorexia nervosa: a combined analysis of
316 trios from six European centres.
Gorwood P, Ades J, Bellodi L, Cellini E, Collier DA, Di Bella D, Di Bernardo M,
Estivill X, Fernandez-Aranda F, Gratacos M, Hebebrand J, Hinney A, Hu X,
Karwautz A, Kipman A, Mouren-Simeoni MC, Nacmias B, Ribases M, Remschmidt H,
Ricca V, Rotella CM, Sorbi S, Treasure J; EC Framework V 'Factors in Healthy
Eating' consortium.

Several case-control association studies have raised the possibility that the A
allele of a -1438 G/A polymorphism in the type 2A serotonin receptor (HTR2A)
gene may be a risk factor for anorexia nervosa. However the absence of linkage
and the existence of negative association studies raise the possibility of false
positive findings, resulting from population stratification or lack of
statistical power. To address this controversy we recruited a sample of 316
patients with anorexia nervosa from six European centres, and utilised a
family-based transmission disequilibrium (TDT) approach to analyse the
HTR2A-1438 G/A polymorphism. Age at onset and minimal BMI were also taken into
consideration in order to detect clinical heterogeneity or a quantitative trait
effect. The TDT approach showed that the A allele was transmitted 133 times and
not transmitted 148 times (McNemar chi(2) = 0.29, df = 1, P = 0.59). Also, the
haplotype-based haplotype relative risk method showed no evidence for
association of the A allele, in samples from each centre (chi(2) < 2.15, df = 1,
P > 0.14) and in the total sample (chi(2) = 0.55, df = 1; P = 0.46).
Furthermore, we found no evidence for heterogeneity of the A allele frequency
between samples (chi(2) = 2.54, df = 4, P = 0.64), either according to
minimal-BMI (F1/242 = 2.14, P = 0.45) or age at onset (F1/224 = 2.39; P = 0.12).
QTL-TDT analyses also showed no direct role of the A allele on these traits. We
thus found no evidence for a significant role of the 5-HT(2A) gene in anorexia
nervosa. Previous results may have been exposed to stratification bias (which we
controlled by the TDT method) and/or the risk of type 1 error (from which we
were less exposed because of the sample size).
 

Psychol Med 2001 Feb;31(2):317-29 
Individual-specific risk factors for anorexia nervosa: a pilot study using a
discordant sister-pair design.
Karwautz A, Rabe-Hesketh S, Hu X, Zhao J, Sham P, Collier DA, Treasure JL.

BACKGROUND: The aim of this pilot study was to examine which unique factors
(genetic and environmental) increase the risk for developing anorexia nervosa by
using a case-control design of discordant sister pairs. METHODS: Forty-five
sister-pairs, one of whom had anorexia nervosa and the other did not, were
recruited. Both sisters completed the Oxford Risk Factor Interview for Eating
Disorders and measures for eating disorder traits, and sib-pair differences.
Blood or cheek cell samples were taken for genetic analysis. Statistical power
of the genetic analysis of discordant same-sex siblings was calculated using a
specially written program, DISCORD. RESULTS: The sisters with anorexia nervosa
differed from their healthy sisters in terms of personal vulnerability traits
and exposure to high parental expectations and sexual abuse. Factors within the
dieting risk domain did not differ. However, there was evidence of poor feeding
in childhood. No difference in the distribution of genotypes or alleles of the
DRD4, COMT, the 5HT2A and 5HT2C receptor genes was detected. These results are
preliminary because our calculations indicate that there is insufficient power
to detect the expected effect on risk with this sample size. CONCLUSIONS: A
combination of intrinsic and extrinsic factors increases the risk of developing
anorexia nervosa. It would, therefore, be informative to undertake a larger
study to examine in more detail the unique genetic and environmental factors
that are associated with various forms of eating disorders.


Br J Med Psychol 2001 Mar;74 Part 1:101-114 
Characteristics of self-regulation in adolescent patients with anorexia nervosa.
Karwautz A, Volkl-Kernstock S, Nobis G, Kalchmayr G, Hafferl-Gattermayer A,
Wober-Bingol C C, Friedrich MH.

The purpose of the study was to investigate the different modes of
self-regulation in adolescent anorexia nervosa (AN). A self-system
questionnaire, the Narcissism Inventory, was given to 61 adolescent females with
AN and 61 controls. Patients with AN reported higher overall disturbances in
self-regulation than controls. In particular, a highly unstable self-system, a
tendency to use idealization as modus of regulation, and high narcissistic gain
from their illness was found in the patient group; however, the patients did not
report a 'classic narcissistic sellf'. Furthermore, we were able to
differentiate between two clusters of patients, one with high (n = 34) and one
with low (n = 27) disturbance in self-regulation; the latter reported a shorter
duration of illness and lower oral control but did not differ on any other
clinical variables. Stronger relationships were found between the dimension
'endangered self' and the overall scores of the Eating Attitudes Test (EAT) and
the Eating Disorder Inventory (EDI) as well as two subscales of the EAT and five
of the EDI. Our study in anorexic adolescents demonstrated that the self-system
is experienced as highly unstable, that idealization is used as mode of
regulation, and that the dimension of the 'classic narcissistic self' is less
important in this patient group. It is important to evaluate the system of
self-regulation for planning treatment in the individual patient according to
their needs.
 

Am J Psychiatry 1999 May;156(5):797 
Addition of naltrexone to fluoxetine in the treatment of binge eating disorder.
Neumeister A, Winkler A, Wober-Bingol C.


Int J Eat Disord 1999 Apr;25(3):353-5 
Patulous eustachian tube in a case of adolescent anorexia nervosa.
Karwautz A, Hafferl A, Ungar D, Sailer H.

Autophonia, the hyperperception of one's own voice and breathing, is one of the
consequences of rapid weight loss and is explained within the syndrome of the
patulous eustachian tube. We report on a female adolescent, who presented to an
otologist for autophonia and was finally diagnosed with anorexia nervosa. The
occurrence and relevance of this symptom in eating-disorder patients is
discussed.

Psychotherapeut. 1996; 41(5): 275-287
Therapie von Essstoerungen: Ueberblick ueber Befunde kontrollierter Psycho- und Pharmakotherapiestudien. Treatment of eating disorders: Review of the results of controlled psychotherapy and drug therapy evaluation studies
de-Zwaan,-Martina; Karwautz,-Andreas; Strnad,-Alexandra

In einem Literaturueberblick wird ueber die psychotherapeutischen und pharmakologischen Behandlungsstrategien bei Anorexia und Bulimia nervosa informiert. Besonders hervorgehoben werden dabei die vorhandenen kontrollierten Therapiestudien. Psychotherapie stellt bei beiden Essstoerungen die Therapie erster Wahl dar. Meist werden Behandlungspakete angeboten, die versuchen, der Komplexitaet der Stoerungen gerecht zu werden. Bei der Bulimia nervosa sind die Kurz- und Langzeiterfolge vor allem der kognitiven Verhaltenstherapie, in letzter Zeit auch der interpersonellen Psychotherapie, gut abesichert. Medikamentoese Therapie mit Antidepressiva gilt als Methode zweiter Wahl. Neuere Untersuchungen sprechen fuer ein stufenweises Vorgehen, wobei niederschwellige Therapien, etwa Selbsthilfemanuale, einen ersten Zugang darstellen koennen. Bei der Anorexia nervosa gibt es nur wenige kontrollierte Studien. Operante Methoden zur Gewichtsrestitution gelten heute als unverzichtbarer Bestandteil der ambulanten und der stationaeren Therapie. Familientherapeutische, kognitiv-verhaltenstherapeutische und psychodynamische Therapieverfahren haben sich in der Praxis bewaehrt, sind aber bisher nur ungenuegend durch kontrollierte Studien evaluiert. Von einer routinemaessigen medikamentoesen Therapie der Anorexia nervosa muss beim derzeitigen Kenntnisstand abgeraten werden. 


Klin Padiatr 1988 Jul-Aug;200(4):316-20 
Anorexia nervosa in male adolescents. II. Psychoneuroendocrinologic findings
Toifl K, Waldhauser F, Lischka A, Frisch H.

Female patients with anorexia nervosa (a.n.) are characterized by distinct
endocrine features probably due to hypothalamic pituitary dysfunctions. There is
only a limited number of case reports available on patients with a.n.; mostly
with few data on hormones. In six male patients with a.n. we examined basal and
stimulation values of several hormones performing three pituitary function
tests. Basal and stimulated values of luteinizing hormone (LH) and of follicle
stimulating hormone (FSH) after LHRH were low comparable to results in
prepuberal boys. Similarly, testosterone levels in serum were also markedly
reduced. By exploring the pituitary-thyroidal axis total T4 was diminished in
one patient and at the lower limit in two patients; concentration of free T4 was
in the normal range, while five of six subjects had reduced total T3
concentration and two of six patients showed increased reversed T3 levels; TBG
concentration was always in the normal range. Basal TSH was normal, while in two
patients the TSH stimulation levels after TRH were diminished; in all patients
the TSH stimulation levels were found to be delayed. The basal levels of growth
hormone were normal, but the growth hormone response after insulin was
diminished in four patients. In all six patients basal prolactin (PRL) and PRL
concentration after TRH stimulation was in the normal range. The neuroendocrine
results in the six patients with a.n. confirm in males a similar
hypothalamic-pituitary dysfunction as it is already known for female patients.

Klin Padiatr 1988 Mar-Apr;200(2):113-9 
Anorexia nervosa in male adolescents. I: Clinical findings
Toifl K, Lischka A, Waldhauser F.

In six male patients with anorexia nervosa (a.n.) we describe the anamnestic
data, the course of disease and progress in therapy. We also present the results
of psychological testing and organic investigations. The mean weight loss at the
time of first investigation at the clinic was 70% of ideal body weight. The mean
time between first symptoms of a.n. and the first admission at the clinic was 19
months. The psychopathological status showed in all six patients symptoms of
obsessive, in two patients additional of depressive behavior. This finding is in
contradiction to the result in 61 female patients with a.n., where hysteriformic
and depressive symptoms predominated (36). The follow up time reached from 18 to
84 months (mean 49 months). At the time of last control-investigation we found
only one patient restored to health, two patients showed a positive progression.
In two patient the psychiatric situation was nearly unchanged, one patient
committed suicide. The three patients without positive therapeutic effect were
three times respectively six times at the inpatient department and discontinued
two times or also three times the psychotherapy. In our experience the course of
disease in male patients with a.n. seems to be more serious and more resistant
to therapy than in female patients.

Wien Klin Wochenschr 1986 Jun 13;98(12):393-7 
Basal gonadotropin level and gonadotropin response to stimulation in patients
with anorexia nervosa
Waldhauser F, Toifl K, Spona J, Frisch H.

Serum gonadotropin (GN) levels were examined before and after stimulation with
luteinizing-hormone-releasing-hormone (LHRH) (100 micrograms/m2 body surface) in
25 female patients with anorexia nervosa (AN) and in 19 healthy young women. 12
patients were reexamined after clinical improvement. Basal GN levels and the
luteinizing hormone (LH) response to stimulation were significantly lower in
patients than in controls, whereas the response of follicle-stimulating hormone
(FSH) to LHRH was normal. The GN response in patients was weight dependent,
displaying an inverse correlation to the weight loss. After clinical improvement
the GN response was significantly higher than in the acute stage of the disease.
The data demonstrate that the activity of the hypothalamic-hypophyseal-gonadal
(H-H-G) axis, evaluated on the basis of the GN response to LHRH, depends on the
body weight of the patient. Hence, the alteration in activity of the H-H-G axis
seems to be a consequence, and not the cause of AN.

Z Kinder Jugendpsychiatr 1985;13(2):110-22 
Anorexia-nervosa--psychopathologic findings in relation to body weight and
neuroendocrinologic changes
Toifl K, Friedrich MH, Waldhauser F.

The present study was conducted to investigate the relationship of
psychopathological, behavioral and neuroendocrinological variables to weight
profiles in patients with anorexia nervosa. The subjects were 67 patients with
anorexia nervosa (61 females, 6 males). Eighteen (27%) were found to have a
diffuse organic brain syndrome. Symptoms of hysterical and depressive neurosis
predominated among the female subjects and those of obsessive-compulsive
neurosis among the male subjects. Obsessive-compulsive and depressive traits
were seen more frequently in the subjects with organic brain syndrome (14 of 18)
than in the other subjects. One third of the female subjects showed resistance
during therapy. Neuroendocrinological investigations (LHRH and TRH tests) were
carried out on 27 of the female subjects. The stimulation values for the
hormones LH, FSH, TSH and prolactin showed a significant dependence on weight.
The symptomatology found in the subjects with organic brain syndrome largely
parallels that of the psycho-organic hunger syndrome described by Baeyer.
Correlations were found between weight loss and both blood chemistry findings
and changes in psychosocial behavior.

J Clin Endocrinol Metab 1984 Sep;59(3):538-41 
Diminished prolactin response to thyrotropin and insulin in anorexia nervosa.
Waldhauser F, Toifl K, Spona J, Zeitlhuber U, Waldhauser M, Frisch H.

Although patients with anorexia nervosa (AN) have a variety of endocrine
disturbances, it generally is believed that the PRL response to stimulation is
not altered in this disorder. We measured basal serum PRL values and serum PRL
values after stimulation either with TRH (200 micrograms/m2) or with insulin (4
IU/m2) in 27 women with AN and 9 normal women. Basal values in anorexic women
and normal women did not differ significantly, whereas all stimulation variables
(mean PRL stimulation values, maximum PRL values, sum of increments, and area
under the stimulation curve) were significantly lower in AN patients than in
normal women. Furthermore, after TRH stimulation most of these variables
correlated positively with the percentage of ideal body wt of the patients,
indicating that the diminished PRL response was wt dependent. This diminished
PRL response in the patients may accompany starvation and low estradiol values.
Both conditions per se are known for their association with diminished PRL
responses. Hence, no hypothesis which posits hypothalamic dopamine excess as the
basic disturbance in AN seems justified. Moreover, diminished PRL responses in
AN are not consistent with an assumption of hypothalamic dopamine depletion in
this disorder.

Clin Chim Acta 1982 Aug 4;123(1-2):27-32 
Excretion of biogenic amine metabolites in anorexia nervosa.
Riederer P, Toifl K, Kruzik P.

Urinary metabolites of catecholamines and indoleamines have been investigated in
16 patients with anorexia nervosa (AN) and 13 controls using a HPLC-method.
Vanillic mandelic acid, 3-methoxy-4-hydroxyphenylglycol, homovanillic acid,
3,4-dihydroxyphenylacetic acid, 5-hydroxyindole acetic acid and indoleacetic
acid were significantly decreased in the pre-treatment phase. In four patients
long-term treatment including parenteral and enteral nutrition together with
psychological methods resulted in an increase in the levels of these substances
and this correlated with increased weight gain and urinary creatinine. It is
concluded that both central and peripheral disturbances are involved in AN,
particularly with regard to biogenic amine metabolism.

Padiatr Padol 1981;16(3):353-62 
Research in family dynamics with anorexia nervosa
Friedrich MH.

33 anorectic patients between the ages of 9 and 18 were treated from 1975 and
1980 as in-patients at the University clinic of neuro-psychiatry for children
and juveniles. Familial criteria such as personal relationships; role allocation
according to the Richter system and family structure were used as parameters.
Sequence of siblings, age of parents and social factors were also taken into
consideration.

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