Evidence for the role of EPHX2 gene variants in anorexia nervosa.

Anorexia nervosa (AN) and related eating disorders are complex, multifactorial neuropsychiatric conditions with likely rare and common genetic and environmental determinants. To identify genetic variants associated with AN, we pursued a series of sequencing and genotyping studies focusing on the coding regions and upstream sequence of 152 candidate genes in a total of 1205 AN cases and 1948 controls. We identified individual variant associations in the Estrogen Receptor-ß (ESR2) gene, as well as a set of rare and common variants in the Epoxide Hydrolase 2 (EPHX2) gene, in an initial sequencing study of 261 early-onset severe AN cases and 73 controls (P=0.0004). The association of EPHX2 variants was further delineated in: (1) a pooling-based replication study involving an additional 500 AN patients and 500 controls (replication set P=0.00000016); (2) single-locus studies in a cohort of 386 previously genotyped broadly defined AN cases and 295 female population controls from the Bogalusa Heart Study (BHS) and a cohort of 58 individuals with self-reported eating disturbances and 851 controls (combined smallest single locus P<0.01). As EPHX2 is known to influence cholesterol metabolism, and AN is often associated with elevated cholesterol levels, we also investigated the association of EPHX2 variants and longitudinal body mass index (BMI) and cholesterol in BHS female and male subjects (N=229) and found evidence for a modifying effect of a subset of variants on the relationship between cholesterol and BMI (P<0.01). These findings suggest a novel association of gene variants within EPHX2 to susceptibility to AN and provide a foundation for future study of this important yet poorly understood condition.

[Internet-based approaches in the therapy of eating disorders]. / Internetbasierte Ansätze in der Therapie von Essstörungen.

Recent technological developments of communication media offer new approaches to diagnostic and therapeutic interactions with patients. One major development is Internet-based primary prevention in vulnerable individuals not yet suffering as well as the development of new therapeutic approaches for affected individuals based on the experiences of guided self-help through CD, DVD or bibliotherapy. The eating disorder literature shows several interesting, partly controlled and randomized, studies on bulimia nervosa, a few studies on binge eating disorder and no studies on anorexia nervosa. As part of the German Eating Disorder Network on Psychotherapy (EDNET) a 9-month Internet-based relapse prevention program for patients with anorexia nervosa after inpatient treatment was evaluated. Conception, first experiences and first results of the Internet-based relapse prevention program for anorexia nervosa are reported.

Is season of birth related to disordered eating and personality in women with eating disorders?

We assessed the relation between season of birth and eating disorder symptoms and personality characteristics in a sample of 880 women with eating disorders and 580 controls from two Price Foundation Studies. Eating disorder symptoms were assessed using the Structured Interview of Anorexic and Bulimic Disorders and the Structured Clinical Interview for DSM-IV. Personality traits were assessed using the Temperament and Character Inventory and the Frost Multidimensional Perfectionism Scale. Date of birth was obtained from a sociodemographic questionnaire. No significant differences were observed 1) in season of birth across eating disorder subtypes and controls; nor 2) for any clinical or personality variables and season of birth. We found no evidence of season of birth variation in eating disorders symptoms or personality traits. Contributing to previous conflicting findings, the present results do not support a season of birth hypothesis for eating disorders.

Twenty-five-year course and outcome in anxiety and depression in the Upper Bavarian Longitudinal Community Study.

OBJECTIVE: Assessment of 25-year course of pure and mixed anxiety and depression in a community sample. METHOD: Participants were grouped into pure anxiety, pure depression, mixed anxiety and depression, and no anxiety or depressive syndrome at baseline. Assessments consisted of a: i) baseline survey, ii) 5-year follow-up, iii) 25-year follow-up. Self-rating scales as well as expert-rating interviews yielded data on social and psychopathological risk factors and outcome measures. RESULTS: Baseline prevalence for mixed anxiety and depressive syndrome was 8.7%. Subjects with combined anxiety and depressive syndrome were more predisposed towards later adverse mental health outcomes and reduced functionality. The transition from anxiety syndrome (pure and mixed) to depressive syndrome over the 25-year study is more likely than the reverse. Logistic regression analysis emphasized the impact of early anxiety syndromes on later depression. CONCLUSION: Results underscore the long-term risks of suffering from a combined anxiety and depressive syndrome.

Anorexia nervosa trios: behavioral profiles of individuals with anorexia nervosa and their parents.

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 (approximately 33%) comprised low symptom probands and mothers with scores in the healthy range. Class 2 ( approximately 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 (approximately 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.

Intervention effects of supplying homeless individuals with permanent housing: a 3-year prospective study.

OBJECTIVE: To describe the intervention effects of supplying homeless individuals with permanent housing. METHOD: In a prospective study, 109 male and 20 female homeless individuals were assessed at baseline and at 1- and 3-year follow-up concerning mental illness (SCID-I), psychopathology, global assessment of functioning, emotional lability and alcohol consumption. RESULTS: A high proportion (86%) of the individuals was able to maintain or improve stability of housing. Only minor changes were observed concerning mental illness and global functioning. Extensive alcohol consumption and high psychopathology increased the risk of losing the stable housing. CONCLUSION: The placement of homeless individuals in board and care homes or community housing after social counselling seems to be a necessary measure to remedy homelessness. However, supplying more permanent housing is not sufficient to decisively improve mental health status.

[Anorexic and bulimic eating disorders]. / Anorektische und bulimische Essstörungen.

Anorexic and bulimic eating disorders today are rather frequent in adolescent girls and young women of developed industrial countries. News media frequently report such patients, and lay people are interested. For scientists, it is not easy to explain the etiology and pathophysiology of these eating disorders. Clinically, treatment is a challenge. General risk factors for the development of anorexic and bulimic eating disorders are (1) female gender, (2) adolescence, and (3) living in an industrial country. Special risk factors are (1) obesity or mental disorders (eating, depression, substance use), (2) premorbid characteristics (early menarche, childhood obesity, anxiety disorder, low self-esteem, and perfectionism), and (3) premorbid stresses. Biological and sociocultural factors and personally threatening experiences all play a role in the etiology. Especially in early phases of the illness, affected patients do not appear to suffer, are reluctant to admit symptoms, and may avoid necessary treatment. Progress has recently been made in the understanding and treatment of anorexic and bulimic eating disorders.

[Effects and cost-effectiveness analysis of inpatient treatment for somatoform disorders]. / Wirksamkeit und Kosten-Nutzen-Effekte der stationären Therapie somatoformer Störungen.

Patients with somatoform disorders represent an expensive problem group of the healthcare system characterized by inappropriately high medical costs. This paper describes a controlled inpatient treatment study using a cognitive-behavioral approach. The aim of this treatment program was to improve the patients' symptomatology and their psychosocial functioning, as well as reducing unnecessary medical costs. We treated 172 patients with somatoform disorders (DSM-IV) and compared them with 262 patients of a waiting control list. An additional control group consisted of 123 patients with other mental disorders. Direct and indirect illness-related costs for the two-year periods before and after treatment were re-calculated using objective data provided by the health insurance companies. The results show a marked improvement in the areas of bodily complaints, health anxieties, dysfunctional beliefs towards body and health, depression and psychosocial impairments. The medical costs in the post-treatment period decreased by 1,098 euro (-36.7 %) for inpatient and 382 euro (-24.5 %) for outpatient treatments. Indirect costs due to days lost from work were 6,702 euro (-35.3 %) lower than during the two-years before treatment. The treatment costs had amortized after 21.5 months. We identified a subgroup of high-utilizing somatoform patients for which per patient savings of 32,174 euro (-63.9 %) were found. These results confirm that the cognitive-behavioral approach is effective in improving complaints as well as reducing the health-economical burden of somatoform disorders.

Expressed emotion, family environment, and parental bonding in bulimia nervosa: a 6-year investigation.

As part of a prospective, long-term treatment study, 30 in-patients with bulimia nervosa (BN) were divided into groups with high and low expressed emotion (EE) family backgrounds according to the Camberwell Family Interview, and followed for a period of six years. The high EE group initially showed significantly more psychopathology than the low EE group. No group x time interactions were found, but the high EE group showed a worse outcome on the "conflict" and "organisation" subscales of the Family Environment Scale. They also showed significantly more eating disorder pathology according to the Eating Disorder Inventory (EDI) and the Structured Interview for anorexia nervosa (AN) and BN before treatment at discharge, after two years and, to some degree, even after six years. Depth of depression (Beck Depression Inventory) was significantly higher in the high EE group at admission (moderate depression), discharge and after the 6-year follow-up (still slight depression). The Parental Bonding Instrument (PBI) showed no differences between the high EE and low EE groups, but the individuals with "affectionless control" according to the PBI had more negative scores on three of the subscales of the Family Environment Scale (FES). In brief, the high EE individuals with BN were initially sicker and did not fully catch up over time in comparison with the symptomatic recovery of the low EE individuals. These data suggest that EE status upon admission to in-patient treatment is a relevant predictor of the severity and course of BN and depressive symptoms.

Maintenance of weight loss after obesity treatment: is continuous support necessary?

OBJECTIVE: This study examined outcome differences of 109 obese subjects, who participated in a 10-week cognitive-behavioral inpatient treatment followed by either a weight maintenance program or a follow-up period without professional support. METHODS: Self-rated weight loss, eating behaviors, and general psychopathology were assessed several months before treatment, when subjects were admitted, at discharge, and at the 6-, 12-, and 18-month follow-ups. Structured interviews for mental disorders and eating pathology were conducted additionally. RESULTS: The mean weight of the sample at baseline was 127 kg. Weight loss of the total sample amounted to 8.0 kg (6.3%) and was completely maintained during the follow-up period. Significant reductions of eating and general psychopathology were observed at the 18-month follow-up. The outcome in the maintenance condition did not significantly differ from the outcome in the control condition. CONCLUSIONS: Weight regain after obesity treatment is not inevitable, but continuous patient-therapist contacts do not distinctly improve treatment effects.

Dimensional and categorical approaches to hypochondriasis.

BACKGROUND: The DSM-IV definition of hypochondriasis is contrasted with hypochondriacal dimensions as provided by the Whiteley Index (WI) and Illness Attitude Scales (IAS). METHODS: Exploratory factor analysis was conducted on self-report data from 570 patients with mental and psychophysiological disorders. Of these, 319 were additionally diagnosed according to DSM-IV by structured interviews. RESULTS: The three 'classic' factors of the WI labelled disease phobia, somatic symptoms and disease conviction were confirmed. The IAS consisted of two dimensions indicating health anxiety and illness behaviour. The overall scores of both instruments were highly correlated (0.80). Optimal cut-off points for case identification yielded sensitivity/specificity rates of 71/80% (WI) and 72/79% (IAS). The IAS was superior to the WI when patients with hypochondriacal disorder were to be discriminated from non-hypochondriacal somatizers. Largest group differences were found for scales related to affective components (health anxieties), smallest for illness behaviours. Affective components of hypochondriasis explained more variance of diagnostic group membership than somatization symptoms. The subscales of disease phobia (WI) and health anxiety (IAS) were most sensitive to treatment-related changes. CONCLUSIONS: The self-rating scales are valid for screening, case definition and dimensional assessment of hypochondriacal disorder, including the differentiation between hypochondriasis and somatization. The existence of distinguishable affective and cognitive components was confirmed.

Evidence for a susceptibility gene for anorexia nervosa on chromosome 1.

Eating disorders, such as anorexia nervosa (AN), have a significant genetic component. In the current study, a genomewide linkage analysis of 192 families with at least one affected relative pair with AN and related eating disorders, including bulimia nervosa, was performed, resulting in only modest evidence for linkage, with the highest nonparametric linkage (NPL) score, 1.80, at marker D4S2367 on chromosome 4. Since the reduction of sample heterogeneity would increase power to detect linkage, we performed linkage analysis in a subset (n=37) of families in which at least two affected relatives had diagnoses of restricting AN, a clinically defined subtype of AN characterized by severe limitation of food intake without the presence of binge-eating or purging behavior. When we limited the linkage analysis to this clinically more homogeneous subgroup, the highest multipoint NPL score observed was 3.03, at marker D1S3721 on chromosome 1p. The genotyping of additional markers in this region led to a peak multipoint NPL score of 3.45, thereby providing suggestive evidence for the presence of an AN-susceptibility locus on chromosome 1p.

Predictors of post-treatment weight reduction after in-patient behavioral therapy.

OBJECTIVE: The goal of the present study was to identify covariates and predictors of post-treatment weight reduction. To clarify the impact of the individual factors, we compared "winners" (losing more than 2 BMI-points in the follow-up period) with "losers" (gaining more than 2 BMI-points in the same time). DESIGN: In a questionnaire based study, we evaluated the psychological impact on eating behavior, general psychopathology and depressive symptoms at three points in time: three months prior to admission (T0), at the beginning (T1) and at the end of in-patient treatment (T2) as well as 6, 12, and 18 months after treatment (T3-T5). SUBJECTS: One hundred and thirty eight obese patients (BMI<30 kg/m(2)) were recruited to the study. All patients participated in a multimodal in-patient treatment program over a period of 10 weeks. Treatment elements were cognitive behavioral therapy, movement therapy, and nutritional counseling. The aim of treatment was to regulate food intake, to minimize dysfunctional emotional influences on eating behavior, to enhance physical exercise and to treat comorbid psychiatric disorders. Twenty nine patients (13%) of the initial sample dropped out or were excluded during the treatment and post-treatment period. RESULTS: During in-patient treatment eating behavior improved and body weight decreased considerably in all patients. The weight reduction continued slightly in the follow-up period. Moreover, general psychopathology, depressive symptoms and eating behavior improved and remained stable during follow-up. These benefits were closely related to weight reduction. Neither eating behavior, nor eating related cognition nor psychopathology measured at T0 and T1 predicted long term success at T5. "Winners" as compared to "losers" at follow-up showed less psychopathology, less depressive symptoms and a less disturbed eating behavior. Already at discharge (T2), winners were less prone to eating triggered by external stimuli and reported fewer feelings of hunger. These differences predicted post-treatment weight reduction (T3-T5). CONCLUSION: Reported feelings of hunger and the tendency to disinhibited eating behavior measured at discharge were able to predict post-treatment weight reduction in our sample. Patients suffering from a feeling of hunger during in-patient treatment were less likely to show further weight reduction in the follow-up period. Similarly, reduction of "disinhibition" during treatment is a precondition for post-treatment weight loss.

[Diagnosis and treatment of somatoform disorders (functional physical complaints)]. / Diagnostik und Behandlung somatoformer Störungen (funktioneller körperlicher Beschwerden).

In modern classification systems, unexplained physical symptoms without an organic origin are labelled "somatoform disorders". This syndrome is very frequent and causes a lot of treatment costs as well as indirect costs (such as workers' compensation and others). In the past, effective treatment strategies were lacking. However, consideration of modern scientific results has made it possible to develop treatment approaches which find the acceptance of the patients and which are highly effective. A hierarchical approach is presented suggesting the following steps: a) Primary care: The consideration of management rules in primary care can prevent the chronicity of somatoform symptoms. b) Brief psychological and psychopharmacological treatments: Modern cognitive-behavioural approaches can help to cope with the symptoms and to improve the subjective well-being. First results for pharmacological treatments are encouraging. c) Integrative inpatient treatment including intense psychotherapeutic and psychosomatic ingredients. Experts' judgements of course and prognosis in somatoform disorders should consider the following features: Duration and multiplicity of the complaints; comorbidity with other psychiatric and physical disorders; disability in different areas of life such as at work, family, leisure time; individual coping strategies; treatment approaches in the past.

Searching for a gastrointestinal subgroup within the somatoform disorders.

The authors examined whether patients suffering from functional gastrointestinal symptoms constitute a separate group within the broader concept of the somatoform disorders. The authors compared 103 patients with a severe gastrointestinal syndrome, 220 patients with a somatization syndrome according to DSM-IV, and 250 clinical control subjects with nonsomatoform mental disorders. The gastrointestinal group showed more catastrophizing thinking, complained more about autonomic sensations, felt bodily weaker, was less tolerant towards bodily discomfort, had developed more hypochondriacal fears and behaviors, was more depressed, and was more severely disabled in different areas of psychosocial functioning than the other groups. These differences, however, disappeared when general somatization was controlled for by analysis of covariance. Only a small effect related to dysfunctional cognitions remained specific to the gastrointestinal syndrome. Because these results do not confirm the idea of an independent gastrointestinal syndrome, general mechanisms of somatization seem to play the dominant role.

Prevalence of mental illness in homeless men in Munich, Germany: results from a representative sample.

OBJECTIVE: The aim of the study was a reliable assessment of the prevalence of DSM-IV mental disorders in a representative sample of homeless men in the city of Munich. METHOD: A preliminary survey yielded an estimate of 1,022 single homeless men in Munich divided among three sectors (shelter users, service users and street dwellers). A random sample of 265 single homeless men was surveyed from these three sectors. An age-matched comparison group of 178 men was selected randomly from a community register. The Structured Clinical Interview for DSM-IV (SCID-IV) was used for diagnostic classification. RESULTS: The lifetime prevalence rates of mental disorders were as follows: 72.7% vs. 15.2% for alcohol dependence, 32.8% vs. 7.3% for mood disorders, 15.9% vs. 6.2% for anxiety disorders and 9.8% vs. 0.6% for psychotic disorders. Of the homeless males in Munich, 93.2% had at least one lifetime DSM-IV axis I diagnosis, while this was the case for only 38.2% of the community controls. One-month prevalence for all SCID DSM-IV axis I disorders in homeless males was 73.4%. CONCLUSION: Lifetime DSM-IV axis I mental disorders were 2.4 times more frequent among homeless individuals compared to community control. Implications for health care planning are discussed.

Comparing self- and expert rating: a self-report screening version (SIAB-S) of the structured interview for anorexic and bulimic syndromes for DSM-IV and ICD-10 (SIAB-EX).

OBJECTIVE: Carrying out structured interviews in larger numbers by well-trained interviewers is costly and time consuming. Therefore, we developed parallel to the existing Structured Interview for Anorexic and Bulimic Syndromes (SIAB-EX) a similarily designed questionnaire for symptoms of disordered eating and related areas (SIAB-S). METHOD: 377 treated eating disordered patients were assessed within a two-week time period using both the SIAB-EX and SIAB-S. RESULTS: Generally, self-ratings based on the SIAB-S were quite similar to expert ratings. Cohen's kappa showed good agreement between self- and expert ratings. Factor structure based on principal component analyses of expert ratings or self-ratings led to rather similar results confirming the robustness of the subscales in self- and expert ratings. Using expert rating as a criterion, the self-rating (SIAB-S)--which can more easily be used for screening purposes--had a sensitivity of 0.70, a specificity of 0.80 and a PPV = 0.91 for the DSM-IV diagnoses of AN and/or BN (worst ever condition). Diagnostic sensitivity (79/73%) and specificity (66/63 %) were in an acceptable range (past/current). If we focus on the differences between the two approaches the following was found: self-rating (compared to expert-rating) resulted in lower scores for items inquiring about binges and inappropriate compensatory behaviour, attitudes towards food and eating, and social interaction. On the other hand, self-rating (compared to expert-rating) led to higher scores for items measuring general psychopathology and atypical binging. CONCLUSION: Compared to the "gold standard" of t data obtained with investigator-based standardised or structured interviews, data based on self-rating with items formulated clearly and concisely can lead to reliable and valid results. While complex issues (what is a binge) are difficult to assess in self-ratings, some (very personal) questions may even be better asked in a self-report questionnaire.

Temperament and character in women with anorexia nervosa.

The present study examined temperament differences among anorexia nervosa (AN) subtypes and community controls, as well as the effect of body weight on personality traits in women with AN. Temperament and Character Inventory (TCI) scores were compared between 146 women with restrictor-type AN (RAN), 117 women with purging-type AN (PAN), 60 women with binge/purge-type AN (BAN), and 827 community control women (CW) obtained from an archival normative database. Women with AN scored significantly higher on harm avoidance and significantly lower on cooperativeness than CW. Subtype analyses revealed that women with RAN and PAN reported the lowest novelty seeking, RAN women the highest persistence and self-directedness, and PAN women the highest harm avoidance. Body mass index had a nominal effect on subgroup differences, suggesting that personality disturbances are independent of body weight. Findings suggest that certain facets of temperament differ markedly between women with AN, regardless of diagnostic subtype, and controls. More subtle temperament and character differences that were independent of body weight emerged that distinguish among subtypes of AN.

The DSM-IV nosology of chronic pain: a comparison of pain disorder and multiple somatization syndrome.

This study evaluates the classification of pain from the perspective of the DSM-IV system. Of 60 in-patients with long-standing and disabling pain syndromes, 29 with pain disorder (PD) and 31 with pain as part of a multiple somatization syndrome (MSS) were compared before and after a structured cognitive-behavioral treatment. It was hypothesized that MSS patients show more psychological distress, are more severely disabled, and respond less to the treatment. Both groups were similar with respect to sociodemographic status, history of pain symptomatology and comorbidity with DSM-IV mental disorders. The results show that MSS patients had higher levels of affective and sensoric pain sensations as well as more pain-related disabilities. They were also less successful during treatment to reduce their pain-related depression and anxiety. Psychosocial functioning was improved only by PD patients, but remained almost unchanged in the MSS group. However, there were no group differences concerning general depression and hypochondriasis, dysfunctional attitudes towards body and health, and use of pain coping strategies. It is concluded that the DSM-IV distinction between 'pure' pain disorder and syndromes involving pain plus multiple somatoform symptoms cannot generally be confirmed, but further studies of validation are needed.