No association of brain-derived neurotrophic factor Val66Met polymorphism with anorexia nervosa in Japanese.

The Met66 allele of the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene has been reported to be associated with anorexia nervosa (AN), and also lower minimum body mass index (BMI) and higher harm avoidance in AN. We genotyped the Val66Met polymorphism (rs6265) in 689 AN cases and 573 control subjects. There were no significant differences in the genotype or allele frequencies of the Val66Met between AN and control subjects (allele wise, odds ratio = 0.920, 95% CI 0.785-1.079, P = 0.305). No difference was found in minimum BMIs related to Val66Met in AN (one-way ANOVA, P > 0.05). Harm avoidance scores on the Temperament and Character Inventory were lower in the Met66 allele carriers (P = 0.0074) contrary to the previous report. Thus we were unable to replicate the previous findings that the Met66 allele of the BDNF is associated with AN and that the minimum BMI is lower or the harm avoidance score is higher in AN patients with the Met66 allele.

The relationship between the age of onset of type 1 diabetes and the subsequent development of a severe eating disorder by female patients.

OBJECTIVES: To determine the age of onset of type 1 diabetes that is most closely related to the subsequent development of a severe eating disorder such as anorexia nervosa (AN) or bulimia nervosa (BN). METHODS: Participants were 53 female type 1 diabetes patients with AN or BN referred to our outpatient clinic from the Diabetes Center of Tokyo Women's Medical University. Forty-nine female type 1 diabetes patients who regularly visited the Diabetes Center and had no eating disorder-related problems constituted the 'direct control' group, whereas 941 female patients who for the first time visited the Diabetes Center constituted the 'historical control' group. The kernel function method was used to generate a density estimation of the onset age of each group and the chi-square test was used to compare the distribution. RESULTS: The control groups had similar density shapes for the onset age of type 1 diabetes, but both differed from the 'eating disorder' group. For onset age 7-18 yr, the density of the 'eating disorder' group was higher than those of the control groups, but for the younger and older onset ages the densities were lower. The 'eating disorder' group developed type 1 diabetes significantly more frequently than the 'historical control' group between 7 and 18 yr of age (χ2 = 9.066, p < 0.011). CONCLUSION: The development of type 1 diabetes in preadolescence or adolescence seems to place girls at risk for the subsequent development of AN or BN. Careful attention should be paid to these high-risk patients.

BMI, body composition, and the energy requirement for body weight gain in patients with anorexia nervosa.

OBJECTIVE: Theories abound about the energy requirements for body weight gain in anorexia nervosa (AN). We hypothesized that malnutrition status affects the energy requirements. METHOD: On admission, 97 AN patients were measured for body composition by dual-energy X-ray absorptiometry. The relationship between body mass index (BMI) and body composition was investigated. In addition, 21 patients who completed our treatment program were tested for energy intake and body weight. RESULTS: The relationship between BMI and both fat-free mass and fat mass (FM) on admission was curvilinear. The weight gain per excess energy was greater in the group of patients with FM < 4 kg or BMI < 14 kg/m(2) than in the group with FM > or = 4 kg or BMI > or = 14 kg/m(2) (p = .037, p = .055, respectively). DISCUSSION: The energy requirements for weight gain in AN patients are related to the initial FM and BMI.

The duration of severe insulin omission is the factor most closely associated with the microvascular complications of Type 1 diabetic females with clinical eating disorders.

OBJECTIVE: To investigate which features of eating disorders are associated with retinopathy and nephropathy in Type 1 diabetic females with clinical eating disorders. METHOD: Participants were 109 Type 1 diabetic females with clinical eating disorders diagnosed by the structured clinical interview for DSM-IV (bulimia nervosa [n = 70], binge-eating disorder [n = 28], anorexia nervosa [n = 7], and eating disorder not otherwise specified [n = 4]). Retinopathy and nephropathy were screened and demographic, medical, and eating disorder related factors were investigated. To identify the factors associated with each complication, logistic regression analysis was done. RESULTS: Duration of severe insulin omission and duration of Type 1 diabetes were significantly associated with retinopathy (odds ratios = 1.35 and 1.23, respectively) and nephropathy (odds ratio = 1.35 and 1.21, respectively) in multivariate regression analyses. CONCLUSION: Of the various problematic behavioral factors related to eating disorders, the duration of severe insulin omission was the factor most closely associated with the retinopathy and nephropathy of Type 1 diabetic females with clinical eating disorders by multivariate analysis. This finding may help patients who deliberately omit insulin become aware of medical risk of insulin omission.

Classification of type 1 diabetic females with bulimia nervosa into subgroups according to purging behavior.

OBJECTIVE: To classify type 1 diabetic females with bulimia nervosa (BN) by type of inappropriate compensatory behavior in order to prevent weight gain (ICB) and to investigate the group differences. RESEARCH DESIGN AND METHODS: Type 1 diabetic females with BN, diagnosed by structured diagnostic interview based on DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th ed.) criteria, were classified by type of ICB as follows: 1) only severe insulin omission as an ICB (BN-I) (n = 22), 2) both severe insulin omission and self-induced vomiting and/or laxative abuse (BN-IP) (n = 22), or 3) no insulin omission but another ICB (BN-NI) (n = 11). The clinical characteristics of these three groups and a binge-eating disorder (BED) group (n = 24) were compared. RESULTS: The BN-IP and BN-I groups had the highest HbA(1c) levels. The BN-IP group had the highest rates of diabetic neuropathy, retinopathy, and nephropathy. The BN-NI group had the second highest rates of neuropathy and retinopathy. The BN-IP group had the highest frequencies of diabetes- and ketoacidosis-related hospital admissions, and the BN-I group had the second highest frequencies. The BN-NI group showed the highest scores on psychological tests related to depression, anxiety, eating disorder psychopathology, and perfectionism. The BN-NI group had the highest rate of history of visits to a psychiatrist, and the BN-IP group had the second highest history. CONCLUSIONS: Type 1 diabetic females with BN seem not to be homogenous and can be classified into three distinctive subgroups by type of ICB. Individuals with BN-IP had the most severe problems with both medical and psychological/behavioral aspects. Individuals with BN-NI manifested the highest psychological distress. The BN-I group had comparatively mild distress despite having the poorest metabolic control. Each BN group manifested more severe pathology than the BED group.

Three cases of appendicitis with anorexia nervosa under inpatient care.

BACKGROUND: Little is known about the occurrence of appendicitis during the re-nourishment period in anorexia nervosa (AN). We report three cases of appendicitis in patients with AN that occurred after hospitalization for treatment of AN. CASE PRESENTATION: Case 1 is a 34-year-old female, case 2 is a 17-year-old female and case 3 is a 38-year-old female. Constipation was observed in all three cases. Careful management of defecation might be essential to prevent appendicitis among AN patients during the re-nourishment period under inpatient care. In addition, mild and diffuse symptoms were observed in all three cases. Therefore, diagnosis proved to be difficult to make and abdominal computed tomography was particularly helpful in all cases. As the symptoms were diffuse, the condition of appendicitis turned out to be more severe and complicated in one case. Additionally, the incidence of appendicitis in AN in the current study might be higher than that in the normal population. CONCLUSIONS: These findings suggest that appendicitis should be considered as one of the potentially important complications in the therapy for AN.

Aggressive behavior and serum testosterone concentration during the maturation process of male mice: the effects of fetal exposure to bisphenol A.

The relationship between exposure to endocrine-disrupting chemicals (EDs) and risk to reproductive organs is well documented, but the influence of EDs on behavioral development has not been studied. In this study we evaluated the effect of fetal exposure to bisphenol A, which mimics estrogenic activity, on aggressive behavior and hormonal change in male mice. On gestation days 11-17, female mice were fed bisphenol A at 2 ng/g or 20 ng/g of body weight (environmentally relevant concentration). Aggression rating and blood sampling of the offspring were done at 8, 12, and 16 weeks of age. Aggression scores increased significantly (p < 0.01) at 8 weeks of age in male mice exposed to bisphenol A at both the 2 ng/g and 20 ng/g concentrations compared with a control group, but no difference was found after 12 weeks. Relative testis weight (per gram of body weight) was significantly lower at 8 and 12 weeks in mice treated with 2 ng/g than in controls (p < 0.05) and was significantly lower at 12 weeks in mice treated with 20 ng/g than in controls (p < 0.01). The serum testosterone concentration in treated mice was not significantly different from that in controls. These results demonstrate that bisphenol A temporarily activated aggressive behavior in mice at 8 weeks of age and that low doses of bisphenol A interfered with the normal development of reproductive organs. The mechanism activating this aggressive behavior was not elevated testosterone concentration.

An integrated inpatient therapy for type 1 diabetic females with bulimia nervosa: a 3-year follow-up study.

OBJECTIVE: To describe an "integrated inpatient therapy" for type 1 diabetic patients with recurrent binge eating and to assess its effectiveness for females with bulimia nervosa (BN). METHODS: At the first visit to our outpatient clinic for treatment of an eating disorder and diabetes, type 1 diabetic females with BN underwent single session "outpatient counseling." All patients then returned to the referring physician for further treatment and observation. None of the BN patients had the minimum expected 1% fall in HbA1c and all were therefore encouraged to undergo our "integrated inpatient therapy." However, only patients accepting inpatient treatment on their own volition were admitted. An "INPATIENT" group (n=9) consisted of those who underwent inpatient therapy and had a 3-year follow-up period after discharge. The clinical course was assessed by the HbA1c and BMI course and by comparison of psychological/behavioral factors between baseline and follow-up. For reference, the clinical course of a "NON-INPATIENT" group (n=10), who did not have the inpatient therapy for at least 2 years after first visit, was also assessed. RESULTS: The "INPATIENTs" had significantly lower HbA1c; lower psychological test scores related to eating disorder psychopathology, depressiveness, and anxiety-proneness; a reduced frequency and amount of binge eating; and fewer patients exhibited purging behaviors at follow-up than at first visit. At follow-up, seven (78%) "INPATIENTs" no longer fulfilled any criterion for clinical or subclinical eating disorders. The "NON-INPATIENTs" had no significant improvement. CONCLUSION: The findings give interesting insights into the possibilities of "integrated inpatient therapy" as an effective treatment for type 1 diabetic females with BN.

The outcome of treatment for anorexia nervosa inpatients who required urgent hospitalization.

BACKGROUND: This study was done to determine which psychosocial factors are related to the urgent hospitalization of anorexia nervosa patients (AN) due to extremely poor physical condition and to evaluate their outcome after inpatient treatment. METHODS: 133 hospitalized AN patients were classified into an urgent hospitalization (n = 24) or a planned hospitalization (n = 109) group. Multiple regression analysis was done of clinical features, body mass index (BMI), psychological tests [The Minnesota Multiphasic Personality Inventory (MMPI), alexithymia, relationship with parents, and the Eating Disorder Inventory (EDI)]. The effectiveness of treatment was prospectively determined two years after discharge by the Global Clinical Score (GCS). The hospitalized weight gain and the frequency of outpatient visits were evaluated. RESULTS: Of the factors assessed, only BMI at admission was related to the necessity of urgent hospitalization (ß = - 1.063, P = 0.00). The urgent group had significantly more weight loss after discharge and poorer social adaptation on the GCS, even when the patient had a sufficient increase in body weight during inpatient treatment and an equivalent number of outpatient consultations. CONCLUSION: None of the parameters of the psychosocial tests studied were significantly different between the groups. The outcome of the urgent group was poor. Two years after discharge they had difficulty maintaining weight and continued to have poor social adaptation.

The longitudinal BMI pattern and body composition of patients with anorexia nervosa who require urgent hospitalization: A case control study.

BACKGROUND: The prevention of serious physical complications in anorexia nervosa (AN) patients is important. The purpose of this study is to clarify which physical and social factors are related to the necessity for urgent hospitalization of anorexia nervosa (AN) patients in a long-term starvation state. We hypothesized that the change of longitudinal BMI, body composition and social background would be useful as an index of the necessity for urgent hospitalization. METHODS: AN patients were classified into; urgent hospitalization, due to disturbance of consciousness or difficulty walking(n = 17); planned admission (n = 96); and outpatient treatment only groups (n = 136). The longitudinal BMI pattern and the clinical features of these groups were examined. In the hospitalization groups, comparison was done of body composition variation and the social background, including the educational level and advice from family members. RESULTS: After adjusting for age and duration of illness, the BMI of the urgent hospitalization group was lower than that of the other groups at one year before hospitalization (P < 0.01) and decreased more rapidly (P < 0.01). Urgent hospitalization was associated with the fat free mass (FFM) (P < 0.01). Between the groups, no considerable difference in social factors was found. CONCLUSIONS: The longitudinal pattern of BMI and FFM may be useful for understanding the severity in AN from the viewpoint of failure of the homeostasis system.

A ghrelin gene variant may predict crossover rate from restricting-type anorexia nervosa to other phenotypes of eating disorders: a retrospective survival analysis.

BACKGROUND: Patients with anorexia nervosa restricting type (AN-R) often develop bulimic symptoms and crossover to AN-binge eating/purging type (AN-BP), or to bulimia nervosa (BN). We have reported earlier that genetic variants of an orexigenic peptide ghrelin are associated with BN. Here, the relationship between a ghrelin gene variant and the rate of change from AN-R to other phenotypes of eating disorders (EDs) was investigated. METHODS: Participants were 165 patients with ED, initially diagnosed as AN-R. The dates of their AN-R onset and changes in diagnosis to other subtypes of ED were investigated retrospectively. Ghrelin gene 3056 T-->C SNP (single nucleotide polymorphism) was genotyped. Probability and hazard ratios were analyzed using life table analysis and Cox's proportional hazard regression model, in which the starting point was the time of AN-R onset and the outcome events were the time of (i) onset of binge eating, that is, when patients changed to binge eating AN and BN and (ii) recovery of normal weight, that is, when patients changed to BN or remission. RESULTS: Patients with the TT genotype at 3056 T-->C had a higher probability and hazard ratio for recovery of normal weight. The ghrelin SNP was not related with the onset of binge eating. CONCLUSION: The 3056 T-->C SNP of the ghrelin gene is related to the probability and the rate of recovery of normal body weight from restricting-type AN.

Relation between psychosocial variables and the glycemic control of patients with type 2 diabetes: a cross-sectional and prospective study.

BACKGROUND: This cross-sectional and prospective study used a variety of psychological inventories to evaluate the relationship between psychosocial factors and the glycemic control of patients with type 2 diabetes. METHODS: Participants were 304 patients with type 2 diabetes who were treated as outpatients at diabetes clinics. All participants were assessed for HbA1c and completed the following self-report psychological inventories: 1) Diabetes Treatment Satisfaction Questionnaire (DTSQ), 2) Problem Areas in Diabetes Survey (PAID), 3) Well-being Questionnaire 12 (W-BQ12), 4) Self-Esteem Scale (SES), 5) Social Support Scale, and 6) Self-Efficacy Scale. HbA1c was again measured one year later. The relationships between the psychosocial variables obtained by analysis of the psychological inventories and baseline or one-year follow-up HbA1c were determined. RESULTS: Baseline HbA1cwas significantly correlated with age, diet treatment regimen, number of microvascular complication of diabetes, and the total scores of DTSQ, W-BQ12, PAID, SES and the Self-Efficacy Scale. Hierarchical stepwise multiple regression revealed that significant predictors of baseline HbA1c were total DTSQ and PAID scores, along with age, diet treatment regimen, and number of microvascular complication of diabetes after adjustment for demographic, clinical and other psychosocial variables. Two hundred and ninety patients (95.4% of 304) were followed and assessed one year after baseline. Hierarchical stepwise multiple regression analysis showed the significant predictors of follow-up HbA1c to be total DTSQ and PAID scores, along with age and diet treatment regimen. However, the correlation between baseline and follow-up HbA1c was so high that the only other variable to retain significance was diet treatment regimen once baseline HbA1c was included in the regression of follow-up HbA1c. CONCLUSION: The DTSQ and the PAID predicted both current and future HbA1c to a similar and significant degree in patients with type 2 diabetes.

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.

Psychopathological features of anorectic patients who dropped out of inpatient treatment as assessed by the Minnesota multiphasic personality inventory.

BACKGROUND: Anorexia nervosa often requires inpatient treatment that includes psychotherapeutic intervention in addition to physical and nutritional management for severe low body weight. However, such patients sometimes terminate inpatient treatment prematurely because of resistance to treatment, poor motivation for treatment, unstable emotions, and problematic behaviors. In this study, the psychopathological factors related to the personality of anorexic patients that might predict discontinuation of inpatient treatment were investigated using the Minnesota Multiphasic Personality Inventory (MMPI). METHODS: Subjects were 75 consecutive anorectic inpatients who received cognitive behavioral therapy with a behavior protocol governing privileges in a university hospital based general (not psychiatric) ward. The MMPI was done on admission for all patients. A comparison was done of patients who completed the process of inpatient treatment, including attainment of target body weight (completers), and patients who dropped out of inpatient treatment (dropouts). RESULTS: No significant differences between completers (n = 51) and dropouts (n = 24) were found in the type of eating disorder, age of onset, duration of illness, age, or BMI at admission. Logistic regression analysis found the MMPI scales schizophrenia (Sc), hypomania (HYP), deviant thinking and experience, and antisocial attitude to be factors predicting completion or dropout. CONCLUSION: Dropouts have difficulty adapting to inpatient treatment protocols such as our behavior protocol governing privileges because they have social and emotional alienation, a lack of ego mastery (Sc), emotional instability (HYP) and an antisocial attitude. As a result, they have decreased motivation for treatment, leave the hospital without permission, attempt suicide, or shoplift, which leads them to terminate inpatient treatment prematurely. Treatments based on cognitive behavioral therapy with a behavior protocol governing privileges should be carefully adopted for anorectic patients who exhibit the psychopathological elements identified in this study.

Changes in estrogen receptors alpha and beta expression in the brain of mice exposed prenatally to bisphenol A.

The expression of ERs alpha and beta and serotonergic neurons were evaluated in the brains of mice prenatally exposed to Bisphenol A, a known endocrine disrupting chemical (EDc). Bisphenol A was administered orally at a dose of 2ng/g body weight on gestinational days 11-17 to pregnant ICR mice. Newborn male offspring (Bis-A mice) were evaluated for the immunoreactivity of ERs alpha and beta, serotonin, and serotonin transporter positive cells in the dorsal raphe nucleus (DRN). The serum testosterone level was also evaluated. In the Bis-A mice, the expression of ERs alpha and beta at 5 and 13 weeks was increased compared with the controls (P<0.04), but this difference disappeared by the 9th week. The serotonin, serotonin transporter, and testosterone level differences between two groups did not reach significance. Exposure to bisphenol A may have changed the expression of ERs in the brain, but did not directly affect serotonin neurons in the DRN.

Possible role of preproghrelin gene polymorphisms in susceptibility to bulimia nervosa.

Previous investigations have suggested that ghrelin, an endogenous orexigenic peptide, is involved in the pathology of eating disorders. We conducted a study to determine whether any preproghrelin gene polymorphisms are associated with eating disorders. Three hundred thirty-six eating disorder patients, including 131 anorexia nervosa (AN)-restricting types (AN-R), 97 AN-binge eating/purging types (AN-BP) and 108 bulimia nervosa (BN)-purging types (BN-P), and 300 healthy control subjects participated in the study. Genotyping was performed to determine the polymorphisms present, and with this information, linkage disequilibrium (LD) between the markers was analyzed and the distributions of the genotypes, the allele frequencies, and the haplotype frequencies were compared between the groups. The Leu72Met (408 C > A) (rs696217) polymorphism in exon 2 and the 3056 T > C (rs2075356) polymorphism in intron 2 were in LD (D' = 0.902, r2 = 0.454). Both polymorphisms were significantly associated with BN-P (allele-wise: P = 0.0410, odds ratio (OR) = 1.48; P = 0.0035, OR = 1.63, for Leu72Met and 3056 T > C, respectively). In addition, we observed a significant increase in the frequency of the haplotype Met72-3056C in BN-P patients (P = 0.0059, OR = 1.71). Our findings suggest that the Leu72Met (408 C > A) and the 3056 T > C polymorphisms of the preproghrelin gene are associated with susceptibility to BN-P.