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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. © 2011 Wiley Periodicals, Inc.

In humans, ghrelin has been found to stimulate appetite while PYY3-36 to reduce it; these orexigenic and anorexigenic peptides play significant roles in appetite control. We investigated pre- and postprandial responses of ghrelin and PYY in anorexia nervosa (AN) and the influence of weight gain.Plasma ghrelin, PYY3-36, glucose and insulin responses after ingestion of a 400 kcal standard meal were measured in 14 patients with restricting type of AN and 12 controls. The AN patients were evaluated before therapy and after inpatient therapy. Psychometry was performed by the use of Eating Disorders Inventory.Ghrelin was suppressed during the meal test, while PYY3-36 was increased in all of the groups. Before therapy, AN patients had significantly increased levels of ghrelin and PYY3-36 compared to the control (P0.01). After therapeutic intervention, as the nutritional status of AN patients improved, the secretion of these hormones were increased (P0.05), but not normalized as in psychological testing. In contrast, insulin and glucose responses were normalized after inpatient therapy.We found that both ghrelin and PYY3-36 increased in AN patients and these changes were not normalized in contrast to insulin after treatment. The increase in both orexigenic ghrelin and anorexigenic PYY3-36 may have a role in pathological eating behavior in AN.

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.

We investigated changes in regional cerebral blood flow (rCBF) before and after weight gain in patients with restrictive anorexia nervosa (AN-R) in comparison with findings in normal subjects. We assessed resting rCBF using single photon emission computed tomography with technetium-99m hexamethylpropylene amine oxime in 12 AN-R patients and 11 controls. Each patient was examined at two time points, at the beginning of treatment and after weight gain (average examination interval=88+/-26 days). Control subjects were examined only once. Before treatment, the AN-R group had lower rCBF in the bilateral anterior lobes, including the anterior cingulate cortex (ACC), and in the right parietal lobe, the insula, and the occipital lobes. After weight gain, the patients showed significant increases in the right parietal lobe and decreases in the basal ganglia and cerebellum in accordance with significant improvement in body weight and eating attitudes. However, they showed persistent decreases in the ACC area even after weight gain compared with findings in the controls. A significant positive correlation was observed between body mass index and rCBF in the occipital lobes in the patients. These results suggest that weight gain is associated with a normalization of rCBF in a number of brain areas, but that the low level of rCBF in the ACC at baseline is unaffected by treatment in AN-R.

Summary Objective In recent years great advances have been made in our understanding of the peripheral signals produced within the gastrointestinal tract that regulate appetite, such as ghrelin and peptide YY (PYY). While ghrelin elicites hunger signals, PYY elicites satiety. Therefore, alterations in hormone physiology may play a role in the pathogenesis of bulimia nervosa (BN). In this study, we investigated the postprandial profile of ghrelin and PYY levels in patients with BN. Design and patients Postprandial plasma ghrelin and PYY levels and insulin and glucose responses were measured in 10 patients with BN and 12 control patients in response to a standard 400 kcal meal. Results Basal ghrelin levels present in BN subjects (265·0 ± 25·5 pmol/l) were significantly higher than those in healthy controls (199·3 ± 18·4 pmol/l, P

Background & aims : The aim of this study was to determine the relationship between insulinogenic index at 15 min (II 15 min ), body weight maintenance, and the presence of vomiting in patients with bulimia nervosa. Methods : Forty-eight bulimic inpatients and 14 controls underwent an oral glucose tolerance test on the seventh hospital day. We calculated II 15 min and other biological markers, including serum amylase concentrations. During the first week after admission, we monitored the frequency of vomiting and calculated changes in body weight. Patients were divided into 4 subgroups according to the presence of vomiting and weight loss. Results : Two-factor analysis of variance of the II 15 min value revealed significant main effects of vomiting and body weight change ( P 15 min values for controls and bulimic patients with weight loss and no vomiting were lower than those of other bulimic groups. The II 15 min values were positively correlated with serum amylase concentrations ( r =0.37, P r =0.35, P r =0.49, P Conclusions : These findings suggest that II 15 min values may be a useful marker for assessing the stability of eating behavior in patients with bulimia nervosa.

Summary OBJECTIVE Ghrelin is thought to be involved in the regulation of eating behaviour and energy metabolism in acute and chronic feeding states. Circulating plasma ghrelin levels in healthy humans have been found to decrease significantly after oral glucose administration. Because it is suggested that eating behaviour may influence the secretion of ghrelin and insulin in anorexia nervosa (AN), we examined the effect of oral glucose on ghrelin and insulin secretion in subtypes of AN patients. DESIGN AND PATIENTS Twenty female AN patients and 10 age-matched female controls were subjects. The patients were subdivided into two subtypes based on eating behaviour as follows: 11 restricting type (AN-R), nine binge-eating and purging type (AN-BP). Subjects underwent an oral glucose tolerance test at 08·00 h. Blood was collected 0, 30, 60, 120 and 180 min after the glucose load. RESULTS Both AN-R and AN-BP had a significant increased basal ghrelin level ( P < 0·01) and a significantly decreased basal insulin level ( P < 0·05) as compared to controls. The time of the nadir of mean ghrelin in ANBP (120 min, 58·1% of basal level, 204·9 ± ± ± 34·3 pmol/l, mean ± SEM) was delayed compared to controls (60 min, 60·2%, 74·3 ± 7·9 pmol/l), and in the AN-R group it kept decreasing for 180 min (80·0%, 182·4 ± 31·5 pmol/l). The peaks insulin levels in AN-BP (120 min, 319·3 ± ± ± 88·8 pmol/l) and AN-R (180 min, 418·9 ± 68·4 pmol/l) were also delayed as compared to controls (60 min, 509·2 ± 88·8 pmol/l). The glucose level at 180 min in AN-R was significantly ( P < 0·05) higher than in controls. CONCLUSIONS These findings suggest that differences in eating behaviour in AN may induce alterations in both ghrelin and insulin metabolism in the acute feeding state. Furthermore, metabolic changes in the restrictive eating pattern may be related to the pathophysiology of small quantitative meal intake in AN-R patients.

Ghrelin has a role in regulating eating behavior and energy metabolism in the central nervous system, and has been reported to play an important role in the pathophysiology of anorexia nervosa (AN). The aim of the present study was to compare fasting plasma ghrelin levels in different subtypes of untreated AN patients. The subjects included 39 female AN patients and 11 female controls. The patients were then divided into two subtypes as follows: 19 AN patients with restricting (AN-R) and 20 AN patients with binge-eating/purging (AN-BP) form of the illness. Blood samples from subjects after an overnight fast were used to analyze plasma ghrelin concentrations. Plasma ghrelin concentrations in both AN-R and AN-BP were negatively correlated with body mass index (BMI). The mean plasma ghrelin levels in both AN-R and AN-BP were significantly higher than that in controls. The mean ghrelin level in AN-BP was significantly higher than that in AN-R. However, mean BMI and serum potassium in both groups were not significantly different. These results suggest that both BMI and the presence of binge-eating/purging may have some influence on fasting plasma ghrelin levels in patients with AN.

Background: Insulin responses to the oral-glucose-tolerance test (OGTT) in anorexia nervosa (AN) are related to body weight and show various patterns. Although weight gain is a key indicator of a successful nutritional program, it is not a sufficiently accurate index for assessing nutritional status, especially in the periods of marked fear of obesity, because patients often manipulate body weight measurements. Objective: The aim of this study was to determine the relation between insulin metabolism during the early phase of the OGTT and progress (weekly weight gain) during nutritional rehabilitation. Design: Forty-eight inpatients with AN (25 AN restricting type and 23 AN bulimic type) underwent the OGTT, with additional blood sampling at 15 min, when energy intake reached 6694 kJ/d (1600 kcal/d). Thirteen healthy volunteers were also studied. To evaluate early-phase insulin metabolism, we calculated the insulinogenic index after 15 (II 15 min ) and 30 min. On the basis of weekly changes in body weight, the AN participants were divided into good (≥ 0.5 kg) and poor (< 0.5 kg) responders. Results: Among the AN patients, 48% were poor responders. Analysis of variance showed significant differences in the II 15 min values (P = 0.0005) and showed that II 15 min values for good responders were significantly higher than those for the other groups. Conclusions: These findings suggest that a lack of progress in weight gain is frequently observed in AN and that II 15 min values may be a useful marker with which to assess the weekly progress during nutritional rehabilitation. Am J Clin Nutr 2003;77:292‐9.

Previous studies have reported that fasting plasma ghrelin concentrations play an important role in the pathophysiology of eating disorders. The purpose of this study was to examine the relationship between plasma ghrelin levels and frequency of abnormal eating behaviors, nutritional parameters in eating disorders. Fasting blood samples were obtained in 40 female anorexia nervosa (AN) patients, 21 restricting type (AN-R) and 19 binge-eating/purging type (AN-BP), in 31 bulimia nervosa (BN) patients, 18 purging type (BN-P) and 13 nonpurging type (BN-NP), in 15 female healthy volunteers (control) before the initiation of active treatment. The fasting plasma ghrelin concentrations in all subjects were negatively correlated with nutritional parameters such as body mass index, percent body fat and serum cholinesterase concentration. The mean plasma ghrelin level in BN-P was higher than that in both BN-NP and controls despite similar nutritional parameters. The plasma ghrelin levels in both AN-R and AN-BP did not differ from BN-P despite difference of nutritional parameters. For both AN-BP and BN-P patients with habitual binge/purge behavior, there were significant correlations among plasma ghrelin values, frequencies of binge/purge cycles and serum amylase values. In BN-NP, there were no significant correlations among plasma ghrelin values, frequencies of binge-eating episodes and serum amylase values. These results suggest that habitual binge/purge behavior may have some influence on circulating plasma ghrelin levels in both BN-P and AN-BP. Habitual binge/purge cycles with vomiting as opposed to binge-eating episodes without vomiting may have a greater influence on fasting plasma ghrelin concentration in eating disorders.

Objective: To investigate the prevalence and the clinico-epidemiological features of eating disorders (ED) in Japan. Methods: In January 1998, a self-reported questionnaire, asking about the number of ED was mailed to 23,401 institutions and a second questionnaire asking about the clinoco-epidemiological features of ED was mailed to 1404 institutions, the institutions being located throughout Japan. We calculated the 1-year prevalence rates of ED from these data. Results: The prevalence rates of anorexia nervosa in this survey showed 10.0 cases per 100,000 of general population, which were four times higher than those in 1993. The rates for bulimia nervosa indicated 5.2 cases per 100,000, which were 4.7 times higher than in 1993. With respect to clinico-epidemiological features, short-term cases (duration of illness 9 years). Moreover, fewer than half of ED patients indicated “improved” in clinical course, “sufficient” in family support and “adjusted” in social adaptation. Conclusions: These findings suggest the expansion of age groups with ED, vulnerable family structure, and insufficient social support systems in contemporary Japan, and also suggested that the prevalence rates in Japan would soon reach those in the west.

Multidisciplinary team approach to eating disorders (ED) mainly utilizing behavior therapy including cognitive, group and family therapy has been implemented in our hospital. In order to assess usefulness of our treatment, we investigated the long-term (more than 4 years after discharge) prognosis of the 68 inpatients with ED consisting of restrictive anorexia nervosa (AN) (AN-R), AN with binge-eating/purge (AN-BP) and bulimia nervosa (BN) by using newly developed checklist for ED in Japan. We defined the score and five outcome criteria. We found that 51.5% (n=35) of the patients was excellent, 17.9% (n=12) was much improved, 11.9% (n=8) was symptomatic and 11.9% (n=8) poor and 7.4% (n=5) had died. AN-R had the youngest average age at admission, shortest duration of illness and smallest body mass index at admission. Around 84% of AN-R patients had reached the level of excellent or much improved outcome, though only around 61% of AN-BP patients and 50% of BN patients showed excellent or much improved outcome. In conclusion, the present findings indicate that our treatment is effective for ED patients, especially AN-R. However, in order to improve the effectiveness of treatment for AN-BP and BN, we should further develop every system of the treatment strategy.

In addition to traditional morphological and functional strategies, including physiological and pharmacological tools, innovative approaches are necessary to investigate molecular, cellular and neuroendocrine correlates of behavior. Neuroendocrine as well as behavioral regulation, particularly in mammals, is a priori complex at multiple levels, justifying the use of various complementary techniques. Among them, antisense targeting has proven to be a valuable tool for studying peptide and protein functions in vivo even in the intact brain, which provides a particular challenge but also a promise for those interested in antisense targeting. On the one hand, both the blood–brain barrier and the heterogeneity of the brain make efficient and selective antisense targeting difficult to achieve. But on the other hand, the brain as a whole or even an individual neuron with its capability of producing hundreds of biologically active neuropeptides and receptor and other proteins may be particularly amenable to the use of antisense approaches, especially when few specific traditional pharmacological agents exist. In neuroendocrinology those antisense studies dominate that focus on neuropeptides and receptors of neuropeptides or steroids. The number of such studies using antisense targeting in vivo peaked in 1994 and 1995, with about 20 papers published in each of those years (in 1993, about 5 papers were published and in 1996, about 15). This development, which is similar for corresponding behavioral studies (including those on autonomic effects; from 1993 to 1996 about 10, 30, 25 and 20 papers respectively were published), appears to be normal for a new and promising technique and reflects the initial enthusiasm just as much as its subsequent more expert use and the realization of considerable pitfalls. The antisense papers published so far in behavioral neuroscience (including autonomic effects) have described effects on (order according to the number of published papers) antinociception, motor regulation, feeding and drinking, reproductive behaviors, anxiety, learning and memory, and on cardiovascular and temperature regulation. By weighing the advantages and disadvantages of antisense targeting, this short review is aimed at stimulating and qualifying the reader to use antisense oligodeoxynucleotides (ODN) in vivo to study mechanisms underlying the regulation of neuroendocrine systems and behavior. Although a detailed methodological discussion is beyond the scope of this article and the methodology has already been reviewed by others (1–8), some of the problems we are facing in the actual application of antisense ODN to the brain of conscious rats are briefly discussed in terms of administration, chemical modification, proper controls, mechanisms of antisense action and specificity in vivo. Furthermore, this review will highlight the literature on antisense effects on neuroendocrine systems and behavioral performance, with emphasis on those studies that include both neuroendocrine and behavioral parameters as well as our own attempts in this direction.

OBJECTIVE: Fasting plasma ghrelin levels play an important role in the pathophysiology of the eating disorder anorexia nervosa. Bulimia nervosa (BN) also has been associated with abnormal neuroendocrine regulation. Thus, we examined the relationship between body mass index (BMI) and plasma ghrelin concentrations in patients with BN for the first time. METHODS: The subjects included 15 female BN patients and 11 female healthy volunteers (controls). Fasting blood samples were collected from all subjects. RESULTS: The plasma ghrelin concentrations in all subjects demonstrated a significantly negative correlation with BMI. Mean plasma ghrelin level in BN patients was significantly higher than that in the controls, though mean BMIs between the groups were not significantly different. CONCLUSION: These findings suggest that not only BMI but also abnormal eating behaviors with habitual binge eating and purging may have some influence on circulating ghrelin level in BN.

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.

Effects of dosing time of trazodone hydrochloride, (KB-831), a new antidepressant drug, on the pharmacokinetics were investigated by a cross-over method using 6 healthy male volunteers administered 50mg of the drug orally after breakfast or after supper. There were some effects of dosing time on the pharmacokinetics of trazodone hydrochloride, showing significantly higher Cmax and significantly larger AUC0-24hr in the group administered in the morning than in the evening. Mild drowsiness, dizziness, and dry mouth observed after the administration of trazodone hydrochloride were relatively stronger in the group administered in the morning than in the evening. From these results, it could be presumed that a single oral administration of the drug before sleep might be better for the reduction of the side effects of the drug.

The dose-response relation (study I) and the effect of the timing of administration (study II) with respect to the antihistaminic activity of a H1-blocking agent, WAL 801 CL (Epinastine), were investigated. In study I, a 10, 20, and 40mg dose of WAL 801 CL or a placebo was administered to 11 healthy male volunteer students (X±SD=23.3±1.3yrs) after breakfast (8:30) by a double-blind fashion using the Latin square design, and the histamine intradermal reaction and psychomotor functions were subsequently examined. In study II, either 20mg of WAL 801 CL or a placebo were administeredto 8 healthy male volunteer students (23.8±1.4yrs) after breakfast (8:00) or after dinner (20:30) in the same way as in Study I, and the histamine intradermal reaction was subsequently examined. WAL 801 CL inhibited the histamine intradermal reaction dose-dependently, and no findings suggesting any effects on the CNS were observed. The inhibitory effect of WAL 801 CL on the histamine intradermal reaction tended to last longer when it was administered in the morning, while the effect tended to be stronger when it was administered in the evening, but the differences were not significant. Thus the results show that WAL 801 CL is a nonsedative H1-blocking agent and that the timing of administration does not critically influence the antihistaminic activity of the drug.

Non-steroidal antiinflammatory drug (NSAID) challenge tests were given to patient with aspirin-induced asthma (AIA) to observe the changes of the forced expiratory volume in one second (FEV1.0) between before and after challenges.PL granules for children (PL®) as acid NSAID, that consists of 45 mg salicylamide, 25mg acetaminophen and 10 mg anhydrous caffein per gram, mepirizole and tiaramide hydrochloride as basic NSAID, and syoseiryuto as chinese traditional medicine were used.FENT1.0 was measured before and several times after oral challenges of NSAIDs and syoseiryuto, and decrease of more than 20% of the initial value (basal value) was defined as a positive response.PL, Acid NSAID, showed clear positive response 30 min after challenge, but basic NSAID mepirizole and chinese traditional medicine syoseiryuto showed negative response.On the other hand, tiaramide hydrochloride, that is also basic NSAID, showed positive response when administered 40 mg although negative in a dose of 20 mg.These results suggest that the administration of NSAID to patient with AIA, even in a case of basic NSAID, must be done carefully, and it should be carried out as challenge tests in those cases.

PP administration induces negative energy balance by suppressing food intake and gastric emptying while increasing energy expenditure in rodents. The mechanism of PP actions involves the changes in the expression of hypothalamic feeding-regulatory peptides and the activity of the vago-vagal and vago-sympathetic reflex arc. PP-overexpressing mice we developed exhibited the thin phenotype with decreased food intake and gastric emptying rate. Plasma cholecystokinin (CCK) concentrations were increased in the transgenic mice and CCK-1 receptor antagonist improved the anorexia of the animals. These results, together with the previous notion of PP as an anti-CCK hormone in pancreatic exocrine secretion and gallbladder contraction, indicate that PP-CCK interactions may be either antagonistic or synergistic and the transgenic mice may exhibit the mixed phenotype by overproduction of PP and CCK.

Objective The extent of renal damage over long-term binge/purges has not been well documented in bulimia nervosa (BN). Method We describe a 52-year-old woman with longstanding BN subsequent to an 8-year history of anorexia nervosa (AN). Results The patient showed chaotic binge/purges and chronic severe hypokalemia after recovery from AN at age 26 years, and renal biopsy showed juxtaglomerular hyperplasia, which was diagnosed as pseudo-Bartter's syndrome. Discussion Over the following 26 years, the patient's eating behaviors remained chaotic, and her renal function gradually deteriorated. After the patient died of pneumonia and sepsis at age 52 years, autopsy of her kidney showed chronic interstitial nephritis, proximal tubular swelling, and diffuse glomerular sclerosis, suggesting chronic glomerular injury associated with long-term binge/purges. To our knowledge, this is the first case report of a patient with BN with long-term binge/purges who developed an eventual “end-stage kidney” characterized by hypokalemic nephropathy and diffuse glomerulosclerosis. © 2005 by Wiley Periodicals, Inc. Int J Eat Disord 38: xxx–xxx, 2005.

Objective Osteoporosis is recognized as a common medical complication of anorexia nervosa (AN). The purpose of the current study was to investigate the recovery mechanism of osteoporosis in AN and the effect of medical treatment on the skeletal system. Method We conducted a randomized placebo-controlled study of the effects of etidronate and calcium and vitamin D on bone loss in 41 outpatients with the restricting type of AN (AN-R). We measured the tibial speed of sound (SOS) before and after 3 months of treatment. Results The bone mineral density (BMD) of the tibial SOS change in both the etidronate group and the calcium and vitamin D Group was significantly greater (p < .001) than in the control group. Urine-N-telopeptide cross-links of type I collagen (NTx) before and after treatment decreased significantly (p < .01) in the etidronate group. Conclusion These findings suggest that both etidronate and calcium and vitamin D are equally efficacious for reversing the degree of osteoporosis in patients with AN. © 2005 by Wiley Periodicals, Inc.

Objective: Little is known about biologic predictors of refeeding outcome in anorexia nervosa (AN). Because nutritional status mirrors glucose metabolism during an oral glucose tolerance test (OGTT) in AN, this study investigated whether pretreatment glucose response patterns during the OGTT might be associated with refeeding progress in patients with AN. Methods: Sixty-four female patients with anorexia (33 restrictors and 31 binge/purgers) and 13 healthy control subjects underwent an OGTT before nutritional rehabilitation, including desensitization to fear of energy intake of 1000 to 1600 kcal/day. Patients were divided into flat-type responders, impaired glucose tolerance (IGT)-type responders, and normal-type glucose responders. Daily energy intake, weekly weight gain, and the duration of desensitization period were evaluated until the 12th week. Results: The patients with anorexia consisted of 20 flat-type, 21 IGT-type, and 23 normal- type responders. Normal-type responders required a shorter time to complete the desensitization period than other responders (p .003 for restrictors, p .001 for binge/purgers). In terms of refeeding progress, significant group effects for daily energy intake and weekly weight gain were evident in restrictors (p .006, p .028, respectively) and binge/purgers (p .001, p .003, respectively); normal-type responders showed good refeeding progress compared with other responders in both AN subtypes. Conclusions: The present study found a close relationship between pretreatment glucose responses, therapeutic progress of desensitization to fear of energy intake, and refeeding progress in both AN subtypes. Our findings suggest that glucose tolerance may be a useful predictor of short-term refeeding outcome in this disorder. AN anorexia nervosa; ANOVA analysis of variance; AUC insulin area under the curve; BMI body mass index; DM diabetes mellitus; DSM-IV Diagnostic and Statistical Manual of Mental Disorders, fourth edition; FBG fasting blood glucose concentration; FIRI fasting serum insulin concentration; HOMAIR homeostasis model assessment for insulin resistance; IGT impaired glucose tolerance; II15min insulinogenic index at 15 minutes; OGTT oral glucose tolerance test.

Refeeding outcome is difficult to predict in anorexia nervosa (AN). Because reactive hypoglycemia (RH) during an oral glucose tolerance test (OGTT) correlates with rapid increases of energy intake just before the OGTT in AN patients, this study investigated whether pretreatment laboratory-measured RH episodes might be associated with refeeding progress in this disorder. Forty-six female patients with AN (25 restrictors and 21 binge/purgers) and 11 controls underwent an OGTT before treatment. The patients were divided into groups according to the presence of RH. Thereafter, AN patients underwent nutritional rehabilitation, and weight gain and daily energy intake were evaluated. In both AN subtypes, the RH groups showed more daily energy intake and gained more weight compared with the non-RH groups. The present study found a close relationship between pretreatment laboratory-measured RH episodes and refeeding progress, suggesting that pretreatment laboratory-measured RH episodes may be an important predictor of short-term refeeding outcome in AN.

Study Design. A trial of brace therapy modified by a measured personality pattern of patients with idiopathic scoliosis was performed. Objective. To evaluate the effectiveness of performing personality tests for patients with idiopathic scoliosis who undergo brace therapy. Summary of Background Data. Brace therapy has often been used for the treatment of scoliosis. However, emotional distress can result from this therapy. Few attempts have been made to reduce such stress. Methods. A test using the Maudsley Personality Inventory was performed on 145 adolescent females with idiopathic scoliosis, treated with brace therapy alone, before the start of brace therapy and 1 month after the start of brace therapy. On the basis of test results, the patients were rated as normal type and four abnormal types. Brace therapy was continued considering the personality pattern of patients. For all patients, changes in psychologic test results, compliance with braces wearing instructions, and correction of scoliosis were analyzed. Result. Of the 134 patients rated as normal before the start of therapy, 108 patients were rated as abnormal pattern when tested 1 month after the start of therapy. After performing autogenic training for patients with EN and EN personalities, and giving advice to school teachers to decrease the emotional stress for patients with EN personality, 47 patients were finally rated as abnormal pattern. In total, 12 (8%) of the 145 patients dropped out. In dropouts, the average pretreatment deformity of 29° (range: 21°‐37°) had increased to an average of 37° (range, 31°‐48°). Conclusion. Psychologic tests may be useful and provide a means of modifying brace therapy tailored to the psychologic conditions of individual patients.

Energy expenditure abnormalities have been observed in anorexia nervosa (AN). The uncoupling proteins (UCPs) have been implicated as having a role in energy metabolism and thermogenesis, and an association between a marker flanking the UCP-2/UCP-3 gene cluster and AN has been reported. Also known are insertion/deletion and -866G/A polymorphisms in the UCP-2 gene, and the -55C/T polymorphism in the UCP-3 gene. Differences in these alleles are reportedly related to changes in energy expenditure, body mass index, fat tissue accumulation and obesity. Therefore, this case-control association analysis was done to determine whether any of these UCP-2/3 gene polymorphisms are related to a predisposition to AN. In analysis of a cohort of 106 female Japanese AN sufferers and 126 normal female controls, we found no between-group differences in the polymorphism frequencies of these groups. The hypothesis that differences in the UCP-2/3 gene influence the susceptibility to AN was not supported.

Circulating ghrelin and growth hormone (GH) are up-regulated in anorexia nervosa (AN) as a consequence of prolonged starvation. The current study examines the effect of nutritional rehabilitation with improvement of eating behavior on ghrelin and GH levels in AN patients during the course of inpatient treatment. The subjects included 34 female AN patients and 9 age-matched female controls. Fasting blood samples were collected before, during and after treatment. For data analysis, AN subjects were divided into three subtypes. The first group included seven patients with emergent hospitalization (E-AN), who were accompanied by severe emaciation due to their inability for food intake for more than a month. The other two groups included 14 AN with restricting (AN-R) and 13 AN with binge-eating/purging (AN-BP) patients. There were significant correlations between ghrelin, GH and body mass index (BMI) before treatment in all subjects. However, ghrelin levels were not significantly correlated with BMI and GH although there was a relationship between GH and BMI after treatment. Before treatment, E-AN patients had the highest levels of ghrelin and GH with the lowest glucose levels and liver dysfunction. The AN-BP group had a higher level of ghrelin than the AN-R group. During treatment, comparing with the controls group only the AN-R group showed higher level of ghrelin. Contrarily, the ghrelin levels in the E-AN group, who showed improved glucose levels, and the AN-BP group, who stopped vomiting behavior due to our treatment, decreased ghrelin levels. After treatment, only the AN-BP group showed a higher ghrelin level as compared to the controls. Although GH levels of the three AN groups decreased gradually according to our treatment progress, it still showed the higher value than the control group at the end of the treatment because every AN patients could not reach to more than 80% of their ideal body weight at discharge. These findings suggest that (1) severe emaciation with abnormal fasting hypoglycemia in AN patients may cause very high levels of GH and ghrelin, (2) that GH levels in AN patients may relate to nutritional status and (3) that ghrelin may be influenced by not only nutritional status but also the eating behavior of the patients.

Ghrelin is thought to be involved in the regulation of eating behaviour and energy metabolism in acute and chronic feeding states. Circulating plasma ghrelin levels in healthy humans have been found to decrease significantly after oral glucose administration. Because it is suggested that eating behaviour may influence the secretion of ghrelin and insulin in anorexia nervosa (AN), we examined the effect of oral glucose on ghrelin and insulin secretion in subtypes of AN patients.Twenty female AN patients and 10 age-matched female controls were subjects. The patients were subdivided into two subtypes based on eating behaviour as follows: 11 restricting type (AN-R), nine binge-eating and purging type (AN-BP). Subjects underwent an oral glucose tolerance test at 08.00 h. Blood was collected 0, 30, 60, 120 and 180 min after the glucose load.Both AN-R and AN-BP had a significant increased basal ghrelin level (P0.01) and a significantly decreased basal insulin level (P0.05) as compared to controls. The time of the nadir of mean ghrelin in AN-BP (120 min, 58.1% of basal level, 204.9 +/- 34.3 pmol/l, mean +/- SEM) was delayed compared to controls (60 min, 60.2%, 74.3 +/- 7.9 pmol/l), and in the AN-R group it kept decreasing for 180 min (80.0%, 182.4 +/- 31.5 pmol/l). The peaks insulin levels in AN-BP (120 min, 319.3 +/- 88.8 pmol/l) and AN-R (180 min, 418.9 +/- 68.4 pmol/l) were also delayed as compared to controls (60 min, 509.2 +/- 88.8 pmol/l). The glucose level at 180 min in AN-R was significantly (P0.05) higher than in controls.These findings suggest that differences in eating behaviour in AN may induce alterations in both ghrelin and insulin metabolism in the acute feeding state. Furthermore, metabolic changes in the restrictive eating pattern may be related to the pathophysiology of small quantitative meal intake in AN-R patients.

The relationship among reactive hypoglycemia, corresponding insulin metabolism, and eating behavior in anorexia nervosa (AN) has not been well documented. Method A 22-year-old woman with AN was admitted to Kagoshima University Hospital. An oral glucose tolerance test was performed with additional sampling at 15 minutes on the seventh hospital day when her daily caloric intake rapidly increased, reaching 2,000kcal perday. Results An elevated level of insulin secretion (1,190pmol/L) was observed during the very early phase (15 minutes) after glucose load, whereas corresponding blood glucose elevations were not as high (1.2mmol/L). The patient experienced asymptomatic hypoglycemia (2.1mmol/L). Conclusions Our findings suggested that a rapid increase of energy intake might cause reactive hypoglycemia with characteristic insulin metabolism, that is, an elevated level of insulin secretion during the very early phase. © 2003 by Wiley Periodicals, Inc. Int J Eat Disord 34: 273–277, 2003.

Background It is possible that psychopathological differences exist between the restricting and bulimic forms of anorexia nervosa. We investigated localized differences of brain blood flow of anorexia nervosa patients using SPECT image analysis with statistic parametric mapping (SPM) in an attempt to link brain blood flow patterns to neurophysiologic characteristics. Methods The subjects enrolled in this study included the following three groups: pure restrictor anorexics (AN-R), anorexic bulimics (AN-BP), and healthy volunteers (HV). All images were transformed into the standard anatomical space of the stereotactic brain atlas, then smoothed. After statistical analysis of each brain image, the relationships among images were evaluated. Results SPM analysis of the SPECT images revealed that the blood flow of frontal area mainly containing bilateral anterior cingulate gyri (ACC) was significantly decreased in the AN-R group compared to the AN-BP and HV groups. Conclusions These findings suggest that some localized functions ofthe ACCare possibly relevant to the psychopathological aspects of AN-R.

The authors' goal was to investigate the effect of imagining food on the regional cerebral blood flow (rCBF) of anorexia nervosa patients with and without habitual binge/purge behavior.The subjects included seven female patients with purely restrictive anorexia, seven female patients with anorexia and habitual binge/purge behavior, and seven healthy women. Single photon emission computed tomography examination was performed before and after the subjects were asked to imagine food. Changes in rCBF count ratios (percent change) were then calculated and compared. The subjects were also asked to assess their degree of fear regarding their control of food intake.The anorexia nervosa patients with habitual binge/purge behavior had a significantly higher percent change in the inferior, superior, prefrontal, and parietal regions of the right brain than the patients with purely restrictive anorexia and the healthy volunteers. The patients with habitual binge/purge behavior also had the highest level of apprehension in regard to food intake.Specific activation in cortical regions suggests an association between habitual binge/purge behavior and the food recognition process linked to anxiety in patients with anorexia nervosa.

The purpose of this study is visual evaluation of the distribution of I-123 iomazenil in the brains of patients with various types of mental disorder and to examine whether chronic administration of a clinical dose of benzodiazepine (BZ) affects the binding of I-123 iomazenil to BZ receptors (BZR). The subjects were 10 patients with mental disorders (3 males and 7 females) with a mean age of 26.8 yrs (range 19-39 yrs). Four of 10 patients were administered BZ for over 3 months and the other six were free of BZ for over one month. The SPECT images were obtained at 5-25 min (early) and 170-190 min (delayed), after the bolus i.v. injection of 167 MBq of I-123 iomazenil, with a triple-head gamma camera. The images were visually evaluated and the washout ratios of each region were calculated. In visual analysis, abnormalities were recognized in 5 patients on the delaye SPECT. The abnormalities were recognized more frequently in the superior frontal lobe. The washout ratio was higher in the BZ (+) patient group than in the BZ (-) patient group. I-123 iomazenil is useful, because the SPECT image with I-123 iomazenil reflects the distribution of BZR on the brain and provides the different information from that obtained with perfusion SPECT, X-ray CT or MRI. The rapid washout of I-123 iomazenil from the brains of BZ (+) patients suggests that chronic administration of a clinical dose of BZ affects the binding of I-123 iomazenil to BZR.

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.