Changes of plasma obestatin, ghrelin and NPY in anorexia and bulimia nervosa patients before and after a high-carbohydrate breakfast

Peptides ghrelin, obestatin and neuropeptide Y (NPY) play an important role in regulation of energy homeostasis, the imbalance of which is associated with eating disorders anorexia (AN) and bulimia nervosa (BN). The changes in ghrelin, obestatin and NPY plasma levels were investigated in AN and BN patients after administration of a high-carbohydrate breakfast (1604 kJ). Eight AN women (aged 25.4+/-1.9, BMI: 15.8+/-0.5), thirteen BN women (aged 22.0+/-1.05, BMI: 20.1+/-0.41) and eleven healthy women (aged 25.1+/-1.16, BMI: 20.9+/-0.40) were recruited for the study. We demonstrated increased fasting ghrelin in AN, but not in BN patients, while fasting obestatin and NPY were increased in both AN and BN patients compared to the controls. Administration of high-carbohydrate breakfast induced a similar relative decrease in ghrelin and obestatin plasma levels in all groups, while NPY remained increased in postprandial period in both patient groups. Ghrelin/obestatin ratio was lower in AN and BN compared to the controls. In conclusions, increased plasma levels of fasting NPY and its unchanged levels after breakfast indicate that NPY is an important marker of eating disorders AN and BN. Different fasting ghrelin and obestatin levels in AN and BN could demonstrate their diverse functions in appetite and eating suppression.     

Neuroendocrine dysregulation of food intake in eating disorders

Anorexia nervosa (AN) and bulimia nervosa (BN) are psychiatric disorders characterized by abnormal eating behaviors and imbalance of energy homeostasis. Changes of both central and peripheral neuroendocrine substances involved in the modulation of food intake and energy expenditure have been described in acutely ill patients with eating disorders. This review selectively focuses on the most recent findings supporting abnormal changes in the physiology of some peripheral adipokines and gut-secreted peptides, brain-derived neurotrophic factor and endocannabinoids in patients with AN or BN. Literature data do suggest a dysregulation of these neuroendocrine feeding regulators but, at the moment, they do not allow to establish the state or trait-dependent nature of those aberrations. It has been proposed, although not definitively proved, that neuroendocrine alterations, even when secondary to malnutrition and/or to aberrant eating behaviors, might contribute to the genesis and the maintenance of some symptomatic aspects of AN and BN, thus affecting the course and the prognosis of these disorders. Future studies should clarify whether neuroendocrine alterations are part of the genetically transmitted biological vulnerability to eating disorders.     

Possible involvement of brain-derived neurotrophic factor in eating disorders

Eating disorders (EDs) manifest as abnormal patterns of eating behavior and weight regulation driven by low self-esteem due to weight preoccupation and perceptions toward body weight and shape. Two major groups of such disorders are anorexia nervosa (AN) and bulimia nervosa (BN). The etiology of EDs is complex and evidence indicates that both biological/genetic and psychosocial factors are involved. Several lines of evidence indicate that brain-derived neurotrophic factor (BDNF) plays a critical role in regulating eating behaviors and cognitive impairments in the EDs. BDNF is involved in neuronal proliferation, differentiation, and survival during development. BDNF and its tyrosine kinase receptor (TrkB) are expressed in hypothalamic nuclei associated with eating behaviors. A series of studies using BDNF knockout mice and the human BDNF gene indicate an association of BDNF and EDs with predisposition and vulnerability. In the previous studies, serum BDNF levels in subjects with EDs are reduced significantly compared with healthy controls, hence, we proposed that levels of serum BDNF would be a useful diagnostic indicator for EDs.     

Altered brain-derived neurotrophic factor blood levels and gene variability are associated with anorexia and bulimia

Murine models and association studies in eating disorder (ED) patients have shown a role for the brain-derived neurotrophic factor (BDNF) in eating behavior. Some studies have shown association of BDNF -270C/T single-nucleotide polymorphism (SNP) with bulimia nervosa (BN), while BDNF Val66Met variant has been shown to be associated with both BN and anorexia nervosa (AN). To further test the role of this neurotrophin in humans, we screened 36 SNPs in the BDNF gene and tested for their association with ED and plasma BDNF levels as a quantitative trait. We performed a family-based association study in 106 ED nuclear families and analyzed BDNF blood levels in 110 ED patients and in 50 sib pairs discordant for ED. The rs7124442T/rs11030102C/rs11030119G haplotype was found associated with high BDNF levels (mean BDNF TCG haplotype carriers = 43.6 ng/ml vs. mean others 23.0 ng/ml, P = 0.016) and BN (Z = 2.64; P recessive = 0.008), and the rs7934165A/270T haplotype was associated with AN (Z =-2.64; P additive = 0.008). The comparison of BDNF levels in 50 ED discordant sib pairs showed elevated plasma BDNF levels for the ED group (mean controls = 41.0 vs. mean ED = 52.7; P = 0.004). Our data strongly suggest that altered BDNF levels modulated by BDNF gene variability are associated with the susceptibility to ED, providing physiological evidence that BDNF plays a role in the development of AN and BN, and strongly arguing for its involvement in eating behavior and body weight regulation.     

Differential neural responses to food images in women with bulimia versus anorexia nervosa

Background

Previous fMRI studies show that women with eating disorders (ED) have differential neural activation to viewing food images. However, despite clinical differences in their responses to food, differential neural activation to thinking about eating food, between women with anorexia nervosa (AN) and bulimia nervosa (BN) is not known.

Methods

We compare 50 women (8 with BN, 18 with AN and 24 age-matched healthy controls [HC]) while they view food images during functional Magnetic Resonance Imaging (fMRI).

Results

In response to food (vs non-food) images, women with BN showed greater neural activation in the visual cortex, right dorsolateral prefrontal cortex, right insular cortex and precentral gyrus, women with AN showed greater activation in the right dorsolateral prefrontal cortex, cerebellum and right precuneus. HC women activated the cerebellum, right insular cortex, right medial temporal lobe and left caudate. Direct comparisons revealed that compared to HC, the BN group showed relative deactivation in the bilateral superior temporal gyrus/insula, and visual cortex, and compared to AN had relative deactivation in the parietal lobe and dorsal posterior cingulate cortex, but greater activation in the caudate, superior temporal gyrus, right insula and supplementary motor area.

Conclusions

Women with AN and BN activate top-down cognitive control in response to food images, yet women with BN have increased activation in reward and somatosensory regions, which might impinge on cognitive control over food consumption and binge eating.     

Characteristics of suicide attempts in anorexia and bulimia nervosa: a case-control study

Objective

Compared to other eating disorders, anorexia nervosa (AN) has the highest rates of completed suicide whereas suicide attempt rates are similar or lower than in bulimia nervosa (BN). Attempted suicide is a key predictor of suicide, thus this mismatch is intriguing. We sought to explore whether the clinical characteristics of suicidal acts differ between suicide attempters with AN, BN or without an eating disorders (ED).

Method

Case-control study in a cohort of suicide attempters (n = 1563). Forty-four patients with AN and 71 with BN were compared with 235 non-ED attempters matched for sex, age and education, using interview measures of suicidal intent and severity.

Results

AN patients were more likely to have made a serious attempt (OR = 3.4, 95% CI 1.4–7.9), with a higher expectation of dying (OR = 3.7,95% CI 1.1–13.5), and an increased risk of severity (OR = 3.4,95% CI 1.2–9.6). BN patients did not differ from the control group. Clinical markers of the severity of ED were associated with the seriousness of the attempt.

Conclusion

There are distinct features of suicide attempts in AN. This may explain the higher suicide rates in AN. Higher completed suicide rates in AN may be partially explained by AN patients'' higher desire to die and their more severe and lethal attempts.     

Poor cognitive flexibility in eating disorders: examining the evidence using the Wisconsin Card Sorting Task

Background

People with eating disorders (ED) frequently present with inflexible behaviours, including eating related issues which contribute to the maintenance of the illness. Small scale studies point to difficulties with cognitive set-shifting as a basis. Using larger scale studies will lend robustness to these data.

Methodology/Principal Findings

542 participants were included in the dataset as follows: Anorexia Nervosa (AN) n = 171; Bulimia Nervosa (BN) n = 82; Recovered AN n = 90; Healthy controls (HC): n = 199. All completed the Wisconsin Card Sorting Task (WCST), an assessment that integrates multiple measurement of several executive processes concerned with problem solving and cognitive flexibility. The AN and BN groups performed poorly in most domains of the WCST. Recovered AN participants showed a better performance than currently ill participants; however, the number of preservative errors was higher than for HC participants.

Conclusions/Significance

There is a growing interest in the diagnostic and treatment implications of cognitive flexibility in eating disorders. This large dataset supports previous smaller scale studies and a systematic review which indicate poor cognitive flexibility in people with ED.     

Anorexia nervosa and bulimia nervosa.

No definitive therapy exists for anorexia nervosa (AN) or bulimia nervosa (BN). Nevertheless, biologic and psychologic research into these disorders has increased over the last decade. We examine the various drugs available for treatment. Advances in pharmacotherapy for AN have been modest and have reflected efforts either to stimulate hunger and weight gain or to control complications of the starvation process. Food remains the "drug" of choice. Antidepressants have been found to be beneficial in the treatment of BN. The meaning of this in the context of a relation between BN and mood disorders remains unclear, since coexistent depression does not predict a positive response to these drugs. Pharmacotherapy represents a single but important dimension of the management of patients with eating disorders. The optimal integration of drug therapy and psychotherapy and the identification of predictors of a positive response to drugs have yet to be addressed by clinical research.     

Selective Visual Attention during Mirror Exposure in Anorexia and Bulimia Nervosa

Objective

Cognitive theories suggest that body dissatisfaction results from the activation of maladaptive appearance schemata, which guide mental processes such as selective attention to shape and weight-related information. In line with this, the present study hypothesized that patients with anorexia nervosa (AN) and bulimia nervosa (BN) are characterized by increased visual attention for the most dissatisfying/ugly body part compared to their most satisfying/beautiful body part, while a more balanced viewing pattern was expected for controls without eating disorders (CG).

Method

Eye movements were recorded in a group of patients with AN (n = 16), BN (n = 16) and a CG (n = 16) in an ecologically valid setting, i.e., during a 3-min mirror exposure.

Results

Evidence was found that patients with AN and BN display longer and more frequent gazes towards the most dissatisfying relative to the most satisfying and towards their most ugly compared to their most beautiful body parts, whereas the CG showed a more balanced gaze pattern.

Discussion

The results converge with theoretical models that emphasize the role of information processing in the maintenance of body dissatisfaction. Given the etiological importance of body dissatisfaction in the development of eating disorders, future studies should focus on the modification of the reported patterns.     

Binge Eating Behavior in Patients with Eating Disorders

The purpose of this study was to determine whether the objectively observed binge eating behavior of obese subjects meeting the proposed DSM-IV criteria for binge eating disorder would be similar to that observed in patients with bulimia nervosa. Non-obese patients with bulimia nervosa (BN), obese subjects with binge eating disorder (BED), obese and non-obese women without eating disorders were each instructed to binge eat single- and multiple-item meals. In the multiple-item meal, the obese subjects with BED ate significantly more (1515 kcal) than obese subjects without BED (1115 kcal), but they ate less than the normal-weight bulimic patients (2680 kcal). The non-obese controls ate amounts similar to the obese non-binge-eating-disordered group (1093 and 1115.2 kcal, respectively). In the single-item meal, consisting of ice cream, patients with BN ate significantly more than any other group (1307 kcal), while obese subjects with or without binge-eating disorder ate significantly more (762 kcal) than non-obese controls (308 kcal). This study has demonstrated that although both BN and BED are characterized by recurrent episodes of binge eating, quantitatively there appear to be differences between the eating disturbances in the two disorders. Because single- and multiple-item meals differ in external cues, these results also suggest that the obese subjects with BED may be disinhibited by external cues, while obese subjects without BED may be inhibited by external cues.     

The role of leptin and orexins in the dysfunction of hypothalamo-pituitary-gonadal regulation and in the mechanism of hyperactivity in patients with anorexia nervosa

Anorexia nervosa (AN) belongs to a group of eating disorders and is characterized by extreme body weight loss. AN patients show combination of physical, psychological and behavioral disturbances. Neuropeptides partly control energy homeostasis and modulate hormone release. Leptin, a peptide secreted by adipocytes, may influence the interactions between central and peripheral signals. Hypoleptinaemia found in AN is connected with disturbed control of appetite and hormonal dysfunction as well as has implications for the hypothalamo-pituitary-gonadal axis, bone mineral density and physical hyperactivity. Low leptin levels are increased with refeeding. However, the prolonged hypoleptinaemia in weight recovered AN patients may result in persistent hypothalamic amenorrhoea. The hyperactivity has been observed in 31-80 % of AN cases. The mechanisms underlying the hyperactivity found in patients with anorexia nervosa seem to be more complicated as many factors including neuropeptides may be involved. Orexins may affect not only appetite but also behavior and psychophysical activity as they may regulate reproductive and stress hormone secretion, stimulate a variety of stereotypic behaviors including eating and stress reaction, and affect the hypothalamo-pituitary-adrenal (HPA) axis, alter glucocorticoid and catecholamine secretion and activate the sympathetic nervous system. Orexins influence the mechanism regulating arousal and sleep, cardiovascular function, temperature, metabolic rate and locomotive activity. It is worth considering how abnormal activity of hypothalamic neuropeptides or their receptors may play a role in the mechanisms of hyperactivity, disturbed control of appetite and hormonal dysfunction in patients with anorexia nervosa.     

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.     

A Questionnaire Survey of the Type of Support Required by <Emphasis Type="Italic">Yogo</Emphasis> Teachers to Effectively Manage Students Suspected of Having an Eating Disorder

Background

Many studies have focused on the decreasing age of onset of eating disorders (EDs). Because school-age children with EDs are likely to suffer worse physical effects than adults, early detection and appropriate support are important. The cooperation of Yogo teachers is essential in helping these students to find appropriate care. To assist Yogo teachers, it is helpful to clarify the encounter rates (the proportion of Yogo teachers who have encountered ED students) and kinds of requested support (which Yogo teachers felt necessary to support ED students). There are no studies that have surveyed the prevalence rates of ED children by ED type as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5), nor were we able to find any quantitative study surveying the kinds of support Yogo teachers feel helpful to support ED students.

Methods

A questionnaire survey was administered to 655 Yogo teachers working at elementary/junior high/senior high/special needs schools in Chiba Prefecture. The questionnaire asked if the respondents had encountered students with each of the ED types described in DSM-5 (anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), avoidant/restrictive food intake disorder (ARFID), and other types of EDs (Others)), and the kinds of support they felt necessary to support these students. The encounter rates and the kinds of requested were obtained and compared, taking their confidence intervals into consideration.

Results

The encounter rates for AN, BN, BED, ARFID, and Others were 48.4, 14.0, 8.4, 10.7, and 4.6 %, respectively. When classified by school type, AN, BN, BED, and ARFID had their highest encounter rates in senior high schools. Special needs schools had the highest rate for Others. The support most required for all ED types was “a list of medical/consultation institutions.”

Conclusions

Our results have clarified how to support Yogo teachers in the early detection and support of ED students. We found that the encounter rate of AN was the highest, and that it is effective to offer “a list of medical/consultation institutions” to junior and senior high schools where the encounter rates for AN are high.

     

Significant linkage on chromosome 10p in families with bulimia nervosa

Bulimia nervosa (BN) is strongly familial, and additive genetic effects appear to contribute substantially to the observed familiality. In turn, behavioral components of BN, such as self-induced vomiting, are reliably measured and heritable. To identify regions of the genome harboring genetic variants conferring susceptibility to BN, we conducted a linkage analysis of multiplex families with eating disorders that were identified through a proband with BN. Linkage analysis of the entire sample of 308 families yielded a double peak, with the highest nonparametric multipoint maximum LOD score (MLS), of 2.92, on chromosome 10. Given the high heritability of self-induced vomiting and the reliability with which it can be measured, we performed linkage analysis in a subset (n=133) of families in which at least two affected relatives reported a symptom pattern that included self-induced vomiting. The highest MLS (3.39) observed was on chromosome 10, between markers D10S1430 and D10S1423. These results provide evidence of the presence of a susceptibility locus for BN on chromosome 10p. Using simulations, we demonstrate that both of these scores, 2.92 and 3.39, meet the widely accepted criterion for genomewide significance. Another region on 14q meets the criterion for genomewide suggestive linkage, with MLSs of 1.97 (full sample) and 1.75 (subset) at 62 centimorgans from p-ter.     

Effect of nutritional rehabilitation on circulating ghrelin and growth hormone levels in patients with anorexia nervosa

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.     

A questionnaire survey regarding the support needed by <Emphasis Type="Italic">Yogo</Emphasis> teachers to take care of students suspected of having eating disorders (second report)

Background

The lowering of the age of onset and chronicity have been key problems related to eating disorders (EDs). As the proportion of teens in the estimated onset ages has increased, it has become important to detect students with EDs and to clarify how they can be supported. Though epidemiological surveys of Yogo teachers (school nurse/health science teachers) have been conducted to inquire about the number of such students, none of these were done according to ED type based on DSM-5. Thus, we conducted a wide area survey in Japan with the goal of proposing a better framework of support for Yogo teachers in their efforts to care for students with EDs.

Methods

A questionnaire survey organized by ED type (based on DSM-5) was administered to Yogo teachers working at elementary/junior high/senior high/special needs schools in four prefectures of Japan in 2015, and 1,886 responses were obtained. Based on the results, the encounter rates (the proportion of Yogo teachers who had encountered a student with an ED) were calculated, and factors that could affect the rates were examined by logistic regression analysis.

Results

The order of the encounter rates of the ED types was as follows: Anorexia Nervosa (AN)?>?Bulimia Nervosa (BN)?>?Avoidant/Restrictive Food Intake Disorder (ARFID)?>?Binge Eating Disorder (BED)?>?Others. The factors significantly affecting the rates were “location, school type, number of students, experience years, and AN knowledge” for AN, “school type, experience years, and BN knowledge” for BN, “school type, experience years, and BED knowledge” for BED, “location, experience years, and ARFID knowledge” for ARFID, and “school type, experience years, and Others knowledge” for Others.

Conclusions

Because the encounter rate of AN was the highest, providing support for AN would be the most effective. Moreover, one factor that affected the encounter rate of all ED types was ED knowledge. In addition to this, senior high schools had the highest encounter rates for AN, BN and BED, and special needs schools had the highest rates for Others. These findings imply that, in order to detect and support ED students at an early stage, it is necessary to offer knowledge of the most prevalent ED types to Yogo teachers at the corresponding school type.

     

Atypical Antipsychotics as Augmentation Therapy in Anorexia Nervosa

Anorexia nervosa (AN) is a life-threatening and difficult to treat mental illness with the highest mortality rates of any psychiatric disorder. We aimed to garner preliminary data on the real-world use of olanzapine and aripiprazole as augmentation agents of Selective Serotonin Reuptake Inhibitors (SSRIs) in adult inpatients affected by AN. We retrospectively evaluated the clinical charts of patients who were hospitalized between 2012 and 2014. Patients were evaluated upon admission and discharge. We investigated eating symptomatology, and both general and eating psychopathology using: Hamilton Rating Scale for Anxiety, Hamilton Rating Scale for Depression, and Yale-Brown-Cornell Eating Disorders Scale. The charts of 75 patients were included in this study. The sample resulted equally distributed among those receiving SSRIs and either aripiprazole or olanzapine in addition to SSRIs. Notwithstanding a few baseline clinical differences, upon discharge all groups were significantly improved on all measures. Interestingly, aripiprazole showed the greatest effectiveness in reducing eating-related preoccupations and rituals with a large effect size. The body of evidence on medication management in AN is in dismal condition. Augmentation therapy is a well-established approach to a variety of mental disorders and it is often used in every-day clinical practice with patients affected by AN as well. Nevertheless, to date very little data is available on this topic. Results from our sample yielded promising results on the effectiveness of aripiprazole augmentation in reducing eating-related obsessions and compulsions. Randomized controlled trials are warranted to confirm these encouraging findings.     

Ghrelin concentrations and cardiac vagal tone are decreased after pharmacologic and cognitive-behavioral treatment in patients with bulimia nervosa

Patients with bulimia nervosa (BN) have bulimic and depressive symptoms, which have been associated with abnormalities in the neuroendocrine and vagal systems. Subjects included twenty-four female drug-free outpatients with BN that were selected from patients seeking treatment for eating behavior in our hospital along with twenty-five age-matched healthy females who served as controls. We investigated ghrelin and leptin levels, cardiac vagal tone and sympathovagal balance, frequency of sets of binge-eating and vomiting episodes per week and the Profile of Mood States (POMS) depression scale in BN before and after a 16-week administration of the serotonin selective reuptake inhibitor (SSRI) paroxetine combined with cognitive-behavioral therapy. Compared to controls, the BN group had higher ghrelin levels and resting cardiac vagal tone, and lower leptin levels and resting cardiac sympathovagal balance before treatment, although there was a significant difference between the two groups for the body mass index (BMI). The elevated ghrelin levels (301.7 +/- 18.9 pmol/l, mean +/- SEM vs. 202.8 +/- 15.6 pmol/l, P < 0.01), cardiac vagal tone (2246.4 +/- 335.5 ms(2) vs. 1128.5 +/- 193.3 ms(2), P < 0.01), frequency of sets of binge-eating and purging episodes and T scores for the POMS depression scale were all significantly decreased after treatment despite similar BMI, percent body fat and leptin levels. In close association with cardiac vagal function and ghrelin recoveries, abnormal eating behavior and depressive symptoms improved, indicating the usefulness of these indexes in the assessment of clinical condition and therapeutic efficacy in BN.     

The bombesin/gastrin releasing peptide receptor antagonist RC-3095 blocks apomorphine but not MK-801-induced stereotypy in mice

Bombesin (BN)-like peptides might be involved in the pathogenesis of neuropsychiatric disorders such as schizophrenia. Stereotyped behaviors induced by the dopamine receptor agonist apomorphine or the N-methyl-D-aspartate glutamate receptor antagonist dizocilpine (MK-801) in rodents have been proposed as animal models of schizophrenic psychosis. In the present study we evaluated the effects of the BN/gastrin-releasing peptide receptor (GRP) antagonist (D-Tpi6, Leu13 psi[CH2NH]-Leu14) bombesin (6-14) (RC-3095) on apomorphine and MK-801-induced stereotyped behavior in mice. An intraperitoneal (i.p.) injection of RC-3095 (1.0, 10.0 or 100.0 mg/kg) blocked apomorphine-induced stereotypy. The inhibitory effect of RC-3095 on apomorhine-induced stereotypy was similar to that induced by haloperidol (0.5 mg/kg). RC-3095 did not affect stereotyped behavior induced by MK-801 (0.5 mg/kg). The results provide the first evidence that BN/GRP receptor antagonism blocks stereotyped behavior induced by a dopamine agonist. Together with previous evidence, the present study indicates that the BN/GRP receptor can be considered a drug target in the investigation of potential new agents for treating neuropsychiatric disorders.     

Plasma intact fibroblast growth factor 23 levels in women with bulimia nervosa: A cross-sectional pilot study

Fibroblast growth factor (FGF) 23, a circulating 26-kDa peptide produced by osteogenic cells, is a novel phosphaturic factor. In our previous study, binge-eating/purging type anorexia nervosa (AN-BP) patients had elevated plasma intact FGF23 (iFGF23) levels, while restricting type (AN-R) patients had plasma iFGF23 levels similar to healthy controls. Although bulimia nervosa (BN) patients as well as some patients with AN-BP regularly engage in binge eating, there have been no studies regarding plasma iFGF23 levels in BN patients. Therefore, this study was performed to determine plasma iFGF23 concentrations in BN patients and healthy controls. The study population consisted of 13 female BN patients and 11 healthy female controls. Blood samples were collected from all subjects after overnight fasting. Plasma iFGF23 was measured using an ELISA kit in a cross-sectional manner. The two-tailed Mann-Whitney U-test was used to assess differences between BN patients and healthy controls. In addition, BN patients were divided into two groups based on questionnaire-reported binge eating frequency immediately prior to participation in this study: high frequency of binge eating (once a week or more; HF group; n = 8) and low frequency of binge eating (less than once a week; LF group; n = 5). Two-tailed Mann-Whitney U-test with Bonferroni's correction was performed after the Kruskal-Wallis test to assess differences between HF group, LF group, and healthy controls. Median (quartiles) plasma iFGF23 levels were greater in BN patients (35.5 [14.8-65.0] pg/ml) than in controls (3.8 [not detected-5.3] pg/ml; p = 0.002). In addition, median (quartiles) plasma iFGF23 levels were greater in the HF group (62.3 [44.4-73.4] pg/ml) than in controls (p < 0.001) and in the LF group (12.9 [not detected-30.3] pg/ml; p = 0.011), while there were no differences between the LF group and controls (p = 0.441). This is the first study to show that BN patients have elevated plasma iFGF23 levels. Moreover, this study showed that BN patients with a high frequency of binge eating have elevated plasma iFGF23 levels, while iFGF23 levels are similar to healthy controls in those with a low frequency of binge eating. Plasma iFGF23 level may be a suitable indicator of binge eating in BN patients.