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Michael W Schwartz - One of the best experts on this subject based on the ideXlab platform.
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cancer induced Anorexia and malaise are mediated by cgrp neurons in the parabrachial nucleus
Nature Neuroscience, 2017Co-Authors: Carlos A Campos, Richard D Palmiter, Anna J Bowen, Sung Han, Brent E Wisse, Michael W SchwartzAbstract:Anorexia is a common manifestation of chronic diseases, including cancer. Here we investigate the contribution to cancer Anorexia made by calcitonin gene-related peptide (CGRP) neurons in the parabrachial nucleus (PBN) that transmit anorexic signals. We show that CGRPPBN neurons are activated in mice implanted with Lewis lung carcinoma cells. Inactivation of CGRPPBN neurons before tumor implantation prevents Anorexia and loss of lean mass, and their inhibition after symptom onset reverses Anorexia. CGRPPBN neurons are also activated in Apcmin/+ mice, which develop intestinal cancer and lose weight despite the absence of reduced food intake. Inactivation of CGRPPBN neurons in Apcmin/+ mice permits hyperphagia that counteracts weight loss, revealing a role for these neurons in a 'nonanorexic' cancer model. We also demonstrate that inactivation of CGRPPBN neurons prevents lethargy, anxiety and malaise associated with cancer. These findings establish CGRPPBN neurons as key mediators of cancer-induced appetite suppression and associated behavioral changes.
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evidence that intestinal glucagon like peptide 1 plays a physiological role in satiety
Endocrinology, 2009Co-Authors: D J L Williams, Denis G Baskin, Michael W SchwartzAbstract:A physiological role in satiety is proposed for glucagon-like peptide-1 (GLP-1), secreted by the distal intestine in response to ingested nutrients. Here we report that in rats, ip injection of the GLP-1 receptor (GLP-1-R) antagonist exendin 9-39 (Ex9) elicited hyperphagia, but only at times of day when intake is otherwise low. Furthermore, ip administration of Ex9 attenuated satiety induced by either a voluntarily consumed sucrose meal (by 100%) or an intragastric glucose load (by 40%). To determine whether these effects involve blockade of GLP-1-R in brain or at a peripheral site, we injected Ex9 either centrally (into the third ventricle) or peripherally (ip) prior to GLP-1 injected either centrally or peripherally. Anorexia induced by peripheral GLP-1 was fully blocked by peripheral, but not central, pretreatment with Ex9, whereas the opposite was true for anorexic effect of central GLP-1. Thus, ip Ex9 appears to attenuate satiety via peripheral GLP-1-R blockade. Finally, Anorexia induced by ip injection of exendin-4 (a GLP-1-R agonist) was due to both reduced meal size and increased duration between meals. We conclude that GLP-1 released from the intestine in response to ingested nutrients is a physiologically active satiety signal.
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Reversal of cancer Anorexia by blockade of central melanocortin receptors in rats.
Endocrinology, 2001Co-Authors: Brent E Wisse, Michael W Schwartz, R. Scott Frayo, David E. CummingsAbstract:Anorexia is a debilitating manifestation of many malignancies. The etiology of cancer Anorexia is poorly understood, and effective treatment options are limited. To investigate the role of central melanocortin receptor signaling in the pathogenesis of cancer Anorexia, we assessed the effects on food intake of the melanocortin receptor antagonist SHU9119 administered into the third cerebral ventricle of Lobund-Wistar rats that were anorexic from prostate cancer. In anorexic tumor-bearing rats, daily treatment with SHU9119 (0.35 nmol, intracerebroventricularly) increased food intake from 71 ± 3% to 110 ± 6% of preanorectic baseline and caused significant weight gain (13 ± 5 vs. 5 ± 1 g/3 d, SHU9119 vs. baseline in tumor-bearing rats). In control rats pair-fed to the intake of tumor-bearing animals, SHU9119 was ineffective at increasing food intake. The specificity of the SHU9119 feeding response was assessed using two other orexigenic peptides, NPY and the novel hormone ghrelin. Treatment of tumor-bearing r...
Chia Huang - One of the best experts on this subject based on the ideXlab platform.
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investigating the effectiveness safety and tolerability of quetiapine in the treatment of Anorexia nervosa in young people a pilot study
Wiadomosci Psychiatryczne, 2012Co-Authors: Andrew Court, Claudia Mulder, Melissa Kerr, Hok Pan Yuen, Melissa Boasman, Sherilyn Goldstone, Judith Fleming, Susan Weigall, Harry Derham, Chia HuangAbstract:To investigate the safety and tolerability of the atypical antipsychotic quetiapine in Anorexia nervosa patients, and to determine the effect of quetiapine treatment on anorexic psychopathology and other key outcome measures including weight and body image, we conducted a naturalistic, open-label, 12-week randomized controlled trial of low-dose (100e400 mg/day) quetiapine treatment versus treatment as usual in 33 Anorexia nervosa patients from our Eating Disorder Clinics. To monitor the effects of treatment over the medium term, the participants were then followed up with assessment visits at 6 and 12 months after the end of the treatment phase. Low-dose quetiapine treatment resulted in both psychological and physical improvements, with minimal associated side-effects. Given the overall trend toward improvement that we observed, quetiapine appears to be a promising candidate for the treatment of Anorexia nervosa. Further large-scale placebo-controlled clinical trials will be necessary to fully evaluate the benefits of quetiapine treatment for this disorder.
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investigating the effectiveness safety and tolerability of quetiapine in the treatment of Anorexia nervosa in young people a pilot study
Journal of Psychiatric Research, 2010Co-Authors: Andrew Court, Claudia Mulder, Melissa Kerr, Hok Pan Yuen, Melissa Boasman, Sherilyn Goldstone, Judith Fleming, Susan Weigall, Harry Derham, Chia HuangAbstract:To investigate the safety and tolerability of the atypical antipsychotic quetiapine in Anorexia nervosa patients, and to determine the effect of quetiapine treatment on anorexic psychopathology and other key outcome measures including weight and body image, we conducted a naturalistic, open-label, 12-week randomized controlled trial of low-dose (100-400 mg/day) quetiapine treatment versus treatment as usual in 33 Anorexia nervosa patients from our Eating Disorder Clinics. To monitor the effects of treatment over the medium term, the participants were then followed up with assessment visits at 6 and 12 months after the end of the treatment phase. Low-dose quetiapine treatment resulted in both psychological and physical improvements, with minimal associated side-effects. Given the overall trend toward improvement that we observed, quetiapine appears to be a promising candidate for the treatment of Anorexia nervosa. Further large-scale placebo-controlled clinical trials will be necessary to fully evaluate the benefits of quetiapine treatment for this disorder.
Walter H Kaye - One of the best experts on this subject based on the ideXlab platform.
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controlled family study of Anorexia nervosa and bulimia nervosa evidence of shared liability and transmission of partial syndromes
American Journal of Psychiatry, 2000Co-Authors: Michael Strober, Roberta Freeman, Carlyn Lampert, Jane Diamond, Walter H KayeAbstract:OBJECTIVE: Lifetime rates of full and partial Anorexia nervosa and bulimia nervosa were determined in first-degree relatives of diagnostically pure proband groups and relatives of matched, never-ill comparison subjects. METHOD: Rates of each eating disorder were obtained for 1,831 relatives of 504 probands on the basis of personal structured clinical interviews and family history. Best-estimate diagnoses based on all available information were rendered without knowledge of proband status and pedigree identity. Only definite and probable diagnoses were considered. RESULTS: Whereas Anorexia nervosa was rare in families of the comparison subjects, full and partial syndromes of Anorexia nervosa aggregated in female relatives of both anorexic and bulimic probands. For the full syndrome of Anorexia nervosa, the relative risks were 11.3 and 12.3 in female relatives of anorexic and bulimic probands, respectively. Bulimia nervosa was more common than Anorexia nervosa in female relatives of comparison subjects, but...
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a controlled family study of Anorexia nervosa and bulimia nervosa psychiatric disorders in first degree relatives and effects of proband comorbidity
Archives of General Psychiatry, 1998Co-Authors: Lisa R Lilenfeld, Walter H Kaye, Katherine Plotnicov, Catherine G Greeno, Cynthia M. Bulik, Kathleen R Merikangas, Christine Pollice, Michael Strober, Linda M NagyAbstract:Background We used contemporary family-epidemiological methods to examine patterns of comorbidity and familial aggregation of psychiatric disorders for Anorexia and bulimia nervosa. Methods Direct interviews and blind best-estimate diagnostic procedures were used with diagnostically "pure" groups of probands with eating disorders and a matched control group. Lifetime prevalence rates of eating disorders, mood disorders, substance use disorders, anxiety disorders, and selected personality disorders were determined in female probands with restricting Anorexia nervosa (n=26) or bulimia nervosa (n=47), control women (n=44), and first-degree biological relatives (n=460). Results Relatives of anorexic and bulimic probands had increased risk of clinically subthreshold forms of an eating disorder, major depressive disorder, and obsessive-compulsive disorder. Familial aggregation of major depressive disorder and obsessive-compulsive disorder was independent of that of Anorexia nervosa and bulimia nervosa. These relatives also had increased risk of other anxiety disorders, but the mode of familial transmission was not clear-cut. The risk of substance dependence was elevated among relatives of bulimic probands compared with relatives of anorexic probands, and familial aggregation was independent of that of bulimia nervosa. The risk of obsessive-compulsive personality disorder was elevated only among relatives of anorexic probands, and there was evidence that these 2 disorders may have shared familial risk factors. Conclusions There may be a common familial vulnerability for Anorexia nervosa and bulimia nervosa. Major depressive disorder, obsessive-compulsive disorder, and substance dependence are not likely to share a common cause with eating disorders. However, obsessional personality traits may be a specific familial risk factor for Anorexia nervosa.
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relationship of depression anxiety and obsessionality to state of illness in Anorexia nervosa
International Journal of Eating Disorders, 1997Co-Authors: Christine Pollice, Walter H Kaye, Catherine G Greeno, Theodore E WeltzinAbstract:Objective Depression, anxiety, and obsessionality frequently are present in underweight, malnourished patients with Anorexia nervosa. It is less certain if these symptoms persist after recovery. Thus, we assessed these symptoms in anorexic women at three states of illness (underweight, short-term weight restored, and long-term weight restored) in comparison to a group of healthy women. Method: We used standardized self- and trained rater instruments to assess depression (Hamilton Depression Rating Scale and Beck Depression Inventory), anxiety (Spielberger State-Trait Anxiety Inventory and Hamilton Anxiety Rating Scale), and obsessions and compulsions (Yale-Brown Obsessive Compulsive Scale). Results: A similar pattern was found for all symptoms. That is, scores for depression, anxiety, and obsessionality were most elevated in the underweight state. These symptoms improved with weight restoration. However, milder but significantly elevated symptoms persisted in long-term weight-restored anorexic women compared to healthy control women. Discussion: These data suggest that malnutrition intensifies the severity of depression, anxiety, and obsessionality in Anorexia nervosa. However, the fact that mild to moderate symptoms persisted after long-term weight restoration raises the possibility that such behaviors are related to the pathogenesis of this illness. © 1997 by John Wiley & Sons, Inc. Int J Eat Disord 21: 367–376, 1997.
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persistent perfectionism symmetry and exactness after long term recovery from Anorexia nervosa
American Journal of Psychiatry, 1995Co-Authors: Nalini M Srinivasagam, Walter H Kaye, Katherine Plotnicov, Catherine G Greeno, Theodore E Weltzin, Radhika RaoAbstract:Objective : It is well recognized that patients with Anorexia nervosa have perfectionistic and obsessive behaviors. This study investigated whether such behaviors persist after recovery. Method : Twenty subjects who had recovered from Anorexia nervosa were recruited for the study. They had been at normal weight and their menses had been regular for more than a year. These subjects were compared with 16 healthy women with the use ofthe Eating Disorder Inventory, the Frost Multidimensional Perfectionism Scale, and the Yale-Brown Obsessive Compulsive Scale. Results : The recovered anorexic patients had significantly higher scores than the comparison women on the measures of perfectionism on the Eating Disorder Inventory and on overall perfectionism on the Frost scale. Moreover, the recovered patients had higher scores on the Yale-Brown scale, with target symptoms suggesting that many had specific concerns with symmetry and exactness. Conclusions : Certain characteristics of Anorexia nervosa, such as a need for order and precision, persist after good outcome and recovery, raising the question of whether these behaviors are traits that contribute to the pathogenesis of this illness.
M B Leshem - One of the best experts on this subject based on the ideXlab platform.
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the effect of 5 hydroxytryptophan on food intake and on the anorexic action of amphetamine and fenfluramine
Journal of Pharmacy and Pharmacology, 2011Co-Authors: John E Blundell, M B LeshemAbstract:5-Hydroxytryptophan (5-HTP), amphetamine and fenfluramine suppressed food intake in normal rats and in animals with lesions of the lateral hypothalamus. The anorexic effect of amphetamine was reduced in lesioned animals compared with controls while the effect of 5-HTP like that of fenfluramine was increased. When administered in conjunction with the anorexic drugs, 5-HTP markedly potentiated the anorexic effect of amphetamine in both control and lesioned animals. However, 5-HTP potentiated fenfluramine Anorexia only in lesioned rats. These findings provide further evidence for the role of 5-hydroxytryptamine (5-HT), in the anorexic effect of fenfluramine, and suggest that a 5-HT mechanism, inhibitory for feeding, produces particularly severe suppression of food intake in rats with lateral hypothalamic lesions.
Esther M Cohentovee - One of the best experts on this subject based on the ideXlab platform.
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the estimation of body mass index and physical attractiveness is dependent on the observer s own body mass index
Proceedings of The Royal Society B: Biological Sciences, 2000Co-Authors: Martin J Tovee, Joanne L Emery, Esther M CohentoveeAbstract:A disturbance in the evaluation of personal body mass and shape is a key feature of both Anorexia and bulimia nervosa. However, it is uncertain whether overestimation is a causal factor in the development of these eating disorders or is merely a secondary effect of having a low body mass. Moreover, does this overestimation extend to the perception of other people's bodies? Since body mass is an important factor in the perception of physical attractiveness, we wanted to determine whether this putative overestimation of self body mass extended to include the perceived attractiveness of others. We asked 204 female observers (31 anorexic, 30 bulimic and 143 control) to estimate the body mass and rate the attractiveness of a set of 25 photographic images showing people of varying body mass index (BMI). BMI is a measure of weight scaled for height (kg m(- 2)). The observers also estimated their own BMI. Anorexic and bulimic observers systematically overestimated the body mass of both their own and other people's bodies, relative to controls, and they rated a significantly lower body mass to be optimally attractive. When the degree of overestimation is plotted against the BMI of the observer there is a strong correlation. Taken across all our observers, as the BMI of the observer declines, the overestimation of body mass increases. One possible explanation for this result is that the overestimation is a secondary effect caused by weight loss. Moreover, if the degree of body mass overestimation is taken into account, then there are no significant differences in the perceptions of attractiveness between anorexic and bulimic observers and control observers. Our results suggest a significant perceptual overestimation of BMI that is based on the observer's own BMI and not correlated with cognitive factors, and suggests that this overestimation in eating-disordered patients must be addressed directly in treatment regimes.