Ghrelin: A Link between Eating Disorders,Obesity and Reproduction

Abstract

Ghrelin, a 28-amino acid acylated peptide predominantly produced by the stomach, displays strong GH-releasing activity mediated by the hypothalamic-pituitary GH secretagogues (GHS) receptors (GHS-R) which had been shown specific for a family of synthetic, orally active molecules known as GHS. However, ghrelin and GHS, acting on central and peripheral receptors, also exert other actions. These include influence on pituitary functions, orexigenic action, influence on exocrine and endocrine gastro-entero-pancreatic functions, cardiovascular and anti-proliferative effects. In particular, the effect of ghrelin in promoting food intake and modulating energy metabolism strongly suggested that ghrelin has a key role in managing the neuroendocrine and metabolic response to starvation and that could be involved in the pathogenesis and/or in the metabolic and neuro-hormonal alterations of obesity and eating disorders. Although specific alterations in ghrelin secretion and/or action in obesity and anorexia nervosa (AN) have already been reported, the possibility that ghrelin analogues acting as agonists or antagonists has clinical perspectives for treatment of eating disorders presently remains a dream.     

Recognition and therapy of eating disorders in young women in primary care

Objective To evaluate the prevalence of eating disorders (ED) in a general population sample of young German women, compare those to primary care diagnoses, and investigate their medical treatments.Methods In a prospective epidemiological study, a representative sample of young women (n=1555, between 18 and 25 years of age) was questioned twice during a structured psychological interview (F-DIPS) for mental disorders according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). At the same time, personal health insurance data were recorded and primary care physicians diagnoses and payments for services rendered were analyzed.Results The lifetime prevalence of eating disorders was 3.3% (2.3% anorexia nervosa, 1.1% bulimia nervosa). The primary care physicians diagnosed eating disorders in only about 20% of the women concerned. Eating disorders were often overlooked, although physicians detected physical and mental complaints (e.g., menstrual cycle disorders, abnormal weight loss, flatulence, depression, anxiety disorders), which are closely related to eating disorders. If the primary care physicians had diagnosed eating disorders, they mostly recommended psychotherapeutic treatment as the only measure, or in combination with pharmacological therapy.Conclusion The study indicates that primary care physicians need better training, particularly in diagnostic procedures for eating disorders. Screening methods and systematic assessment might be helpful in improving the detection of eating disorders in primary care     

The Role of the Gut Microbiome,Immunity, and Neuroinflammation in the Pathophysiology of Eating Disorders

There is a growing recognition that both the gut microbiome and the immune system are involved in a number of psychiatric illnesses, including eating disorders. This should come as no surprise, given the important roles of diet composition, eating patterns, and daily caloric intake in modulating both biological systems. Here, we review the evidence that alterations in the gut microbiome and immune system may serve not only to maintain and exacerbate dysregulated eating behavior, characterized by caloric restriction in anorexia nervosa and binge eating in bulimia nervosa and binge eating disorder, but may also serve as biomarkers of increased risk for developing an eating disorder. We focus on studies examining gut dysbiosis, peripheral inflammation, and neuroinflammation in each of these eating disorders, and explore the available data from preclinical rodent models of anorexia and binge-like eating that may be useful in providing a better understanding of the biological mechanisms underlying eating disorders. Such knowledge is critical to developing novel, highly effective treatments for these often intractable and unremitting eating disorders.     

A virtual issue highlighting animal studies of eating disorders as valuable tools for examining neurobiological underpinnings and treatment of eating disorders

While studies in humans suggest a role for psychosocial factors as well as biological and genetic processes in the development of eating disorders, the specific etiologic mechanisms remain largely unknown. In this virtual issue, we present a collection of 14 archived articles from the International Journal of Eating Disorders to highlight the utility of animal studies of eating disorders to advance our understanding of eating disorder etiology. Selected articles establish animal studies as valid tools to study disordered eating behavior, offer insight into potential neurobiological mechanisms, and highlight novel targets for future pharmacological treatments. Clinical implications of each article's findings are included to demonstrate the translational value of animal studies for the eating disorders field. We hope that the exciting concepts and findings in this issue inspire future animal studies of eating disorders.     

Health service utilization for eating disorders: findings from a community-based study

BACKGROUND: Prior use of health services was examined in a community sample of women with bulimic-type eating disorders. METHOD: Participants (n = 159) completed a structured interview for the assessment of eating disorder psychopathology as well as questions concerning treatment-seeking and type of treatment received. RESULTS: Whereas a minority (40.3%) of participants had received treatment for an eating problem, most had received treatment for a general mental health problem (74.2%) and/or weight loss (72.8%), and all had used one or more self-help treatments. Where treatment was received for an eating or general mental health problem, this was from a primary care practitioner in the vast majority of cases. Only half of those participants who reported marked impairment associated with an eating problem had ever received treatment for such a problem and less than one in five had received such treatment from a mental health professional. CONCLUSION: Women with bulimic-type eating disorders rarely receive treatment for an eating problem, but frequently receive treatment for a general mental health problem and/or for weight loss. The findings underscore the importance of programs designed to improve the detection and management of eating disorders in primary care.     

Review of the prevalence and incidence of eating disorders

OBJECTIVE: To review the literature on the incidence and prevalence of eating disorders. METHODS: We searched Medline using several key terms relating to epidemiology and eating disorders and we checked the reference lists of the articles that we found. Special attention has been paid to methodologic problems affecting the selection of populations under study and the identification of cases. RESULTS: An average prevalence rate for anorexia nervosa of 0.3% was found for young females. The prevalence rates for bulimia nervosa were 1% and 0.1% for young women and young men, respectively. The estimated prevalence of binge eating disorder is at least 1%. The incidence of anorexia nervosa is 8 cases per 100,000 population per year and the incidence of bulimia nervosa is 12 cases per 100,000 population per year. The incidence of anorexia nervosa increased over the past century, until the 1970s. DISCUSSION: Only a minority of people who meet stringent diagnostic criteria for eating disorders are seen in mental health care.     

Sensor technology implementation for research,treatment, and assessment of eating disorders

Sensor technology has made huge technological advances in the past decade. Many sensor technologies (e.g., wearable wristbands) have been integrated into health research with the ability to substantially improve health outcomes and reduce health care costs. Despite the rapid technological developments in sensor technology, little research has examined sensor technology in eating disorders (EDs). The overarching aim of the current article is to briefly review the literature on sensor technology and health outcomes, including EDs, and discuss several potential ideas for the application of sensor technology in the treatment, assessment, and diagnosis of EDs. We will also present data from a feasibility case study with an ED participant and healthy control providing a brief example of how wearable sensor technology might be implemented in ED research. Overall, we will discuss how sensor technology could be used to improve treatment and assessment of EDs and represents an idea in need of more research in the ED field.     

College students' mental models for recognizing anorexia and bulimia nervosa

Knowledge about eating disorders influences lay people's ability to recognize individuals with anorexia nervosa (AN) and bulimia nervosa (BN) and refer them to professional treatment. We assessed mental models (stored knowledge) of AN and BN in 106 college students. Results indicated that most students have general, but not specific, information about AN and BN's symptoms, consequences, causes, duration, and cures. They also believe that people with eating disorders tend to be young, White women. These findings suggest that lay recognition of eating disorders may be based primarily on observations of dysfunctional eating behaviors and therefore facilitated by additional knowledge.     

Are improvements in shame and self‐compassion early in eating disorders treatment associated with better patient outcomes?

Compassion‐focused therapy (CFT; Gilbert, 2005, 2009) is a transdiagnostic treatment approach focused on building self‐compassion and reducing shame. It is based on the theory that feelings of shame contribute to the maintenance of psychopathology, whereas self‐compassion contributes to the alleviation of shame and psychopathology. We sought to test this theory in a transdiagnostic sample of eating disorder patients by examining whether larger improvements in shame and self‐compassion early in treatment would facilitate faster eating disorder symptom remission over 12 weeks. Participants were 97 patients with an eating disorder admitted to specialized day hospital or inpatient treatment. They completed the Eating Disorder Examination‐Questionnaire, Experiences of Shame Scale, and Self‐Compassion Scale at intake, and again after weeks 3, 6, 9, and 12. Multilevel modeling revealed that patients who experienced greater decreases in their level of shame in the first 4 weeks of treatment had faster decreases in their eating disorder symptoms over 12 weeks of treatment. In addition, patients who had greater increases in their level of self‐compassion early in treatment had faster decreases in their feelings of shame over 12 weeks, even when controlling for their early change in eating disorder symptoms. These results suggest that CFT theory may help to explain the maintenance of eating disorders. Clinically, findings suggest that intervening with shame early in treatment, perhaps by building patients' self‐compassion, may promote better eating disorders treatment response. (Int J Eat Disord 2014; 47:54–64)     

Nutritional counselling in bulimia nervosa. A case study

This case study outlines a strategy for the dietetic management of individuals with eating disorders. It shows the progress made by a young woman with bulimia nervosa, who, with the assistance of dietary advice, was able to reduce the occurrence of binge-eating and purging, and normalize her eating behaviour.     

Anorexia nervosa and Raynaud's phenomenon: a case report

OBJECTIVE: To describe and discuss potential relationships between anorexia nervosa (AN) and Raynaud's phenomenon, the course and concurrent treatment of these two disorders as they appeared simultaneously, and a potential treatment modification entailed in such concurrent therapies. BACKGROUND: Although Raynaud's phenomenon has been described during the course of AN, the associations and interactions between these two conditions are not clear. METHOD: We report the medical workup, treatment, and outcomes in a 19-year old female patient who developed Raynaud's phenomenon following the onset of AN. RESULTS: After treatment with nutritional rehabilitation, counseling, and individual and group therapy, the patient's weight, eating disorder-related behaviors, and attitudes improved significantly. Raynaud's related symptoms improved, following treatment with a calcium channel blocker and antiaggregant therapy. In conjunction with nutritional efforts to treat the patient's long-standing amenorrhea and osteopenia, the treatment team elected to also administer estrogen hormone in addition to oral calcium and vitamin D supplementation. Since oral contraceptives are to be avoided in patients with Raynaud's phenomenon who show clinical findings suggesting connective tissue disorder, the treatment team elected to treat this patient with transdermal hormone replacement therapy. CONCLUSION: The co-occurrence of AN and Raynaud's phenomenon merits close and persistent follow-up by a multidisciplinary team and may lead to alterations of usual therapeutic approaches.     

Stigmatization toward People with Anorexia Nervosa,Bulimia Nervosa,and Binge Eating Disorder: A Scoping Review

Research about stigmatization in eating disorders (EDs) has highlighted stereotypes, prejudices, and discrimination against people with EDs, as well as their harmful effects on them, including self-stigma and a difficult recovery process. Whereas a recent review focused on the consequences of ED stigma, our work aimed to provide a broader synthesis of ED stigma, including its consequences, but also its content and distribution. More precisely, we focused on three EDs—namely, anorexia nervosa, bulimia nervosa, and binge eating disorder. Based on a systematic search of four major databases in psychology, the present scoping review includes 46 studies published between 2004 and 2021. We did not conduct any quality assessment of the studies included, because our aim was to provide a wide-ranging overview of these topics instead of an appraisal of evidence answering a precise research question. The review confirmed the existence of a common ED stigma: all individuals affected by EDs reviewed here were perceived as responsible for their situation, and elicited negative emotions and social distance. However, our review also depicted a specific stigma content associated with each ED. In addition, the demographic characteristics of the stigmatizing individuals had a notable influence on the extent of ED stigma: men, young adults, and low-income individuals appeared to be the most stigmatizing toward individuals with EDs. It is important to note that ED stigma had a negative effect on individuals’ eating disorders, psychological wellbeing, and treatment-seeking behavior. There is an urgent need for further research on the adverse effects of ED stigma and its prevention.     

"Not all my fault": Genetics, stigma, and personal responsibility for women with eating disorders

Medical researchers and clinicians increasingly understand and present eating disorders (anorexia and bulimia nervosa) as biologically-based psychiatric disorders, with genetic risk factors established by high heritability estimates in twin studies. But there has been no research on interpretation of genetic involvement by people with eating disorders, who may hold other views. Their interpretations are particularly important given the frequent presumption that biogenetic framing will reduce stigma, and recent findings that it exacerbates stigma for other mental illnesses. To identify implications of genetic framing in eating disorders, I conducted semi-structured interviews with 50 US women with a history of eating disorders (half recovered, half in treatment; interviewed 2008-9 in the USA). Interviews introduced the topic of genetics, but not stigma per se. Analysis followed the general principles of grounded theory to identify perceived implications of genetic involvement; those relevant to stigma are reported here. Most anticipated that genetic reframing would help reduce stigma from personal responsibility (i.e., blame and guilt for eating disorder as ongoing choice). A third articulated ways it could add stigma, including novel forms of stigma related to genetic-essentialist effacing of social factors. Despite welcoming reductions in blame and guilt, half also worried genetic framing could hamper recovery, by encouraging fatalistic self-fulfilling prophecies and genetic excuses. This study is the first to elicit perceptions of genetic involvement by those with eating disorders, and contributes to an emerging literature on perceptions of psychiatric genetics by people with mental illness.     

Why is premorbid BMI consistently elevated in clinical samples,but not in risk factor samples,of individuals with eating disorders?

Body image disturbance is widely viewed as contributing to the development and maintenance of disordered eating. Yet this perspective is not inconsistent with the possibility that elevated premorbid BMIs also increase the risk of developing eating disorders. Research examining whether actual body size may play a role in eating disorder development reveals a curious pattern of findings. Few prospective risk factor studies conducted with community-based samples found a relationship between premorbid BMI and subsequent eating disorder pathology whereas retrospective research conducted with clinical samples indicates a consistent pattern of elevated premorbid BMIs relative to population norms or control groups. This study documents these disparate findings, considers potential explanations for them and proposes further study of premorbid BMI as a factor contributing to the psychopathology of eating disorders, particularly among those who come to the attention of treatment providers.     

Telehealth transition in a comprehensive care unit for eating disorders: Challenges and long-term benefits

The 2019 novel coronavirus disease (COVID-19) pandemic has forced many eating disorder medical stabilization units to consider adjustments that uphold both the quality of care delivered to patients while also observing social distancing public health directives for patients and staff. To date, inpatient facilities for eating disorders (both medical stabilization units and higher level of care facilities) have not needed to consider how to translate services to electronic platforms, given that most of these programs have in-person staff. We outline our transition to telehealth broadly, emphasizing some unexpected benefits of using telehealth services that we plan on integrating into our work-flow post COVID-19. These may be useful for other higher level of care eating disorder programs, including medical stabilization units, residential, partial hospitalization, and intensive outpatient programs. We also highlight aspects of transition that have been more challenging for this particular patient population, warranting the need for in-person services.     

Severe and enduring anorexia nervosa: Update and observations about the current clinical reality

Several objectives underlie the current article. First, to review historical diagnostic issues and clinical strategies for treating SE-AN. Second, to provide an overview of recent evidence informed strategies and clinical innovations for the treatment of SE-AN. Third, based on the authors' collective clinical and research experience, we offer eight observations that we believe capture the current clinical experience of patients with SE-AN. Some of these observations represent empirically testable hypotheses, but all are designed to generate a meaningful discussion about the treatment of this group of individuals with eating disorders. Finally, we hope to call clinicians, scientists, professional organizations, advocates, and policy makers to action to attend to critical issues related to the care of individuals with SE-AN. We believe that an international discussion could clarify areas of need for these patients and identify opportunities for clinical innovation that would enhance the lives of individuals with SE-AN and their families.     

Severe and enduring anorexia nervosa: No easy solutions

There is currently no evidence-based definition of severe and enduring anorexia nervosa (SE-AN) with which to reliably inform clinical practice and research. Indeed, data on the effect of AN severity and duration on treatment outcome are inconsistent. A large group of patients with SE-AN are repeatedly unsuccessfully managed with the available eating disorders treatments and have no access to adequate treatment for their illness. Cognitive behavioral therapy (CBT) adapted for SE-AN has been designed to enhance quality of life and reduce harm rather than promoting weight gain in such patients, and has had some success. However, a percentage of patients with SE-AN achieves remission, or at least returns to a normal weight range, with available evidence-based treatments for eating disorders, such as enhanced CBT (CBT-E). It would therefore be worth conducting a large-scale randomized controlled trial comparing CBT adapted for SE-AN with CBT-E to assess their relative acceptability; efficacy, including their effect on quality of life and medical stability; cost-effectiveness; and the treatment response moderators that might allow better matching of patients with SE-AN to a treatment oriented either to harm reduction or to change.     

Factors Associated with Underweight,Overweight, and Eating Disorders in Young Korean Women: A Population-Based Study

Both underweight (UW) and overweight (OW) conditions are problematic in young women. The aim of this study was to examine the factors associated with extreme weight status and eating disorders (EDs) in young Korean women. A total of 808 women (mean age 22.3 ± 3.4 years) participated, including 144 with UW [Body Mass Index (BMI) < 18.5kg/m²], 364 with NW, and 137 with OW or obesity (BMI ≥ 25kg/m²), and 63 patients with anorexia nervosa (AN) and 100 with bulimia nervosa (BN). Participants completed questionnaires regarding nutrients consumed, eating behaviors, health behaviors, body image, and obsessive-compulsive symptoms with face to face interviews. The associations between the status of participants and the data were analyzed with NW group as a reference. OW status was associated with overeating and with frequent eating. UW status was associated with less frequent overeating and with longer sleep duration. AN status was associated with less frequent consumption of alcohol. BN status was associated with a larger discrepancy between the ideal and current body shape. Both OW status and BN were associated with more obsessive-compulsive symptoms. The results suggested that certain dietary, health, and psychological factors are associated with extreme weight conditions and EDs.     

Variations in the preproghrelin gene correlate with higher body mass index, fat mass, and body dissatisfaction in young Japanese women

BACKGROUND: Ghrelin is an endogenous peptide that stimulates growth hormone secretion, enhances appetite, and increases body weight and may play a role in eating disorders. OBJECTIVE: The purpose was to determine whether any preproghrelin gene variants are associated with anthropometric measures, circulating ghrelin, lipid concentrations, insulin resistance, or psychological measures relevant to eating disorders in young women. DESIGN: This cross-sectional study compared outcome measures between preproghrelin genotypes. The participants in the study included 264 Japanese women [university students with a mean (+/-SD) age of 20.4 +/- 0.7] with no history of eating disorders. The main outcomes were responses to the Eating Disorder Inventory-2 (EDI-2), anthropometric measures, measures of depression and anxiety, and fasting blood concentrations of acylated or desacyl ghrelin, lipids, glucose, and insulin. RESULTS: Two single nucleotide polymorphisms (SNPs) whose minor allele frequencies were >0.05--the Leu72Met (408 C-->A) SNP in exon 2 and the 3056 T-->C SNP in intron 2--were used for association analysis. The 3056C allele was significantly associated with a higher acylated ghrelin concentration (P=0.0021), body weight (P=0.011), body mass index (P=0.007), fat mass (P=0.012), waist circumference (P=0.008), and skinfold thickness (P=0.011) and a lower HDL-cholesterol concentration (P=0.02). Interestingly, the 3056C allele was related to elevated scores in the Drive for Thinness-Body Dissatisfaction (DT-BD) subscale of the EDI-2 (P=0.003). CONCLUSION: Our findings suggest that the preproghrelin gene 3056T-->C SNP is associated with changes in basal ghrelin concentrations and physical and psychological variables related to eating disorders and obesity.     

Emerging role of autoantibodies against appetite-regulating neuropeptides in eating disorders

OBJECTIVE: Recent findings of autoantibodies directed against melanocortin peptides suggest that these autoantibodies may represent a source of variability in peptidergic signaling that can be responsible for altered appetite and emotion in eating disorders. However, it is still unknown if autoantibodies directed against some other appetite-regulating neuropeptides and peptide hormones exist in healthy human subjects and if these autoantibodies can regulate appetite and emotion. METHODS: We determined the presence of autoantibodies against some key appetite-regulating neuropeptides and peptide hormones in sera of human subjects and in rats, and used animal models to study the role of alpha-melanocyte-stimulating hormone autoantibodies in food intake and anxiety. RESULTS: Immunoglobulin G and A autoantibodies against alpha-melanocyte-stimulating hormone, neuropeptide Y, agouti-related protein, ghrelin, leptin, and some other neuropeptides or peptide hormones involved in appetite control were present in healthy humans and rats. Animal models including active and passive transfer showed that alpha-melanocyte-stimulating hormone autoantibodies are involved in the regulation of feeding and anxiety. Sequence homology was found between neuropeptides and proteins from some members of intestinal microflora, whereas germ-free rats showed altered levels of autoantibodies directed against several neuropeptides. CONCLUSION: Autoantibodies directed against appetite-regulating neuropeptides and peptide hormones are emerging as important participants in the peptidergic mechanisms controlling motivated behavior. Furthermore, these autoantibodies could provide a link in the gut-brain axis and may represent new biological targets for the diagnosis and treatment of eating disorders.