Eating disorders and obesity are serious health problems with poor treatment outcomes and high relapse rates despite well-established treatments. Several studies have suggested that virtual reality technology could enhance the current treatment outcomes and could be used as an adjunctive tool in their treatment. This study aims to investigate the differences between eating virtual and real-life meals and test the hypothesis that eating a virtual meal can reduce hunger among healthy women. The study included 20 healthy women and used a randomized crossover design. The participants were asked to eat 1 introduction meal, 2 real meals, and 2 virtual meals, all containing real or virtual meatballs and potatoes. The real meals were eaten on a plate that had been placed on a scale that communicated with analytical software on a computer. The virtual meals were eaten in a room where participants were seated on a real chair in front of a real table and fitted with the virtual reality equipment. The eating behavior for both the real and virtual meals was filmed. Hunger was measured before and after the meals using questionnaires. There was a significant difference in hunger from baseline to after the real meal (mean difference=61.8, P<.001) but no significant change in hunger from before to after the virtual meal (mean difference=6.9, P=.10). There was no significant difference in food intake between the virtual and real meals (mean difference=36.8, P=.07). Meal duration was significantly shorter in the virtual meal (mean difference=–5.4, P<.001), which led to a higher eating rate (mean difference=82.9, P<.001). Some participants took bites and chewed during the virtual meal, but the number of bites and chews was lower than in the real meal. The meal duration was reduced from the first virtual meal to the second virtual meal, but no significant difference was observed between the 2 real meals. Eating a virtual meal does not appear to significantly reduce hunger in healthy individuals. Also, this methodology does not significantly result in eating behaviors identical to real-life conditions but does evoke chewing and bite behavior in certain individuals. ClinicalTrials.gov NCT05734209, https://clinicaltrials.gov/ct2/show/NCT05734209

Introduction Porter and Olmsted Teisberg suggested that the value of healthcare should be measured by treatment outcomes related to costs. Policy should financially reward treatment effects and in an outline of value-based healthcare, they predicted:1. State control policy yields variable effects, increasing costs2. Low price policy decreases effects, increasing costs3. Research and Development (R&D) policy increases effects, decreasing costsMethods The treatment of eating disorders in Region Stockholm, Sweden, in years 2012-2016 makes it possible to test these predictions because a State control, a Low price, and an R&D provider were contracted and the effects and costs of their treatments are publically available from Region Stockholm.Results The State control provider was contracted to provide more care services than the other providers. The average yearly number of patients treated to remission/patients treated was 164/714 (23%) at the State control provider, 41/170 (24) at the Low price provider, and 152/192 (79%) at the R&D provider. The average yearly budget was 73 million Swedish crowns (MSEK) compared to 49 MSEK at the R&D provider and 32 MSEK at the Low price provider (on average 30% lower per care service than the two other providers). The average cost to treat a patient to remission/patients treated was highest at the Low price provider (859 KSEK), followed by the State control provider (464 KSEK) and the R&D provider (327 KSEK).Conclusions The results confirm Porter and Olmsted Teisberg’s three predictions and suggest that an R&D policy increases the value of healthcare.### Competing Interest StatementComplete openness concerning financial arrangements is intended here. Brodin declares that he has no financial interests associated with this manuscript. Our research is carried out at the Karolinska Institute, where Sodersten is an emeritus professor. The research is translated clinically by Mando Group AB, a company started by Sodersten and Bergh, who have 47.5% of the stock each. Professor Michael Leon of the University of California at Irvine has 5%. Mando Group AB contracts with Region Stockholm every 4-6 years to treat patients with eating disorders. Mando Groups AB signed its first contract in 1997 with Region Stockholm and, since then, its treatment is one of the standards of care treatments offered to the citizens of Stockholm. This arrangement is the same as when Region Stockholm contracts with its own clinics to treat patients with all kinds of disease, including eating disorders. That is to say, Region Stockholm provides eating disorder services to the citizens of Stockholm both through a clinic of its own and through Mando Group AB. Until recently, there was a third provider of care for patients with eating disorders in Stockholm, which was a private clinic. Mando Group AB is the biggest provider of eating disorders services in Sweden as of 2019. All healthcare in Sweden is funded through the tax system; private pay is extremely uncommon. It should be added firstly, that Mando Group AB is in compliance with the recommendation of the International Committee of Medical Journal Editors on Author Responsibilities-Conflicts of Interest http://www.icmje.org/recommendations/browse/roles-and-responsibilities/author-responsibilities--conflicts-of-interest.html. Secondly, it should also be added that all profit that Mando Group AB has made has been re-invested in research and development and that there have been no dividends to stock owners. All of the above is declared in all manuscript submissions and thus far, journals have judged it necessary to publish only some of the details. It seems, however, that the potential ethical problem when scientists translate their research findings into the clinic in a company is not unlike that which arises when any scientist, in an academic setting is developing a theory and needs further economic funding for her/his work and may receive recognition and financial benefits for the work. The incentive is, in part, economic in this case as well and the ethical problem is similar in both cases. However, the more important incentive is the improvement of the treatment of patients with eating disorders. We are researchers working in an academic setting and like many other medical research institutes today, the Karolinska Institute encourages scientists to translate their research into the clinic in companies that aim to generate financial profits to be used for research and development (see: Strategy 2030 creating Karolinska Institutet's future together | Medarbetare (ki.se)### Funding StatementMando Group AB supports the work. Please consult the competing interests statement for details.### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:It was not considered necessary to obtain ethical permission because all data are publically available from Region Stockholm at: https://www.regionstockholm.se/om-regionstockholm/Information-in-English1I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesAll data produced in the present work are contained in the manuscript

Eating disorders (anorexia nervosa, bulimia nervosa, binge-eating disorder, and other specified eating or feeding disorders) have a combined prevalence of 13% and are associated with severe physical and psychosocial problems. Early diagnosis, which is important for effective treatment and prevention of undesirable long-term health consequences, imposes problems among non-specialist clinicians unfamiliar with these patients, such as those working in primary care. Early, accurate diagnosis, particularly in primary care, allows expert interventions early enough in the disorder to facilitate positive treatment outcomes. Computer-assisted diagnostic procedures offer a possible solution to this problem by providing expertise via an algorithm that has been developed from a large number of cases that have been diagnosed in person by expert diagnosticians and expert caregivers. A web-based system for determining an accurate diagnosis for patients suspected to suffer from an eating disorder was developed based on these data. The process is automated using an algorithm that estimates the respondent's probability of having an eating disorder and the type of eating disorder the individual has. The system provides a report that works as an aid for clinicians during the diagnostic process and serves as an educational tool for new clinicians.

Background Individuals with Anorexia Nervosa are often described as restless, hyperactive and having disturbed sleep. The result reproducibility and generalisability of these results are low due to the use of unreliable methods, different measurement methods and outcome measures. A reliable method to measure both physical activity and sleep is through accelerometry. The main purpose of the study was to quantify the physical activity and sleeping behaviour of anorexia nervosa patients. Another purpose was to increase result reproducibility and generalisability of the study. Material and methods Accelerometer data were collected from the first week of treatment of anorexia nervosa at an inpatient ward. Raw data from the Axivity AX3© accelerometer was used with the open-source package GGIR for analysis, in the free statistical software R. Accelerometer measurements were transformed into euclidean norm minus one with negative values rounded to zero (ENMO). Physical activity measurements of interest were 24h average ENMO, daytime average ENMO, inactivity, light activity, moderate activity, and vigorous activity. Sleep parameters of interest were sleep duration, sleep efficiency, awakenings, and wake after sleep onset. The sleep duration of different age groups was compared to recommendations by the National Sleep Foundation using a Fisher’s exact test. Results Of 67 patients, due to data quality 58 (93% female) were included in the analysis. Average age of participants was 17.8 (±6.9) years and body mass index was 15.5 (±1.9) kg/m2. Daytime average ENMO was 17.4 (±5.1) mg. Participants spent 862.6 (±66.2) min per day inactive, 88.4 (±22.6) min with light activities, 25.8 (±16.7) min with moderate activities and 0.5 (±1.8) min with vigorous activities. Participants slept for 461.0 (±68.4) min, waking up 1.45 (±1.25) times per night for 54.6 (±35.8) min, having an average sleep quality of 0.88 (±0.10). 31% of participants met sleep recommendations, with a significantly higher number of 6–13 year old patients failing to reach recommendations compared to 14–25 year old patients. Conclusion The patient group spent most of their time inactive at the beginning of treatment. Most patients failed to reach sleep recommendations. The use of raw data and opensource software should ensure result reproducibility, enable comparison across points in treatment and comparison with healthy individuals.

Background: Anorexia nervosa is one of the more severe eating disorders, which is characterized by reduced food intake, leading to emaciation and psychological maladjustment. Treatment outcomes are often discouraging, with most interventions displaying a recovery rate below 50%, a dropout rate from 20% to 50%, and a high risk of relapse. Patients with anorexia nervosa often display anxiety and aversive behaviors toward food. Virtual reality has been successful in treating vertigo, anxiety disorder, and posttraumatic stress syndrome, and could potentially be used as an aid in treating eating disorders. Objective: The aim of this study was to evaluate the feasibility and usability of an immersive virtual reality technology administered through an app for use by patients with eating disorders. Methods: Twenty-six participants, including 19 eating disorder clinic personnel and 5 information technology personnel, were recruited through emails and personal invitations. Participants handled virtual food and utensils on an app using immersive virtual reality technology comprising a headset and two hand controllers. In the app, the participants learned about the available actions through a tutorial and they were introduced to a food challenge. The challenge consisted of a meal type (meatballs, potatoes, sauce, and lingonberries) that is typically difficult for patients with anorexia nervosa to eat in real life. Participants were instructed, via visual feedback from the app, to eat at a healthy rate, which is also a challenge for patients. Participants rated the feasibility and usability of the app by responding to the mHealth Evidence Reporting and Assessment checklist, the 10-item System Usability Scale, and the 20-point heuristic evaluation questionnaire. A cognitive walkthrough was performed using video recordings of participant interactions in the virtual environment. Results: The mean age of participants was 37.9 (SD 9.7) years. Half of the participants had previous experience with virtual reality. Answers to the mHealth Evidence Reporting and Assessment checklist suggested that implementation of the app would face minor infrastructural, technological, interoperability, financial, and adoption problems. There was some disagreement on intervention delivery, specifically regarding frequency of use; however, most of the participants agreed that the app should be used at least once per week. The app received a mean score of 73.4 (range 55-90), earning an overall "good" rating. The mean score of single items of the heuristic evaluation questionnaire was 3.6 out of 5. The lowest score (2.6) was given to the "accuracy" item. During the cognitive walkthrough, 32% of the participants displayed difficulty in understanding what to do at the initial selection screen. However, after passing the selection screen, all participants understood how to progress through the tasks. Conclusions: Participants found the app to be usable and eating disorder personnel were positive regarding its fit with current treatment methods. Along with the food item challenges in the current app, participants considered that the app requires improvement to offer environmental and social (eg, crowded room vs eating alone) challenges.

Masculinization and feminization of rat sexual behavior has been supposed to occur during a short postnatal period. However, much data have made it evident that these processes may continue until adolescence. In the present study, we evaluated whether androgen treatment of females from postnatal day 20 and onwards could alter sexual motivation and behavior in a male direction. Juveniles were ovariectomized on day 20 and concurrently implanted with Silastic capsules containing either testosterone or dihydrotestosterone. Controls were implanted with an empty capsule. Tests for sexual incentive motivation and male sexual behavior were performed every fifth day when the females were between 50 and 75 days of age. At day 80, a test for female sexual behavior was performed. Females treated with testosterone approached a female sexual incentive far more than a male incentive, showing that sexual motivation had been changed in a male-like direction. Dihydrotestosterone had a similar, albeit smaller, effect. Females implanted with an empty capsule approached both incentives equally. Testosterone produced a high level of mounting behavior, whereas intromission-like behavioral patterns were rare and ejaculation-like behavior was absent. In the test for female sexual behavior, the testosterone-treated animals displayed a relatively high lordosis quotient, far above that displayed in females implanted with dihydrotestosterone or an empty capsule. It is concluded that treatment with an aromatizable androgen during the peripubertal-adolescent period masculinizes sexual motivation and partly sexual behavior. A non-aromatizable androgen weakly masculinize sexual motivation without enhancing male sexual behavior. It appears that simultaneous actions on androgen and estrogen receptors are needed for significant masculinization during the period studied here. Since the testosterone-treated females displayed lordosis, sexual behavior was not defeminized. In sum, these results suggest that sexual differentiation continues well into the peripubertal and adolescent periods.

This paper reviews the files in the archive of the Nobel Prize Committee for Physiology or Medicine on the Austrian physiologist and pioneering researcher in the emerging fields of urology and sexual medicine: Eugen Steinach (1861-1944). It reconstructs and analyzes why and by whom Steinach was nominated for the Nobel Prize between 1920 and 1938 and discusses the reasons why he never received the award, although the Nobel Committee judged him as prizeworthy. Steinach's Nobel nominee career is extraordinary - not only because of his strong support by renowned international nominators from different scientific and medical disciplines, but also because of the controversial discussions within the Nobel Committee on his achievements, colored by the debates in the international scientific community. The Nobel Prize story adds a new perspective on how contemporary international scholars evaluated Steinach's research on reproduction, "male-making" females, "female-making" males, homosexuality, and the concept of rejuvenation.

Objective To report the outcomes of eating disorders treatment in Sweden in 2012-2016. Design The number of patients treated and the number of patients not fulfilling an eating disorders diagnosis (remission) at 1 year of follow-up at the clinics listed in the National Quality Registry for Eating Disorders Treatment were analysed. The published outcomes at three clinics, which used survival analysis to estimate outcomes, were compared with their outcomes in the registry. Outcomes at the three biggest clinics were compared. Setting All eating disorders clinics. Participants All patients treated at eating disorders clinics. Intervention Cognitive-behavioural therapy at most clinics and normalisation of eating behaviour at the three clinics with published outcomes. Outcome measure Proportion of patients in remission. Results About 2600 patients were treated annually, fewer than half were followed up and remission rates decreased from 21% in 2014 to 14% in 2016. Outcomes, which differed among clinics and within clinics over time, have been publicly overestimated by excluding patients lost to follow-up. The published estimated rate of remission at three clinics that treated 1200 patients in 1993-2011 was 27%, 28% and 40% at 1 year of follow-up. The average rate of remission over the three last years at the biggest of these clinics was 36% but decreased from 29% and 30% to 16 and 14% at the two other of the biggest clinics. Conclusions With more than half the patients lost to follow-up and no data on relapse in the National Quality Registry, it is difficult to estimate the effects of eating disorders treatment in Sweden. Analysis of time to clinically significant events, including an extended period of follow-up, has improved the quality of the estimates at three clinics. Overestimation of remission rates has misled healthcare policies. The effect of eating disorders treatment has also been overestimated internationally.

On the standard perspective, anorexia nervosa and other eating disorders are caused by genetically determined, neurochemically mediated mental illnesses. Standard treatment, cognitive behavioral therapy (CBT), targets cognitive processes thought to maintain the disorders. Effective neurochemically based treatments are not available and the rate of remission is ≤25% 1 year after CBT, with unknown outcomes in the long-term. With starvation as the major threat in biological history, the evolutionary perspective focuses on foraging for food and eating behavior. A neural network, including hypothalamic arcuate peptide-neurons, brainstem serotonin- and dopamine-neurons and their prefrontal cortical projections, mediates (rather than controls) the behavioral adaptations to variations in food availability; activation of the network is associated with opposing behavioral outcomes depending upon external variations. In the clinic, the control of eating behavior is therefore outsourced to a machine that provides feedback on how to eat. Hundreds of eating disorders patients have recovered by practicing eating; the rate of remission is 75% in on average 1 year of treatment, the rate of relapse is 10% over 5 years of follow-up and no patient has died. A two-parameter asymptotic exponential growth curve modeled the eating behavior of 17 healthy women but not that of 17 women with anorexia nervosa. When in remission, the eating behavior of the anorexic women approached that of the healthy women. It is suggested that the treatment of eating disorders should focus on eating behavior.

Mental causation takes explanatory priority over evolutionary biology in most accounts of eating disorders. The evolutionary threat of starvation has produced a brain that assists us in the search for food and mental change emerges as a consequence. The major mental causation hypothesis: anxiety causes eating disorders, has been extensively tested and falsified. The subsidiary hypothesis: anxiety and eating disorders are caused by the same genotype, generates inconsistent results because the phenotypes are not traits, but vary along dimensions. Challenging the mental causation hypothesis in Feighner et al. (1972) noted that anorexic patients are physically hyperactive, hoarding for food, and they are rewarded for maintaining a low body weight. In 1996, Feighner's hypothesis was formalized, relating the patients' behavioral phenotype to the brain mechanisms of reward and attention (Bergh and Södersten, 1996), and in 2002, the hypothesis was clinically verified by training patients how to eat normally, thus improving outcomes (Bergh et al., 2002). Seventeen years later we provide evidence supporting Feighner's hypothesis by demonstrating that in 2012, 20 out of 37 patients who were referred by a psychiatrist, had a psychiatric diagnosis that differed from the diagnosis indicated by the SCID-I. Out of the 174 patients who were admitted in 2012, most through self-referral, there was significant disagreement between the outcomes of the SCID-I interview and the patient's subjective experience of a psychiatric problem in 110 of the cases. In addition, 358 anorexic patients treated to remission scored high on the Comprehensive Psychopathological Rating Scale, but an item response analysis indicated one (unknown) underlying dimension, rather than the three dimensions the scale can dissociate in patients with psychiatric disorders. These results indicate that psychiatric diagnoses, which are reliable and valid in patients with psychiatric disorders, are less well suited for patients with anorexia. The results are in accord with the hypothesis of the present Research Topic, that eating disorders are not always caused by disturbed psychological processes, and support the alternative, clinically relevant hypothesis that the behavioral phenotype of the patients should be addressed directly.

The structure of the cumulative food intake (CFI) curve has been associated with obesity and eating disorders. Scales that record the weight loss of a plate from which a subject eats food are used for capturing this curve; however, their measurements are contaminated by additive noise and are distorted by certain types of artifacts. This paper presents an algorithm for automatically processing continuous in-meal weight measurements in order to extract the clean CFI curve and in-meal eating indicators, such as total food intake and food intake rate. The algorithm relies on the representation of the weight-time series by a string of symbols that correspond to events such as bites or food additions. A context-free grammar is next used to model a meal as a sequence of such events. The selection of the most likely parse tree is finally used to determine the predicted eating sequence. The algorithm is evaluated on a dataset of 113 meals collected using the Mandometer, a scale that continuously samples plate weight during eating. We evaluate the effectiveness for seven indicators and for bite-instance detection. We compare our approach with three state-of-the-art algorithms, and achieve the lowest error rates for most indicators (24 g for total meal weight). The proposed algorithm extracts the parameters of the CFI curve automatically, eliminating the need for manual data processing, and thus facilitating large-scale studies of eating behavior.

Subjects eat food from a plate that sits on a scale connected to a computer that records the weight loss of the plate during the meal and makes up a curve of food intake, meal duration and rate of eating modeled by a quadratic equation. The purpose of the method is to change eating behavior by providing visual feedback on the computer screen that the subject can adapt to because her/his own rate of eating appears on the screen during the meal. The data generated by the method is automatically analyzed and fitted to the quadratic equation using a custom made algorithm. The method has the advantage of recording eating behavior objectively and offers the possibility of changing eating behavior both in experiments and in clinical practice. A limitation may be that experimental subjects are affected by the method. The same limitation may be an advantage in clinical practice, as eating behavior is more easily stabilized by the method. A treatment that uses this method has normalized body weight and restored the health of several hundred patients with anorexia nervosa and other eating disorders and has reduced the weight and improved the health of severely overweight patients.

Acta Psychiatrica ScandinavicaVolume 135, Issue 3 p. 266-267 Letter to the Editor Anxiolytic effect of warmth in anorexia nervosa M. Zandian, M. Zandian Karolinska Institutet, Section of Applied Neuroendocrinology, Mandometer Clinic, Huddinge, SwedenSearch for more papers by this authorE. Holmstedt, E. Holmstedt Karolinska Institutet, Section of Applied Neuroendocrinology, Mandometer Clinic, Huddinge, SwedenSearch for more papers by this authorA. Larsson, A. Larsson Karolinska Institutet, Section of Applied Neuroendocrinology, Mandometer Clinic, Huddinge, SwedenSearch for more papers by this authorC. Bergh, C. Bergh Karolinska Institutet, Section of Applied Neuroendocrinology, Mandometer Clinic, Huddinge, SwedenSearch for more papers by this authorU. Brodin, U. Brodin Karolinska Institutet, Section of Applied Neuroendocrinology, Mandometer Clinic, Huddinge, SwedenSearch for more papers by this authorP. Södersten, P. Södersten per.sodersten@ki.se Karolinska Institutet, Section of Applied Neuroendocrinology, Mandometer Clinic, Huddinge, SwedenSearch for more papers by this author M. Zandian, M. Zandian Karolinska Institutet, Section of Applied Neuroendocrinology, Mandometer Clinic, Huddinge, SwedenSearch for more papers by this authorE. Holmstedt, E. Holmstedt Karolinska Institutet, Section of Applied Neuroendocrinology, Mandometer Clinic, Huddinge, SwedenSearch for more papers by this authorA. Larsson, A. Larsson Karolinska Institutet, Section of Applied Neuroendocrinology, Mandometer Clinic, Huddinge, SwedenSearch for more papers by this authorC. Bergh, C. Bergh Karolinska Institutet, Section of Applied Neuroendocrinology, Mandometer Clinic, Huddinge, SwedenSearch for more papers by this authorU. Brodin, U. Brodin Karolinska Institutet, Section of Applied Neuroendocrinology, Mandometer Clinic, Huddinge, SwedenSearch for more papers by this authorP. Södersten, P. Södersten per.sodersten@ki.se Karolinska Institutet, Section of Applied Neuroendocrinology, Mandometer Clinic, Huddinge, SwedenSearch for more papers by this author First published: 02 January 2017 https://doi.org/10.1111/acps.12691Citations: 13Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume135, Issue3March 2017Pages 266-267 RelatedInformation

We examine the science and evidence supporting cognitive behavior therapy (CBT) for the treatment of bulimia nervosa and other eating disorders. Recent trials focusing on the abnormal cognitive and emotional aspects of bulimia have reported a remission rate of about 45%, and a relapse rate of about 30% within one year. However, an early CBT trial that emphasized the normalization of eating behavior had a better outcome than treatment that focused on cognitive intervention. In support of this finding, another treatment, that restores a normal eating behavior using mealtime feedback, has an estimated remission rate of about 75% and a relapse rate of about 10% over five years. Moreover, when eating behavior was normalized, cognitive and emotional abnormalities were resolved at remission without cognitive therapy. The critical aspect of the CBT treatment of bulimia nervosa therefore may actually have been the normalization of eating behavior. (C) 2017 The Authors. Published by Elsevier Inc

We have suggested that reduced food intake increases the risk for anorexia nervosa by engaging mesolimbic dopamine neurons, thereby initially rewarding dieting. Recent fMRI studies have confirmed that dopamine neurons are activated in anorexia nervosa, but it is not clear whether this response is due to the disorder or to its resulting nutritional deficit. When the body senses the shortage of nutrients, it rapidly shifts behavior toward foraging for food as a normal physiological response and the mesolimbic dopamine neurons may be involved in that process. On the other hand, the altered dopamine status of anorexics has been suggested to result from a brain abnormality that underlies their complex emotional disorder. We suggest that the outcomes of the treatments that emerge from that perspective remain poor because they target the mental symptoms that are actually the consequences of the food deprivation that accompanies anorexia. On the other hand, a method that normalizes the disordered eating behavior of anorexics results in much better physiological, behavioral, and emotional outcomes. (C) 2015 Elsevier Ltd. All rights reserved.

GENERAL COMMENTARY article Front. Neurosci., 25 October 2016Sec. Neuroendocrine Science Volume 10 - 2016 | https://doi.org/10.3389/fnins.2016.00483

Christopher Ochner and colleagues address the very important issue of whether reversal of the neurohormonal adaptations associated with obesity is physiologically possible. They suggest that these changes are irreversible and thus prevent the possibility of designing successful strategies using lifestyle interventions. They argue that any treatment of obesity should include direct biological intervention.1Ochner CN Tsai AG Kushner RF Wadden TA Treating obesity seriously: when recommendations for lifestyle change confront biological adaptations.Lancet Diabetes Endocrinol. 2015; 3: 232-234Summary Full Text Full Text PDF Scopus (74) Google Scholar For example, weight loss induced by a 10-week low-calorie diet in obese patients has been reported to cause an increase in the concentration of ghrelin, a potent hunger hormone. Remarkably, this hormonal change, and other changes thought to increase hunger and decrease satiety, persist at 1 year after the intervention, providing an explanation for why diet-induced weight loss is so difficult to maintain.2Sumithran P Prendergast LA Delbridge E et al.Long-term persistence of hormonal adaptations to weight loss.N Engl J Med. 2011; 365: 1597-1604Crossref PubMed Scopus (902) Google Scholar We believe this argument is rather simplistic, and although we have replicated the long-term increase in the concentration of ghrelin after diet-induced weight loss in obese adolescents, this effect was reversed in patients who practiced eating less food at a reduced speed by use of real-time feedback on a computer screen that told them how much food and how rapidly they should be eating (figure).3Galhardo J Hunt LP Lightman SL et al.Normalizing eating behavior reduces body weight and improves gastrointestinal hormonal secretion in obese adolescents.J Clin Endocrinol Metab. 2012; 97: E193-E201Crossref PubMed Scopus (59) Google Scholar Control of eating behaviour in this way also normalised some of the other neuroendocrine changes associated with obesity and was more effective at reducing bodyweight and improving health than was a standard diet intervention. These improvements persisted for 6 months after the intervention.4Ford AL Bergh C Södersten P et al.Treatment of childhood obesity by retraining eating behaviour: randomised controlled trial.BMJ. 2010; 340: b5388Crossref Scopus (141) Google Scholar The speed of eating increases in obesity,5Robinson E Almiron-Roig E Rutters F et al.A systematic review and meta-analysis examining the effect of eating rate on energy intake and hunger.Am J Clin Nutr. 2014; 100: 123-151Crossref PubMed Scopus (204) Google Scholar and by targeting this behavioural change gastrointestinal hormonal responses can be normalised. Ochner and colleagues noted that gastric bypass surgery also reverses the hormonal abnormalities of obesity.1Ochner CN Tsai AG Kushner RF Wadden TA Treating obesity seriously: when recommendations for lifestyle change confront biological adaptations.Lancet Diabetes Endocrinol. 2015; 3: 232-234Summary Full Text Full Text PDF Scopus (74) Google Scholar The reduction in fasting ghrelin concentrations achieved by behavioural intervention is similar to that obtained by gastric bypass. Addressing eating behaviours, such as eating speed, directly through targeted behavioural modification might be a useful avenue to explore before resorting to surgery. PS and CB own stock in Mando Group AB, the company that treats underweight and overweight patients using the Mandometer. PS and CB own the intellectual property rights to Mandometer (a patented device). JS and SL declare no competing interests. We thank Björn Meister for his advice. Treating obesity seriously: when recommendations for lifestyle change confront biological adaptationsMany clinicians are not adequately aware of the reasons that individuals with obesity struggle to achieve and maintain weight loss,1 and this poor awareness precludes the provision of effective intervention.2 Irrespective of starting weight, caloric restriction triggers several biological adaptations designed to prevent starvation.3 These adaptations might be potent enough to undermine the long-term effectiveness of lifestyle modification in most individuals with obesity, particularly in an environment that promotes energy overconsumption. Full-Text PDF Reversible biological adaptations in obesity – Authors' replyWe thank Per Södersten and colleagues for their thoughtful commentary, and appreciate the contribution of their research.1 However, its description primarily argues against contentions that were not made in our Comment,2 which necessitates some clarification. We state that the neurohormonal adaptations to sustained obesity often persist indefinitely, but we do not suggest that is it not physiologically possible to reverse them. Further, the increased ghrelin following low-calorie diet described by Södersten and colleagues is an example of an adaptation to caloric restriction, which differs from biological adaptations to sustained obesity that serve to maintain or even increase an individual's adipose storage capacity. Full-Text PDF

In the 1930s, Eugen Steinach's group found that estradiol induces lordosis in castrated rats and reduces the threshold dose of testosterone that is necessary for the induction of ejaculation, and that estradiol-treated intact rats display lordosis as well as mounting and ejaculation. The bisexual, estrogen-sensitive male had been demonstrated. Another major, albeit contrasting, discovery was made in the 1950s, when William Young's group reported that male guinea pigs and prenatally testosterone-treated female guinea pigs are relatively insensitive to estrogen when tested for lordosis as adults. Reduced estrogen sensitivity was part of the new concept of organization of the neural tissues mediating the sexual behavior of females into tissues similar to those of males. The importance of neural organization by early androgen stimulation was realized immediately and led to the discovery of a variety of sex differences in the brains of adult animals. By contrast, the importance of the metabolism of testosterone into estrogen in the male was recognized only after a delay. While the finding that males are sensitive to estrogen was based on Bernhard Zondek's discovery in 1934 that testosterone is metabolized into estrogen in males, the finding that males are insensitive to estrogen was based on the hypothesis that testosterone-male sexual behavior is the typical relationship in the male. It is suggested that this difference in theoretical framework explains the discrepancies in some of the reported results.