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Anorexia nervosa: directions for future research. Study Group on Anorexia Nervosa.

On September 27-29, 1993, the Study Group on Anorexia Nervosa (AN): Basic Mechanisms, Clinical Approaches and Treatment met in Geneva, Switzerland to discuss recent progress in research on anorexia nervosa, and to identify directions for future studies. Anorexia nervosa is a disorder of unknown etiology, without a specific curative treatment, affecting mostly individuals in adolescence and early adulthood, with significant morbidity and mortality, and having a major impact on psychosocial and vocational development. In anorexia nervosa there are severe disturbances in virtually every endocrine system, such as the hypothalamic-pituitary-adrenal (HPA) axis, the hypothalamic-pituitary-gonadal (HPG) axis, the hypothalamic-pituitary-thyroid (HPT) axis, the growth hormone (GH)/somatomedin C (IGF-1) system, and the central and peripheral arginine vasopressin (AVP) systems. Furthermore, classical neurotransmitter systems, such as the cholinergic noradrenergic, and serotonergic systems, are abnormally regulated in anorexia nervosa. New research data is also emerging on the abnormal regulation of immune function in this disorder. The Study Group concluded that even though several biological systems are abnormally regulated in anorexia nervosa, there is no biological test which is specific enough to make the diagnosis of the disorder. New directions for research in anorexia nervosa are identified and discussed in this report. Finally, the Study Group proposed future meetings to bring together clinical and pre-clinical (pharmacological, biochemical, and molecular) scientists studying topics, such as neuroendocrine function, which are important in the biology of anorexia nervosa.

Anorexia Nervosa↗

Diminished amphetamine anorexia and enhanced fenfluramine anorexia after midbrain 6-hydroxydopamine.

Rats were made hyperphagic by 6-hydroxydopamine (6-OHDA) injected bilaterally into the ventral midbrain; then they were restricted to a 6 h/day feeding schedule and tested for appetite suppression with amphetamine and fenfluramine in randomized order. Amphetamine anorexia was diminished while fenfluramine anorexia was enhanced (both P less than 0.001). The opposite effect on fenfluramine anorexia shows that the effect of 6-OHDA on amphetamine anorexia was not due to hyperphagia masking the anorexia. Norepinephrine in the forebrain was 90% depleted, but DA and serotonin levels were within 9% of normal. These results demonstrate a new way to dissociate amphetamine and fenfluramine anorexia, as others have done with lateral hypothalamic lesions or DA depletion. The 6-OHDA injections, which were of a type that cause hyperphagia, apparently destroyed a substrate for amphetamine anorexia and also facilitated a substrate for fenfluramine anorexia.

Animals↗

Insulin reverses ammonia-induced anorexia and experimental cancer anorexia.

Previous experiments suggest that experimental cancer-induced anorexia is associated with hyperammonemia and that daily injections of insulin may attenuate the anorexia for several days. In the present study, we determined whether similar daily insulin treatments would correct anorexia induced by the infusion of ammonium salts and compared this feeding response with that of insulin-treated tumor-bearing (TB) rats. Daily treatment of control and anorectic TB rats with systemically administered insulin for six days increased feeding in all control rats and 40% of the TB rats. All insulin-treated groups exhibited equal degrees of hypoglycemia irrespective of anorexia. Basal concentrations of lactate and glucagon were elevated in saline-treated TB rats. Plasma lactate levels were normalized by insulin treatment, whereas glucagon was normalized only in the TB rats that fed to insulin and increased further in TB rats that did not feed to insulin. Elevated hypothalamic tyrosine was reduced in insulin-treated TB rats that ate, and 5-hydroxy-indoleacetic acid was increased further when the rats did not eat. Insulin also blocked anorexia resulting from the intravenous infusion of ammonium salts. Hypothalamic concentrations of tyrosine and tryptophan were increased by the ammonia infusion and reduced significantly in insulin-treated infused rats. These results indicate that insulin treatment can reverse experimental cancer-induced anorexia and hyperammonemia-induced anorexia. Neurochemical changes associated with these treatments are also similar, but not identical.

Ammonia↗

Bone size and volumetric density in women with anorexia nervosa receiving estrogen replacement therapy and in women recovered from anorexia nervosa.

Anorexia nervosa is associated with bone loss during adulthood, but may also delay skeletal growth and mineral accrual during growth. We asked the following questions. 1) Is anorexia nervosa associated with reduced bone size and reduced volumetric bone mineral density (vBMD)? 2) Is estrogen replacement therapy (ERT) or recovery from anorexia nervosa associated with normal bone size and vBMD? Using dual-energy x-ray absorptiometry, we measured bone size and vBMD of the third lumbar vertebra and femoral neck in a cross-sectional study of 161 female patients: 77 with untreated anorexia nervosa, 58 with anorexia nervosa receiving ERT, 26 recovered from anorexia nervosa, and 205 healthy age-matched controls. Results were expressed as the SD or z-score (mean +/- SEM). Deficits in vertebral body and femoral neck width in untreated women were -1.0 +/- 0.1 and -0.3 +/- 0.1 SD (P < 0.001 and P < 0.05, respectively). Deficits in bone width were less in the ERT-treated women than in untreated women at the vertebral body (-0.6 +/- 0.1 SD; P < 0.001), but not at the femoral neck (-0.4 +/- 0.2 SD; P < 0.05). There were no significant deficits in vertebral body and femoral neck width in recovered women (both -0.3 +/- 0.2 SD; P = NS). In untreated women, vertebral and femoral neck vBMD were -1.6 +/- 0.1 and -1.1 +/- 0.1 SD, respectively (both P < 0.001), less severely reduced in ERT-treated women (-1.2 +/- 0.2 and -0.6 +/- 0.2 SD, respectively; both P < 0.001), and least reduced in recovered women (-0.6 +/- 0.1 and -0.5 +/- 0.2 SD; P < 0.01 and P < 0.05, respectively). After adjusting for differences in fat and lean mass, vertebral body and femoral neck width were no longer reduced in untreated, ERT-treated, and recovered women. Adjustment for body composition had little effect on group difference in vBMD. Bone fragility in anorexia nervosa is due to reduced bone size and reduced vBMD. Although causality cannot be inferred in cross-sectional studies, the data are consistent with the view that malnutrition may contribute to reduced bone size, whereas estrogen deficiency may reduce vBMD. The use of ERT early in disease is a reasonable component of management if the chance of recovery appears remote.

Absorptiometry, Photon↗

Anorexia nervosa "restricters" who purge: implications for subtyping anorexia nervosa.

It has not been clear from earlier studies whether it is binge eating per se or the compensatory behaviors frequently associated with binge eating (i.e., self-induced vomiting and/or laxative abuse) that provide the most relevant marker for subclassifying anorexia nervosa. The current study addressed this question by comparing the clinical and psychological features of three groups of anorexia nervosa patients: "pure restricting" patients who do not binge (by definition) and who also do not purge (AN-R, N = 116); "restricting-purging" patients who engage in purging behavior (AN-RP, N = 74); and anorexia nervosa "bulimics" who binge eat as defined in earlier studies (AN-B, N = 190). While all three groups displayed similar levels of psychological disturbance on many variables, the overall pattern of findings indicates that the AN-RP group displays significantly more psychopathology than the AN-R group and their profile of disturbance is very similar to that observed with the AN-B group. Thus, anorexia nervosa patients who purge, regardless of whether or not they report objective binge episodes, may be meaningfully distinguished from nonpurging patients. These results, combined with the medical risks associated with purging behaviors and the formidable problems associated with the definition of binge eating, support a sub-typing system for anorexia nervosa based on the presence or absence of purging rather than binge eating.

Adult↗

Anorexia nervosa and "reverse anorexia" among 108 male bodybuilders.

Two disorders of body image encountered in a study of 108 bodybuilders are described. In a study of the psychiatric effects of anabolic steroids, structured interviews were administered to 55 bodybuilders who had used anabolic steroids and 53 non-user controls. Three (2.8%) of the subjects reported a history of anorexia nervosa--a rate far higher than the 0.02% rate typically reported among American men (P < .001). Nine (8.3%) of the subjects, two of whom were former anorexics, described a "reverse anorexia" syndrome, where they believed that they appeared small and weak even though they were actually large and muscular. Reverse anorexic subjects reported that they declined social invitations, refused to be seen at the beach, or wore heavy clothes even in the heat of summer because they feared that they looked too small. All nine reverse anorexia cases occurred among steroid users; none occurred among non-users (P < .003). Four subjects reported that their reverse anorexic symptoms contributed to their decision to start using steroids. Disorders of body image, including both anorexia nervosa and its reverse form, may occur frequently in men who lift weights regularly. Reverse anorexia may precipitate or perpetuate the use of anabolic steroids in some individuals.

Adult↗

Anorexia tardive--late onset marital anorexia nervosa.

Most cases of anorexia nervosa start in adolescence but a sizeable number can develop the condition at any late age. The term Anorexia Tardive is reintroduced to describe woman who develop anorexia nervosa at or after the time of their marriages. The paper reports the study of the background and personalities of 50 such women, together with their husbands in 45 cases, and the parts played by both in the condition. The women were divided into 4 groups; those who developed Anorexia Tardive (1) in the engaged period, (2) after marriage and before pregnancy, (3) after childbirth and (4) at or after the menopause. In the first three groups Anorexia Tardive developed as a maladaptive solution to a growing marital crisis. Many of the husbands were immature men who readily accepted a sick dependent wife. Group 4 women differed in a number of respects and their loss of weight ultimately came to express a desire to die. Outcome and prognosis are described.

Adult↗

Pro-anorexia, weight-loss drugs and the internet: an "anti-recovery" explanatory model of anorexia.

This paper explores the online "pro-anorexia" underground, a movement that supports those with anorexia and adopts an "anti-recovery" perspective on the disease. While encouraging a "healthy" diet to sustain an anorexic way-of-life, the movement also recommends the radical use of weight-loss pharmaceuticals to pursue and maintain low body weight, in contrast to their conventional use to treat obesity. Using ethnographic and interview data collected from participants in the "Anagrrl" website and online forum, we analyse the pro-anorexia (or "pro-ana") movement in terms of its underlying "explanatory model" of the disease, and contrast it with medical, psychosocial, sociocultural and feminist models that encourage a "normalisation" of body shape and weight. We suggest that for participants in pro-ana, anorexia represents stability and control, and Anagrrl offers support and guidance for those who wish to remain in this "sanctuary". We discuss the pro-anorexia movement's use of the internet to facilitate resistance to medical and social theories of disease, and its subversion of pharmaceutical technologies.

Adolescent↗

"Anorexia saved my life": coincidental anorexia nervosa and cerebral meningioma.

OBJECTIVE: We report on a 13-year-old girl with coincidental occult intracranial tumor and early-onset anorexia nervosa. METHOD: The cerebral meningioma was discovered fortuitously as the result of a research project using SPECT imaging to locate a neurobiological substrate in patients with anorexia nervosa. Without SPECT, the meningioma would have remained undiagnosed until it had become symptomatic. The two conditions appear to have been completely unrelated. RESULTS AND DISCUSSION: The case highlights two important points. First, intracranial pathology should also be considered however certain is the diagnosis of early-onset anorexia nervosa. Second, neuroimaging plays an important part in diagnosing early-onset anorexia nervosa, both from a clinical and a research prospective.

Adolescent↗

Is running an analogue of anorexia nervosa? An empirical study of obligatory running and anorexia nervosa.

A recent report suggested that compulsive runners share a common set of psychological traits and behavioral dispositions with patients with anorexia nervosa. In an effort to objectively assess the similarity between anorexia nervosa and obligatory running, 43 runners and 24 patients with anorexia nervosa completed the Minnesota Multiphasic Personality Inventory (MMPI). Results indicated that the obligatory runners generally scored within the normal range, while the anorectic patients did not. The anorectic patients obtained more pathological scores than the runners on eight of the ten clinical subscales of the MMPI. Fifty percent of the anorectic patients obtained elevations on three or more of the MMPI subscales, while no runners obtained more than two scale elevations. Depression (scale 2) and psychopathy (scale 4) were particularly prevalent in the anorectic group. We conclude that obligatory runners do not suffer from the same degree of psychopathology as do patients with anorexia nervosa.

Adult↗

Stress-induced anorexia: implications for anorexia nervosa.

Recent studies have suggested that stress may be a precipitating factor in the etiology of anorexia nervosa. The present paper examines the possible mechanisms involved in stress-induced anorexia and suggests how stress-induced changes in opiate systems, the hypothalamic-pituitary-adrenal axis and serotonergic systems may provide an explanation of many of the physiological and behavioral responses observed in anorexia nervosa. The present paper suggests that certain psychosocial and endocrinological factors may interact to provide the setting conditions for the syndrome. Finally, it is suggested that a dual therapeutic approach is required in that the syndrome needs to be treated both physiologically and psychologically to prevent relapse.

Adolescent↗

Involvement of corticotropin-releasing factor in restraint stress-induced anorexia and reversion of the anorexia by somatostatin in the rat.

The mechanism by which restraint stress induces suppression of food intake and the influence of intracerebroventricular (icv) administration of somatostatin on the anorexia induced by restraint stress were examined in the rat. Ninety minutes of restraint stress reduced food intake of rats to approximately 60% that of control. Anorexia induced by 90 min restraint stress was partially reversed by icv administration of alpha-helical CRF (9-41), a corticotropin-releasing factor (CRF) antagonist, and completely reversed by anti-CRF gamma-globulin. These results provide further evidence in support of the theory that CRF is involved in the inhibitory mechanism of food intake in restraint stress. ICV administration of somatostatin 14 and SMS 201-995, an analog of somatostatin, also reversed restraint stress-induced anorexia. It is, therefore, suggested that somatostatin may counteract the suppressive action of CRF on food intake in stress.

Animals↗

Cancer anorexia: a model for the understanding and treatment of secondary anorexia.

Under normal conditions, food intake is controlled in the hypothalamus by: (i) transducing metabolic/sensorial inputs arising from the periphery into neuronal response; (ii) integrating the information originating from different tissues; and (iii) triggering the appropriate feeding responses. Thus, the anorexia associated with a number of chronic diseases, including cancer, may result from an abnormal input of information to the hypothalamus, or in its defective transduction and integration, or in the induction of exaggerated and inappropriate feeding responses. Currently available data suggest that the pathogenesis of secondary anorexia is multifactorial, and involves most of the neuronal signalling pathways modulating energy intake, including hormones (e.g. leptin), neuropeptides (e.g. NPY), cytokines (e.g. IL-1, IL-6, TNF) and neurotransmitters (e.g. serotonin and dopamine). However, it is unlikely that they represent separate and distinct pathogenic mechanisms, rather it appears that close interrelationships may exist among them. In line with this reasoning, consistent experimental and human data suggest that the hypothalamic serotonergic neurotransmission may represent a major target on which different anorexia-related factors converge. Thus, interfering pharmacologically with hypothalamic serotonin synthesis and activity may represent an effective therapeutic strategy in anorectic patients, as suggested by recent preliminary clinical data.

Anorexia↗

Hypoleptinaemia in patients with anorexia nervosa and in elite gymnasts with anorexia athletica.

Leptin, the product of the ob-gene, is specifically released by adipocytes. In addition to its metabolic function it seems to affect the feedback-mechanisms of the hypothalamic-pituitary-gonadal-axis. We studied 13 female juvenile elite gymnasts with anorexia athletica (AA) and 9 female patients with anorexia nervosa (AN) regarding the relation between leptin, fat stores, and the reproductive hormone levels. Leptin levels in females with anorexia nervosa (Tanner stage B4 [median]; mean age: 17.8 +/- 1.7 years) were low (2.9 +/- 2.7 microg/L), and were related to body mass index (BMI) (r = 0.71; p = 0.03) and percentage body fat mass (r = 0.78; p = 0.01). Leptin levels of the elite gymnasts were even more decreased (1.2 +/- 0.8 microg/L) caused by the low amount of fat stores. Leptin correlated with BMI (r= 0.77; p = 0.004) and the percentage body fat mass (r = 0.6; p = 0.04). In elite gymnasts leptin levels correlated with CA showing an age-dependent increase (r= 0.59; p = 0.04). Oestradiol was secreted at a low level in both groups (AN: 25.6 +/- 17.4 microg/L; AA: 24.4 +/- 13.5 microg/L). A delay in menarche and a retarded bone maturation occurred in AA. Our results clearly show that leptin levels are low in restrained eaters. Leptin levels represent the fat stores in the body and play a permissive role for female pubertal development. There is evidence that the mechanisms leading to a dysregulation of the reproductive-axis in patients with AN are comparable with those leading to delayed puberty in juvenile elite gymnasts with AA. This implies that AN and AA are overlapping groups and AA can lead to the development of AN.

Adolescent↗

[Anorexia nervosa in German medical literature 1900 to 1945. The role of anorexia nervosa in the origin of psychosomatic medicine].

German-language publications on anorexia nervosa and Simmonds' disease from between 1900 and 1945 are reviewed in order to trace factors inherent in medical thinking which have mostly hindered German-language medicine in understanding anorexia nervosa. It is demonstrated that a) the few German-language physicians who did describe central and possible characteristics of a.n. (weight-phobia, overactivity, bulimia, self-induced vomiting) were enabled to do so by valuing detailed clinical description, also of psychic characteristics, and an interest in the neuroses; b) the concept of anorexia nervosa was better known than previously assumed, though largely misunderstood; c) typical diagnostic misinterpretations led to typical biases in the description of the syndrome; d) in Germany more than in other countries a.n. was confounded with Simmonds' disease; and e) in addition to other factors, one reason for this lay in the 'holistic' ideal of psychosomatic medicine in the 1930s.

Anorexia Nervosa↗

The discriminative value of psychological characteristics in anorexia nervosa. Clinical and psychometric comparison between anorexia nervosa patients, ballet dancers and controls.

The present controlled study examined anorexic and psychological characteristics of female ballet dancers, who by career choice must focus on thinness, and anorexia nervosa patients. Anorexia nervosa (AN) patients, female ballet (BA) students as well as asymptomatic female controls (AF) were compared with respect to the psychological characteristics: the Drive to Achieve, the Motive to Avoid Failure (Negative Fear of Failure) and the Motive to Achieve (Positive Fear of Failure). The results confirmed previous empirical and clinical findings that the AN group and the BA group can be differentiated from a control group with respect to a heightened Drive to Achieve. However, the Drive to Achieve of AN patients was found to originate in an avoidance of failure (the Negative Fear of Failure), while in BA students this drive was found to stem from a motive to achieve (the Positive Fear of Failure). The findings underline the importance of an evaluation of psychological characteristics in subjects with anorexic symptoms.

Achievement↗

Olanzapine reduces physical activity in rats exposed to activity-based anorexia: possible implications for treatment of anorexia nervosa?

BACKGROUND: Anorexia nervosa (AN) patients often show extreme hypophagia and excessive physical activity. Activity-based anorexia (ABA) is considered an animal model of AN and mimics food restriction and hyperactivity in rats. This study investigated whether treatment with olanzapine (Zyprexa) reduces the development of ABA in rats. The effect of olanzapine treatment in AN patients was also evaluated in a small open-label study. METHODS: Rats were chronically (1 week) infused with olanzapine (7.5 mg/kg) and exposed to the ABA model or ad libitum feeding. Hyperactive AN patients were followed for up to 3 months of olanzapine treatment (5 mg/kg). RESULTS: Olanzapine treatment reduced development of ABA in rats by reducing running wheel activity, starvation-induced hypothermia and activation of the hypothalamus-pituitary-adrenal axis. Olanzapine treatment reduced activity levels of AN patients compared with untreated AN patients, without affecting body weight and plasma leptin levels. CONCLUSIONS: Olanzapine treatment reduced wheel running and thereby diminished development of ABA in rats. Olanzapine treatment also reduced physical activity in hyperactive AN patients in a small open-label study. These data support the need for controlled studies investigating the putative beneficial effects of olanzapine treatment in AN patients.

Adipose Tissue↗

A modern day holy anorexia? Religious language in advertising and anorexia nervosa in the West.

OBJECTIVE: In this review we comment on the media, in particular advertisements and the internet, using religious and moralistic motifs in connection with eating and their possible role in promoting modern-day 'nutritional' consumerism and fundamentalism (diet, discipline and discipleship). METHOD: We have reviewed historically the concept of holy anorexia and have analyzed the pictorial and language content of some representative advertisements. RESULTS: Words used include 'temptation', 'decadent', 'heaven' and 'purity' and suggest a connection with eating and moral values. They also imply eating as either heaven or sin, to be yielded to in both circumstances. CONCLUSIONS: Such messages identifying eating with guilt or reward could precipitate 'atypical' eating disorders in vulnerable subjects, invoking the historical associations with extreme religiosity and anorexia. It is not clear how these 'fundamentalist' trends developed but health educators should be aware of them in dealing with at-risk subjects for eating disorders.

Advertising↗