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Current perspectives on behavioural and cellular mechanisms of illness anorexia.

Here we review our current understanding of the integration of immune, neural, metabolic and endocrine signals involved in the generation of anorexia during acute infection, with the focus on anorexia elicited by peripheral administration of bacterial lipopolysaccharide (LPS). We chose to limit this review to peripheral LPS-anorexia because the mechanisms underlying this response may also be valid for anorexia during other types of acute or chronic infections, with slight differences in the duration of anorexia, levels of circulating concentrations of pro-inflammatory cytokines and hypermetabolism. Evidence so far indicates that LPS-anorexia is a complex response beneficial to host defence that involves both peripheral and central action of pro-inflammatory cytokines, other immune factors, such as prostanoids, and neurotransmitters, such as serotonin. One interesting characteristic of LPS-anorexia is its sexual differentiation, an aspect mainly mediated by the gonadal hormone estradiol. Understanding the behavioural and molecular mechanisms of LPS-anorexia may even provide useful leads for identifying mechanisms of eating disorders in humans.

Animals↗

Psychopathology in anorexia nervosa and depression.

It has been hypothesized that anorexia nervosa is characterized by ineffectiveness, interpersonal distrust, and lack of interoceptive awareness. The Eating Disorder Inventory differentiates patients with anorexia nervosa from weight-preoccupied women on the basis of these subscales. To test further the specificity of these characteristics to anorexia nervosa, the Eating Disorder Inventory scores of 20 adolescent girls diagnosed with anorexia nervosa were compared with those of 21 girls with major depression and 21 girls with both anorexia nervosa and depression. Analyses of variance and discriminant function analysis revealed no significant differences in the scores of the three groups. By 2-year followup, subjects initially diagnosed with only anorexia nervosa showed less psychopathology than those with an additional diagnosis of depression. These findings raise further questions about the overlap between depression and anorexia nervosa and leave open the question of characteristic psychological features in anorexia nervosa.

Adolescent↗

Anorexia nervosa and anorexic-like syndromes in a population-based female twin sample.

OBJECTIVE: The authors explored the epidemiologic characteristics and risk factors of anorexia nervosa and examined the relationship between narrowly defined anorexia nervosa and anorexia-like syndromes. METHOD: Structured interviews were administered to a population-based sample of 2,163 female twins. Anorexia nervosa was diagnosed by computer algorithm ("computer narrow") and by narrow and broad clinical definitions. RESULTS: Lifetime prevalence estimates of 0.51%, 1.62%, and 3.70% were obtained for the computer narrow, clinical narrow, and clinical broad diagnoses, respectively. Dieting status, greater number of years of parental education, low self-esteem, high levels of neuroticism, and maternal overprotectiveness were significantly associated with anorexia nervosa. Both the pattern of comorbidity and the relationship to epidemiologic risk factors suggested an etiologic continuity between narrowly and broadly defined anorexic syndromes. Co-twins of twins with anorexia nervosa were at significantly higher risk for lifetime anorexia nervosa, bulimia nervosa, major depression, and current low body mass index. Significant comorbidity was found between anorexia nervosa and major depression, bulimia nervosa, generalized anxiety disorder, alcoholism, phobias, and panic disorder. CONCLUSIONS: The authors' analyses support the hypothesis of a spectrum of anorexic-like syndromes in women. These syndromes are familial and share familial etiologic factors with major depression and bulimia nervosa.

Adolescent↗

Is impaired set-shifting an endophenotype of anorexia nervosa?

OBJECTIVE: Set-shifting difficulties have been reported in subjects with anorexia nervosa and appear to persist after recovery; therefore, they may be endophenotypic traits. The goals of this study were to investigate whether set-shifting difficulties are familial by examining discordant sister-pairs in comparison with healthy unrelated women and to replicate, with a broader battery, the lack of influence of an acute illness state on neuropsychological performance. METHOD: Forty-seven pairs of sisters discordant for anorexia nervosa and 47 healthy unrelated women who were comparable in age and IQ completed neuropsychological tasks selected to assess set-shifting ability. Analyses of variance with standard errors that are robust against correlations within family clusters were used to compare the groups. Results were adjusted for obsessive-compulsive, anxiety, and depression symptoms. Subjects with acute (N=24) and fully remitted (N=23) anorexia nervosa were compared to assess state versus trait effects. RESULTS: Sisters with and without anorexia nervosa took significantly longer than unrelated healthy women to shift their cognitive set (CatBat task) and demonstrated greater perceptual rigidity (Haptic Illusion task) but did not differ significantly from each other. Women with anorexia nervosa were slower than other groups on Trail Making tasks. Women who had fully recovered from anorexia nervosa made significantly fewer errors than those with acute anorexia nervosa on the Trail Making alphabet task, but these subgroups did not differ on other measures. CONCLUSIONS: Both affected and unaffected sisters had more set-shifting difficulties than unrelated healthy women. This finding, together with the replicated finding that set-shifting difficulties persist after recovery, suggests that set-shifting difficulties are trait characteristics and may inform the search for the endophenotype in anorexia nervosa.

Adult↗

The incidence of anorexia nervosa on Curaçao.

OBJECTIVE: Although anorexia nervosa was once thought to occur only in affluent societies, cases have now been documented across the globe. To examine whether anorexia nervosa emerges in societies undergoing socioeconomic transition, the authors studied the incidence of anorexia nervosa on the Caribbean island of Curaçao. METHOD: The authors contacted the full range of community health and service providers on Curaçao, including dietitians, school counselors, and all 82 general practitioners. They also studied inpatient records for 84,420 admissions to Curaçao General Hospital and two private hospitals in 1995-1998. Probable-incident subjects were interviewed. RESULTS: The incidence rates in 1995-1998 per 100,000 person-years for anorexia nervosa on Curaçao were 1.82 (95% confidence interval [CI]=0.74-2.89) for the total population and 17.48 (95% CI=4.13-30.43) for the high-risk group of 15-24-year-old females. No cases were found among the majority black population. For the Curaçao mixed and white population, the incidence rate per 100,000 person-years for anorexia nervosa was 9.08 (95% CI=3.71-14.45). CONCLUSIONS: The overall incidence of anorexia nervosa on Curaçao is much lower than in the affluent societies of the United States and Western Europe. Within Curaçao, sociocultural factors appear to be associated with differential incidence rates of anorexia nervosa. The incidence of anorexia nervosa among the majority black population is nil, while the incidence among the minority mixed and white population on Curaçao is similar to that of the United States and the Netherlands.

Adolescent↗

Fertility and reproduction in women with anorexia nervosa: a controlled study.

BACKGROUND: Women who have anorexia nervosa may experience difficulties with fertility and reproduction. METHOD: We examined fertility and reproductive history in 66 women who had a history of anorexia nervosa (DSM-III-R) and 98 randomly selected community controls as part of a follow-up investigation examining the course of anorexia nervosa. RESULTS: Although women with a history of anorexia nervosa and controls did not differ on rate of pregnancy, mean number of pregnancies per woman, or age at first pregnancy, women with anorexia nervosa had significantly more miscarriages and cesarean deliveries, and the offspring of women with anorexia nervosa were significantly more likely to be born prematurely and were of lower birth weight than offspring of controls. There were no differences between women with active versus remitted anorexia nervosa on any of these measures; however, offspring of anorexic women with no history of bulimia nervosa had significantly lower body weight than offspring of anorexic women with a lifetime history of bulimia nervosa. CONCLUSION: Our results argue for intensive prenatal care for women with both active and remitted anorexia nervosa to ensure adequate prenatal nutrition and fetal development.

Adult↗

Helicobacter pylori infection: a new cause of anorexia in peritoneal dialysis patients.

OBJECTIVE: Helicobacter pylori (HP) infection has frequently been found in dialysis patients. Chronic infections induce overproduction of pro-inflammatory substances. Inflammation has been associated with cachexia and anorexia. We explored the relationship between HP infection, anorexia, and malnutrition in peritoneal dialysis (PD) patients. PATIENTS AND METHODS: The study included 48 clinically stable PD patients divided into four groups: HP+ with anorexia (group I, n = 12); HP+ without anorexia (group II, n = 4); HP- with anorexia (group III, n = 5); and HP- without anorexia (group IV, n = 27). Infection with HP was diagnosed by breath test. Anorexia was evaluated using a personal interview and an eating motivation scale (VAS). The VAS included five questions that are answered before and after eating. The questions concern desire to eat, hunger, feeling of fullness, prospective consumption, and palatability. Biochemical markers of nutrition and inflammation were also determined. RESULTS: At baseline, group I showed lower scores for desire to eat, hunger sensation, prospective consumption, and palatability. They also showed lower lymphocyte counts, prealbumin, transferrin, serum albumin, normalized equivalent of protein-nitrogen appearance (nPNA), and residual renal function (RRF). In addition, the same group showed higher levels of C-reactive protein (CRP) and more sensation of fullness than the remaining groups. In the entire series, we found significant linear correlations between the following markers of nutrition and certain questions on the VAS: albumin with before-lunch desire to eat (r = 0.38, p < 0.05), and prealbumin with before-lunch hunger (r = 0.41, p < 0.05) and after-lunch hunger (r = -0.35, p < 0.05). Negative linear correlations were found between albumin and fullness before lunch (r = -0.45, p < 0.01), and between prealbumin and before-lunch desire to eat (r = -0.39, p < 0.05). Negative linear correlations were also seen between CRP and albumin (r = -0.35, p < 0.05) and between CRP and prealbumin (r = -0.36, p < 0.05). Similarly, CRP showed a negative correlation with before-lunch desire to eat (r = -0.38, p < 0.05) and afterlunch desire to eat (r = -0.45, p < 0.01). After HP eradication, group I showed a significant increase in markers of nutrition and in VAS scores for almost all questions. Simultaneously, they showed a decrease in CRP level. Significant differences were also found in lymphocyte count (1105 +/- 259.4 cells/mm3 vs 1330.8 +/- 316 cells/mm3, p < 0.05), nPNA (0.9 +/- 0.16 g/kg/day vs 1.07 +/- 0.3 g/kg/day, p < 0.05), prealbumin (26.7 +/- 6.5 mg/dL vs 33.9 +/- 56.6 mg/dL, p < 0.01), albumin (3.48 +/- 0.3 g/dL vs 3.67 +/- 0.35 g/dL, p < 0.05), CRP (1.16 +/- 1.14 mg/dL vs 0.88 +/- 1.2 mg/dL, p < 0.054), before-lunch desire to eat (56.6 +/- 6.8 vs 72.2 +/- 4, p < 0.001), after-lunch desire to eat (5.4 +/- 2.6 vs 12.3 +/- 2, p < 0.01), hunger before lunch (55.4 +/- 5.4 vs 73.1 +/- 4.6, p < 0.001), hunger after lunch (5.8 +/- 2.9 vs 11 +/- 4, p < 0.01), fullness before lunch (36.6 +/- 10.3 vs 18.7 +/- 8.8, p < 0.001), consumption after lunch (5 +/- 4.7 vs 17.5 +/- 18, p < 0.05), and palatability (61 +/- 5.3 vs 74.1 +/- 4.1, p < 0.001). CONCLUSION: Infection with HP is associated with anorexia, inflammation, and malnutrition in PD patients. Eradication of HP significantly improves this syndrome. Residual renal function seem to have a protective effect on appetite preservation. The present study supports the hypothesis of the involvement of inflammation in the pathogenesis of malnutrition in PD patients.

Adult↗

[Anxiety disorders in children suffering from anorexia nervosa].

AIM: The basic aim of the study was the estimation of comorbidity of anxiety disorders (including obsessive-compulsive disorders) and anorexia nervosa. The next aim was to make out whether and what kind of influence is exerted on them by environmental (especially the family's) and children's own conditioning. A group of 30 children (the average age - 13.5 years), 27 girls and 3 boys treated for the first episode of anorexia nervosa was considered. METHOD: Structured interview from patients as well as their parents, clinical observation, psychiatric and psychological investigation with the use of The Depression Rating Scale for Children (Elva o. Poznansky and comp.), The Hamilton Depression Rating Scale and The Children's Yale-Brown Obsessive-Compulsive Scale. Results were worked out with the help of statistical methods. RESULTS: The comorbidity of anxiety disorders, OCD and anorexia nervosa in the considered group was frequently observed. Anxiety disorders were observed in the group of 16.7% patients in which 6.7% suffered from generalized anxiety disorders and 10% - from social phobia. According to the anamnesis - 40% of the investigated children, suffered from separation anxiety in the past, 13% - manifested social phobia and 10% - experienced generalized anxiety disorders. Together, during the whole life of those studied, anxiety disorders were observed in 40% of the children. Statistically, in the examined group, depression was significantly frequent amongst children suffering from anxiety disorders and anorexia nervosa (p<0.01). The comorbidity of OCD and anorexia nervosa appeared in 13.3% of the cases. As for intensity--in one case it was extremely severe, in another one--moderate and in two other cases--mild. In the investigated group of children OCD appeared in the restricting subtype of anorexia nervosa. All children with OCD and anorexia nervosa suffered from severe depression syndromes. CONCLUSIONS: In the considered group of children suffering from anorexia nervosa the number of biological as well as psychological events which could predispose to anxiety disorders (including OCD) was found.

Adolescent↗

[Pathogenetic and therapeutic aspects of secondary anorexia].

Anorexia is an often underrated symptom in the clinical management of patients suffering from chronic diseases. Moreover, the anorexia accompanying chronic diseases (secondary anorexia) is often confused with anorexia nervosa, a typically neuropsychiatric disorder involving completely different pathogenic mechanisms and therapeutic strategies. Secondary anorexia is one of the main factors responsible for the development of malnutrition, which in turn negatively affects patient morbidity and mortality. Different mechanisms have been proposed to explain the pathogenesis of secondary anorexia. However, consistent experimental and clinical evidence seems to point to hypothalamic serotonergic system hyperactivity as a preeminent cause; this hyperactivity appears to be triggered by enhanced brain availability of tryptophan, the aminoacid precursor of serotonin. The hyperactive hypothalamic serotonergic system might also represent the final effector where different regulatory and modulating pathways, including cytokines, converge. The involvement of tryptophan and the hypothalamic serotonergic system is further supported by the effectiveness of a therapeutic strategy, based on the inhibition of tryptophan entry into the brain, in increasing the food intake of anorectic patients. Although these results represent an encouraging approach to the treatment of secondary anorexia, with possible beneficial effects on the nutritional status of patients, they need to be validated in larger trials.

Adolescent↗

Medical findings in outpatients with anorexia nervosa.

BACKGROUND: Approximately 0.5% to 1% of college-aged women have anorexia nervosa and most of them live in the community. However, few clinical data exist regarding community-dwelling women with anorexia nervosa. The objective of this study was to determine the prevalences of common medical findings for these women. METHODS: Cross-sectional, community-based study of 214 women with anorexia nervosa as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Participants were recruited through advertisements and community-based referrals to a study investigating skeletal health in outpatients with anorexia nervosa. RESULTS: The prevalences of medical findings among the 214 participants were as follows: anemia, 38.6%; leukocytopenia, 34.4%; hyponatremia, 19.7%; hypokalemia, 19.7%; bradycardia, 41.3%; hypotension, 16.1%; hypothermia, 22.4%; elevation of alanine aminotransferase concentration, 12.2%; osteopenia, 51.7%; osteoporosis, 34.6%; and primary amenorrhea, 14.8%. Moreover, 30% of the women reported histories of bone fractures. Except for leukocytopenia (P = .01), bone loss (P = .04), and bradycardia (P = .01), the probability of specific medical findings could not be predicted by the degree of undernutrition. CONCLUSIONS: These results demonstrate a high prevalence of medical findings in community-dwelling women with anorexia nervosa. Therefore, women with anorexia nervosa should be carefully followed up with regular physical examinations and laboratory assessments. In addition, low weight, particularly in conjunction with the abnormalities reported, should prompt the consideration of a diagnosis of anorexia nervosa.

Absorptiometry, Photon↗

Family and individual therapy in anorexia nervosa. A 5-year follow-up.

BACKGROUND: There is evidence that specific psychological treatments are effective in patients with eating disorders. Our goal was to determine by means of a controlled trial whether psychological treatments, previously found to be effective in anorexia nervosa, gave rise to enduring benefits. METHODS: A 5-year follow-up was conducted on patients who had participated in a previous trial of family therapy for anorexia and bulimia nervosa. Family therapy or individual supportive therapy had been administered to 80 outpatients for 1 year beginning on discharge from hospital after weight restoration. The 80 patients had been subdivided into 4 prognostically homogeneous groups of which 2 turned out to be the most important: patients with early onset and short history of anorexia nervosa, and patients with late-onset anorexia nervosa. At the 5-year follow-up, the efficacy of the outpatient therapies was again assessed by the maintenance of weight, and the categories of general outcome and dimensions of clinical functioning defined by the Morgan-Russell scales. RESULTS: Significant improvements were found in the group of 80 patients as a whole, mainly attributable to the natural outcome of anorexia nervosa, and most evident in the early onset and short history group, as expected. Within 2 of the prognostic groups, significant benefits attributable to previous psychological treatments were still evident, favoring family therapy for patients with early onset and short history of anorexia nervosa and favoring individual supportive therapy for patients with late-onset anorexia nervosa. CONCLUSIONS: Much of the improvements found at a 5-year follow-up can be attributed to the natural outcome of the illness. Nevertheless, it was still possible to detect long-term benefits of psychological therapies completed 5 years previously.

Adolescent↗

Risk factors for anorexia nervosa: three integrated case-control comparisons.

BACKGROUND: Many risk factors have been implicated in the development of anorexia nervosa. Little is known about their relative contributions, nor in most cases is it clear whether they are specific to anorexia nervosa or risk factors for all eating disorders or for psychiatric disorder in general. METHODS: We used a case-control design involving the comparison of 67 female subjects with a history of anorexia nervosa with 204 healthy control subjects, 102 subjects with other psychiatric disorders, and 102 subjects with bulimia nervosa. A broad range of risk factors was assessed by interview. RESULTS: The subjects with anorexia nervosa and the healthy controls differed in their exposure to most of the putative risk factors. There was no greater exposure to factors that increased the likelihood of dieting, once the influence of other classes of risk factors had been taken into account. Premorbid perfectionism and negative self-evaluation were especially common and more so than among the general psychiatric controls. Parental obesity and an early menarche, together with parental psychiatric disorder, distinguished those with bulimia nervosa from those with anorexia nervosa. CONCLUSIONS: There appears to be a broad range of risk factors for anorexia nervosa and bulimia nervosa, some of which are shared with other psychiatric disorders. Factors that increase the likelihood of dieting seem to have more important influence as risk factors for bulimia nervosa than anorexia nervosa. Perfectionism and negative self-evaluation appear to be particularly common and characteristic antecedents of both eating disorders.

Adolescent↗

Secular trends in the incidence of anorexia nervosa: integrative review of population-based studies.

OBJECTIVE AND METHOD: Aggregating across retrospective cohort samples, this integrative review synthesizes the findings of 12 cumulative incidence studies (45 hypotheses) on anorexia nervosa secular trends. RESULTS: (1) The female/male anorexia incidence rate ratio was estimated to be 8.20, 18.46 versus 2.25 cases per 100,000 per year, p < .05; (2) female teenagers experienced anorexia at a rate fivefold greater than other women, 50.82 versus 10.37 incident cases per 100,000 per year, p < .001; (3) no secular trend or change in the incidence of anorexia was observed among teenagers, while a near threefold increase was observed over the past 40 years among women in their 20s and 30s, 6.28 (1950-1964) versus 17.70 (1980-1992) cases per 100,000 per year, p < .05; and (4) the two cohort characteristics of age, and the age by year interaction accounted for nearly two thirds of the variability among anorexia incidence estimates, R2 = .614, F(2,27) = 21.49, p < .001. After the two factors of age and the Age x Year interaction were accounted for, none of the other study characteristics, including study year(s), were found to be significantly associated with anorexia incidence, that is, a main effect of time was not observed. DISCUSSION: The integrative evidence across the population-based epidemiologic studies covering 40 years in this field suggests strongly that, overall, the incidence of anorexia nervosa, particularly among those very young women at greatest risk of experiencing it, has not increased significantly. However, the risk does seem to have increased significantly among women in their 20s and 30s.

Adolescent↗

Pattern of birth in anorexia nervosa. I: Early-onset cases in the United Kingdom.

OBJECTIVES: Previous studies suggest that adults with anorexia nervosa are more likely to be born in spring and early summer. This study examines whether this pattern of birth is true of early-onset anorexia nervosa, and whether there is a relationship between environmental temperature at assumed time of conception and a later diagnosis of anorexia nervosa. METHOD: The population were children and adolescents with diagnoses of anorexia nervosa (N = 259) or "other eating disorders" (N = 149). Distribution of births across the year was compared between groups and relative to standard population norms. Temperature at assumed time of conception was taken from meteorological records. RESULTS: There was a significant preponderance of births among those with anorexia nervosa between April and June, compared with the other months of the year and with the "other eating disorders" group. Anorexia nervosa was also associated with higher environmental temperature at assumed time of conception. CONCLUSIONS: Among early-onset cases in the United Kingdom, patients with anorexia nervosa are more likely to be born between April and June, and to be conceived during warmer months. A tentative "temperature at conception" hypothesis is advanced to explain these findings and to generate further research.

Adolescent↗

Males with anorexia nervosa: a controlled study of eating disorders in first-degree relatives.

OBJECTIVE: To compare lifetime rates of full and partial anorexia nervosa and bulimia nervosa in first-degree relatives of males with anorexia nervosa and in relatives of never-ill comparison subjects. METHODS: Rates of eating disorders were obtained for 747 relatives of 210 probands from personal structured clinical interviews and family history. Best-estimate diagnoses were determined blind to proband diagnosis and pedigree status. RESULTS: Full and partial syndromes of anorexia nervosa aggregated in female relatives of ill probands. For the full syndrome of anorexia nervosa, the crude relative risk was 20.3 among female relatives and for partial syndrome anorexia nervosa, the crude relative risk was 3.3. In contrast, bulimia nervosa was relatively uncommon among relatives of ill probands. CONCLUSION: Although anorexia nervosa in males is exceedingly rare, there is a pattern of familial aggregation that is highly similar to that observed in recent family studies of affected females. On the basis of these findings, there is no evidence that familial-genetic factors distinguish the occurrence of anorexia nervosa in the two sexes.

Adolescent↗

Serum immunoreactive leptin concentrations in patients with anorexia nervosa before and after partial weight recovery.

Leptin, the product of the ob gene, is a recently discovered hormone secreted by adipocytes. Serum leptin concentrations increase in correlation with the percentage of body fat, but besides that little is known about the physiological actions of leptin in humans. In order to understand the role of leptin in severe malnutrition, in the present work 10 patients recently diagnosed with anorexia nervosa were studied both before and 2 months later, after partial weight recovery, and were compared with 18 normal-weight women as controls. Leptin was measured by a newly developed radioimmunoassay and both IGF-I and IGFBP-3 were measured by commercial radioimmunoassays. The mean (+/-SE) serum leptin concentrations (in microgram/liter) were 18.1 +/- 2.0 in control women with BMI of 21.1 +/- 0.3, significantly higher (P < 0.01) than that in the anorexia nervosa patients at diagnosis (2.2 +/- 0.1, BMI 15.3 +/- 0.6). These differences were also observed in IGF-I values (microgram/liter) that were 228.0 +/- 14.6 in controls and 157.4 +/- 28.7 in anorexia nervosa patients (P < 0.02). No differences were observed in IGF-BP3. After treatment, patients with anorexia nervosa experienced an increase in BMI (17.1 +/- 0.5, P < 0.0001 vs before) although they were still underweight. The partial recovery in weight led to a complete normalization of IGF-I levels (214.0 +/- 21.0 micrograms/liter) and to an enhancement in leptin levels (3.3 +/- 0.5 micrograms/liter; P < 0.03 vs before treatment), though still lower than those in normal-weight women (P < 0.05). Individually analyzed, a large dispersion was observed in control subjects, with leptin levels ranging from 5.5 to 38.7 micrograms/liter, while in all anorexia nervosa patients leptin levels were under 3 micrograms/liter. A treatment-induced increase in body weight led to an increase in leptin levels in 7 out of the 10 anorexia nervosa patients studied and the 3 patients with no increase in leptin were all initially under the 14.5 BMI. In conclusion, leptin levels are severely reduced in anorexia nervosa patients with severe malnutrition, and a significant rise occurred after partial weight recovery. There seems to be a level of BMI below which leptin levels do not drop further but also do not increase despite weight gain. While IGF-I reflects the energy intake of the previous few weeks, the serum leptin concentration reflects the true status of the adipose stores, a fact that has useful clinical implications.

Adult↗

Anorexia nervosa: evidence for a genetic basis.

This paper reports the preliminary results of a combined twin and family study of anorexia nervosa. Fifty-six per cent of the 25 female monozygotic (MZ) twin pairs and 5% of the 20 female dizygotic (DZ) twin pairs were concordant for anorexia nervosa. Nearly 5% of other female first degree relatives also had a history of anorexia nervosa. Analysis of data from the Eating Disorders Questionnaire (EDI) given to the twins and data as to weight loss, length of amenorrhoea and other characteristics of anorexia nervosa, together with the twin and family data, supports the hypothesis that genetic factors are very significant in the aetiology of anorexia nervosa. Analysis of this data using established techniques of psychiatric genetics suggested that up to 80% of the variance in liability to anorexia nervosa may be accounted for by genetic factors. The problems of this type of analysis are discussed as is the background to the genetics of weight and appetite control. A genetic/environmental model accounting for the features of anorexia nervosa is proposed.

Adult↗

Steroids and neuroendocrine function in anorexia nervosa.

Anorexia nervosa is a primarily psychiatric syndrome of self-induced weight loss due to an intense fear of becoming obese. Numerous endocrine abnormalities occur in anorexia nervosa patients, and in many respects these alterations reflects the endocrinology of reduced energy intake. However, the basic mechanisms of those alterations are far from being understood. In an attempt to understand the disrupted mechanisms of the hypogonadotropic hypogonadism of the anorectic state, we studied 10 anorectic women in the acute phase of their illness; all met the DSM III criteria. On each patient, two tests were performed with either saline as control or infusion of the opioid antagonist naloxone, and both LH and FSH levels were measured. Four mg of naloxone as bolus was used, followed by a naloxone infusion of 2 mg/h for 4 h. Compared with the pattern of normal women, naloxone did not increase in the anorectic patients either LH or FSH levels nor pulsatility. This result suggests that endogenous opioid peptides are not implicated in the low gonadotropic situation of anorexia nervosa. An alternative explanation could be that the low estrogenic "milieu" of these patients could mask the opioid action. To test this second possibility, another group of 7 anorectic women after partial weight recovery were challenged with estrogen administration. Compared with the pattern of normal women volunteers, all the anorectic patients but one presented an abnormal response in both LH and FSH levels after estrogen administration. In fact, the negative feedback and the delayed positive feedback of LH after estrogen were absent in these patients. Interestingly enough, the only patient with near-normal LH response to estrogen was considered fully recovered by the Psychiatric Unit. Several alterations in the hypothalamic-pituitary-adrenal axis has been reported in anorexia nervosa. Seven anorectic patients and 7 aged-matched women were challenged by ACTH 1-24, 250 micrograms (i.v.) and the ratio of increments in adrenal steroid products to precursors monitored. ACTH-induced increments in cortisol with respect to increments in 17-OH-progesterone was similar in anorectics and controls. On the contrary, the ratio of increments of androstenedione with respect to increments in 17-OH-progesterone were greater in anorexia nervosa than controls. These results suggest that in anorexia nervosa the 11-beta-21-alpha-hydroxylase system is normal but a deficient 17-20 desmolase system is present. Finally, the altered pattern of GH secretion in anorexia was studied using GHRH (1 microgram/kg) as stimulus of pituitary GH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

Amenorrhea↗