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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

[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

Long-term outcome of 151 cases of anorexia nervosa. The Copenhagen Anorexia Nervosa Follow-Up Study.

One hundred and fifty-one patients (140 females - 11 males) with anorexia nervosa (AN) from three departments (child psychiatry, psychiatry, and internal medicine) were re-examined 4-22 years (average 12.5 years) after their first contact with the Rigshospital in Copenhagen. During the years 1960-76 the number of referrals was on the increase, and relatively more patients were treated in the psychiatric departments at the end than at the beginning of the period. Mean age was 16.6 years at onset, 19.0 years at primary contact. Mean weight loss was 32%. Mean duration of treatment was 12 months. Differences between the three departments concern especially age, sex, and duration of treatment. Mean age at follow-up was 31.0 years (range 16-63 years) for surviving probands. Follow-up information originated from semi-structured personal interviews (in 80% of surviving probands) together with register data on all probands, supplemented by extensive hospital data. Nine patients (6%), including six who committed suicide, died on the average 7.3 years after primary contact (average age 27.1 years). The mortality rate was 0.5% per year. At follow-up one fourth of the surviving probands had AN and one fourth suffered from other psychiatric disorders, while one half were free from mental illness. There were no significant differences in outcome between the three departments. As a whole, the group experienced a social decline. It is concluded that a substantial part of this group of AN patients had a poor prognosis with a tendency towards chronicity, despite relatively long and intensive treatment, but, on the other hand, about one half of the probands seemed to be healthy and well functioning.

Adolescent

Anorexia and bulimia in anorexia nervosa: a study of psychosocial functioning and associated psychiatric symptomatology.

Seventeen fasting patients with anorexia nervosa and 15 who also binged were compared in terms of their psychosocial functioning and associated psychiatric symptomatology, using the Delusions Symptoms and States Inventory (Foulds & Bedford, 1975). Both groups scored very highly on the state of anxiety, depression, and elation sets of the DSSI, but less highly on the compulsive and ruminative symptoms sets and on the phobic dissociative and conversion symptom sets. The bingeing anorexic group was significantly older and heavier than the fasting group and experienced more feelings of self-harm and guilt. The bingeing group reported sexual interference during childhood, and currently experienced a desire to vomit during sexual activity to a significantly greater degree than the fasting group.

Adolescent

[Dysperception of body image and dysmorphophobias in mental anorexia. Apropos of 115 cases involving both sexes. I. Altered mechanisms of perception in mental anorexia].

We noted frequency of body-image disturbance (BID) and dismorphophobias (DPP) in 97 girls and 8 boys among 107 girls and 8 boys with Anorexia Nervosa (AN), seen since 1973 and coming up semiologic criterions of Laboucarie and Dally & Sargant. 91,5% of the girls and 7 out of 8 boys presented a BID at one time of their evolution. The other ones did not form a characteristic group. BID prevailed in no-perception of emaciation. No-perception of overweight was exceptional. That of variations of weight was frequent, explaining to need objective elements to measure real volume. BID seems to result from an incapacity to integrate well individually perceived details into a coherent image. Its apparition signals starting of AN, and it is a fundamental criterion of evolutivity. It's not frequent it's extended to body-image disperception of the close people, but it is often associated to an increase of mental representation of ingested feed volume.

Adolescent

[Dysperception of body image and dysmorphophobias in mental anorexia. Apropos of 115 cases involving both sexes. II. Dysmorphophobias in mental anorexia].

Study of DPP extended over 2 groups selected as following: It was prospective in every patient seen between July 1976 and May 1977 (systematic study: SS: 35 girls and 2 boys). It was retrospective in another group before selected for importance of DPP (no systematic study: NSS: 34 girls and 6 boys). DPP were distributed into Dalpha (fear of any weight recovery), Dbeta (obsessing repercussion of a real defect, amplified in its perception) and Dgamma (delirious and obsessing conviction of a physical anomaly). We researched correlations with the type of AN (fixity or recession to childhood), premorbid weight-height ratio, overweight of the same-sex parent, important problems towards sexuality (ASC = Absolute sexual conflict = An entirely caused by a sexual difficulty, or PSC = Partial Sexual Conflict = difficulty towards sexuality when insuffisant to explain AN, or no sexual conflict), attitude towards pregnancy in cases of big-belly DPP. Every DPP were DPP of localized or generalized obesity. Dalpha is constant and pathognomonic. In females of SS, 37% presented Dbeta and 5% Dgamma before AN, 25% Dbeta and 11% Dgamma during AN. Among the 8 boys of the 2 studies, 3 presented Dgamma before AN, and everyone expressed their obsessing fear of "ugly grease". In 20% girls and 50% boys, explained aim of loss of weight was to "wipe out" the anomally DPP emphasized. We did not find any correlation between generalized DPP and studied elements, particularly with sexual conflicts (22% of our cases). The more frequent localized DPP was "big-belly"-DPP, always associated with overweight of the same sex parent, but as for other localized DPP, without any correlation with sexual conflicts, problems towards the father, neither reject of pregnancy.

Adolescent

Delayed pituitary hormone response to LRF and TRF in patients with anorexia nervosa and with secondary amenorrhea associated with simple weight loss.

The qualitative and quantitative responses of LRF-induced LH and FSH release and TRF-induced TSH and Prolactin (PRL) release were evaluated in 21 patients with anorexia nervosa, 19 patients with secondary amenorrhea associated with simple weight loss (SWL) who did not fulfill the psychologic criteria for anorexia nervosa, and 7 normal women in the early follicular phase of the menstrual cycle. Basal plasma LH and FSH were significantly lower in the anorexia nervosa group compared to the SWL group and normals (P less than 0.05). The LRF-induced integrated LH responses, however, were the same in the 3 groups and the integrated FSH responses were greater in the underweight groups when compared to normal. The time of the peak LH response (mean+/-SE) was signifantly delayed (P less than 0.01) in both the anorexia nervosa (49 +/- 6.1 min) and SWL (28 +/- 2.5 min) groups when compared to normal (17 +/- 2.3 min). The time of the FSH response was significantly delayed (P less than 0.05) in anorexia nervosa (95 +/- 9.6 min) when compared to normals (35 +/0 7.9 min) and SWL patients (62 +/- 11.7 min). Normal basal TSH and PRL and normal peak TSH and PRL responses to TRF were found in anorexia nervosa. The time of the TSH and PRL peak (56+/-8.9 and 36+/-3.6 min,, respectively) in anorexia nervosa was significantly later than normal (26 +/- 1.7 and 36 +/- 3.6 min respectively) (P less than 0.01). It is concluded that despite normal quantitative response to releasing hormones, there are abnormally delayed responses in both anorexia nervosa and SWL patients. The SWL responses were intermediate between those of the anorexia nervosa group and normals. The constellation of normal quantitative but abnormal kinetic LRF and TRF responses supports the hypothesis that the endocrine changes seen in anorexia nervosa are consistent with hypothalamic dysfunction.

Adolescent

Low serum triiodothyronine (T3) and hypothyroidism in anorexia nervosa.

Measurements of serum thyroid hormones were compared in 22 patients with typical anorexia nervosa and 22 euthyroid control subjects. Serum total triiodothyronine (T3) was (mean +/- (SE) 62.1 +/- 7.1 ng/100 ml in anorexia patients and 115.2 +/- 8.4 ng/100 ml in control subjects (P less than 0.001). Serum adjusted thyroxine (T4Adj) was significantly different in the anorexia (7.1 +/- 0.4) and control (8.2 +/- 0.4) groups. Serum T3 was subnormal in 63% and T4Adj subnormal in 36% of the 22 anorexia patients. The mean serum T4/T3 in anorexia patients (158 +/- 19) was higher than that in the control subjects (88 +/- 5.5, P less than 0.005) or in 18 patients with hypothalamic or pituitary hypothyroidism (77.9 +/- 10.1, P less than 0.001). Following weight gain in 6 anorexia patients, there was a significant rise in serum T3 without change in T4Adj concentration. The Achilles reflex half-relaxation time (ART) in 38 anorexia patients was 348.6 +/- 10 msec compared with 280 +/- 30 msec in 168 normal age-matched subjects (P less than 0.001), and was prolonged (greater than 340 msec) in 65% of these 38 patients. In 18 anorexia patients with measured ART, T3 and T4Adj, the mean ART was longer 376.1 +/- 20 msec) in 10 with subnormal T3 than in 8 patients with a normal T3 (294.7 +/- 13.2 msec, P less than 0.01). There was no significant difference in the mean ART between patients with a normal or low serum T4Adj. Administeration of oral T3 40 mug/day for 4 weeks to 11 anorexia patients caused a significant reduction (P less than 0.001) in mean ART of 108.7 +/- 9.6 msec compared with 17.7 +/- 3.3 msec in 18 normal subjects. There was a normal peak serum TSH and a rise in mean total serum T3 of 47 +/- 12 ng/100 ml (range 11-100 ng/ml) in 7 of 8 patients following 200 mug of iv thyrotropin releasing hormone (TRH). The fall in serum TSH was delayed in 6 patients. Assessment of hypothalamic control of thyroid function in 3 patients using the method of thyroidal iodide release (TIR) showed impairment of the normal diurnal variation and response to administered glucocorticoids. In the absence of a space-occupying pituitary lesion, the TRH and TIR data suggest a central inhibition of thyroid function, possibly by impairment of hypothalamic TRH release. In addition, a probable decrease of peripheral T4 to T3 conversion leads to low serum T3 concentrations. The prolonged basal ART and the marked ART reduction in response to T3 administration is attributed to correction of tissue thyroid hormone deficiency in the anorexia patients.

Achilles Tendon

Human pancreatic polypeptide responsiveness to insulin-induced hypoglycemia in anorexia nervosa.

Patients with anorexia nervosa occasionally suffer from hypoglycemic comas. We investigated the role of human pancreatic polypeptide (HPP) in insulin-induced hypoglycemia (0.1 U/kg of regular insulin). Ten female patients with anorexia nervosa (20.7 +/- 2.0 years, mean +/- SEM; 34.9 +/- 1.7 kg, mean +/- SEM) and 8 age-matched female controls (20.9 +/- 0.6 years, 51.5 +/- 0.8 kg) were tested. In the patients with anorexia nervosa, testing was performed before and after the restoration of body weight (45.0 +/- 0.8 kg). There was no significant difference in glucose nadir between patients with anorexia nervosa and the control subjects. However, glucose recovery from nadir was delayed in patients with anorexia nervosa. In anorexia nervosa patients, the plasma pancreatic glucagon responses to insulin-induced hypoglycemia did not differ from those of the controls. Results also showed, however, that HPP responses to insulin-induced hypoglycemia were significantly higher in patients with anorexia nervosa than in controls (p less than 0.01). The increased HPP responses were still present after the restoration of body weight in anorexia nervosa patients. A complete body weight recovery or a longer period of time may be required to normalize the HPP response to insulin-induced hypoglycemia in patients with anorexia nervosa, after the restoration of body weight.

Adolescent

Atypical endogenous opioid systems in mice in relation to an auto-addiction opioid model of anorexia nervosa.

We have proposed that the atypical opioid system in the mouse may be representative of that in the anorexia nervosa patient and may account for a biological predisposition to the disorder. This is in the context of our auto-addiction model of anorexia nervosa in which endogenous opioids play a critical role in its etiology. Morphine activation of the endogenous opioid systems increases food intake and causes sedation in most species, including normal humans and rats. In contrast in BALB/C mice, morphine causes anorexia and hyperactivity, which we suggest may be true in the anorexia nervosa patient. A variety of atypical opioid systems have been demonstrated in different mouse strains, based on other responses. The present study examines these strains with reference to the responses relevant to our anorexia nervosa model. Three patterns are described--anorexia with hyperactivity (BALB/C and C57BL/6J mice), anorexia without hyperactivity (DBA/J mice), and a biphasic curve with hyperphagia at low doses and anorexia and hyperactivity at higher doses (CF-1 mice). Only female mice were used. These atypical opioid systems may reflect a spectrum of biological predispositions to the disorder. These strain differences may also provide useful correlations of the genetic determinants of various opiate responses and provide useful comparisons in characterizing the essential features responsible for the atypical responses.

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: 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