A. Wakeling

Abnormal eating attitudes in London schoolgirls--a prospective epidemiological study: outcome at twelve month follow-up.

The occurrence and course of eating disorder in a large representative population of 15-year-old London schoolgirls has been assessed using a two-stage survey methodology. Attempts to control weight were common and often transient. Dieting was in the great majority of girls found to be a benign practice without progression to more extreme concerns about food and weight. However, a small proportion of dieters did become cases and formed the majority of new cases found at follow-up. The relative risk of dieters becoming cases was eight times that of non-dieters. Many factors conventionally associated with eating disorder were associated more with attempting weight control than caseness. These included pre-morbid personality, pre-morbid obesity and family weight pathology. Other factors, including social class, career choice and psychosexual development, had no association either with attempting weight control or caseness.

Cognitive functioning, weight change and therapy in anorexia nervosa

Anorexia nervosa is associated with impairments in cognitive function which have been hypothesized to be fundamentally attentional in nature. The current study investigated whether therapy and weight gain affect these impairments. A group of anorexics (N = 12) completed a battery of cognitive performance tasks and self-report measures of psychopathology on three occasions, over the course of 12 weeks of in-patient treatment. A non-clinical control population (N = 17) completed the same measures. The anorexics improved on all measures of psychopathology and affective state as a result of therapy. Anorexics displayed poorer recall, reaction times, and motor speed than the control subjects. Although there was a gain in weight over the course of therapy, there was no corresponding improvement in cognitive performance. Impaired task performance in anorexics was not directly related to their psychopathology or affective state.

STRUCTURAL BRAIN CHANGES IN PATIENTS WITH ANOREXIA-NERVOSA

Twenty-five patients with anorexia nervosa were compared with 17 normal healthy control subjects in terms of their cerebral computed tomographic (CT) scan appearances. The patients displayed significantly greater ventricular and sulcal enlargement when compared to control subjects. There were no relationships between the CT scan appearance and clinical indices of illness severity or weight loss in the patient group. In 14 patients who had repeat scans after attaining normal body weight, no significant change was observed in the ventricular appearance, but there was a significant lessening in the degree of sulcal widening.

Vitamin D deficiency and low osteocalcin concentrations in anorexia nervosa.

The calcium, vitamin D, and osteocalcin concentrations were investigated in 17 patients with anorexia nervosa. Serum 25-hydroxyvitamin D (25 OHD) concentrations below normal were observed in 15 (88%); only two patients has serum 1,25 dihydroxycholecalciferol (1,25(OH)2D) concentrations below normal. Serum parathyroid hormone (PTH) concentration was also normal in all except these two patients. Serum osteocalcin concentration was below normal in seven of 14 patients. Although a low concentration of serum 25 OHD is common in patients with anorexia nervosa in the United Kingdom, 1,25(OH)2D concentrations are usually normal. Hypovitaminosis D with secondary hyperparathyroidism is relatively uncommon. The subnormal osteocalcin concentrations observed in these patients probably reflect diminished osteoblastic activity, which may contribute to their osteopenia.

Amenorrhoea, body weight and serum hormone concentrations, with particular reference to prolactin and thyroid hormones in anorexia nervosa

Twenty women with anorexia nervosa were investigated at varying stages during weight gain. Basal prolactin and TSH and prolactin responses to TRH were normal and unrelated to body weight. LH, FSH and 17 beta oestradiol were low in emaciated patients and rose with weight gain. There was no correlation between serum gonadotrophin and prolactin concentrations. T3 and T4 concentrations were low but T3 rose with weight gain during refeeding over 4-6 weeks, whereas T4 remained low. A positive correlation was found between the TSH response to TRH and body weight. The abnormalities in the hypothalamic-pituitary-thyroid axis were similar to those seen in a variety of chronic illnesses and appear to be unrelated to the amenorrhoea. The failure of restoration of normal function at least after short-term refeeding requires further investigation. It was concluded that the amenorrhoea in anorexia nervosa is not associated with changes in prolactin secretion but is determined primarily by changes in the hypothalamic-pituitary-gonadal axis. These changes are induced largely by nutritional factors but psychological factors may also be involved.

Endocrine changes and clinical profiles in depression: II. The thyrotropin-releasing hormone test

Thirty-one (43%) of 68 patients with primary depression were found to have a blunted thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH). Increased thyroid activity, as measured by the free thyroxine index (FTI), was present in 16 (24%) of the patients. Patients with blunted responses had a higher mean FTI level than those with normal responses. Patients with blunted responses were significantly more likely to exhibit the symptoms of depersonalization, derealization and agitation. There was no clear association between blunting and any particular diagnostic category of depression. Patients with blunted responses and high FTI values were more likely to report significant long-term environmental difficulties than patients with blunted responses and normal FTI values. It is suggested that there may be more than one mechanism responsible for blunting of the TSH response in depressed patients. In some patients blunting may be due to negative feedback from increased output of thyroid hormones, possibly released as part of a stress response. In other patients blunting may be due to a different mechanism, possibly involving pituitary gland dysfunction. These mechanisms would not necessarily be mutually exclusive in any one patient.

Neurobiological aspects of feeding disorders

THE purpose of this paper is to provide a selective survey of the neurobiological aspects of feeding disorders. The main focus is on anorexia nervosa as the bulk of the relevant experimental observations relate to this disorder. Furthermore consideration is given predominantly to neuroendocrine aspects as these have the greatest theoretical and practical interest. The first part of the paper deals with more general issues relating to the interaction between biological and psychological processes in anorexia nervosa. This is followed by an account of neuroendocrine and monoamine changes and their relationship to issues raised in the first section and lastly some provisional conclusions are presented.

The effects of clomiphene citrate on the hypothalamic-pituitary-gonadal axis in anorexia nervosa.

Serum luteinizing hormone (LH) responses to a course of clomiphene citrate were studied in eleven patients with anorexia nervosa at different stages of the illness. In malnourished patients basal levels of LH were invariably low. With the resumption of a normal weight a small but definite rise in LH levels was observed but this spontaneous response to weight gain was variable in that many patients continued to exhibit abnormally low LH levels. The response to clomiphene in terms of a rise in basal LH levels after administration of the drug, followed by a second peak of LH and subsequent menstrual bleeding, was clearly dependent in part on the patients nutritional state. In the malnourished state the response to clomiphene was usually either absent or incomplete. After the resumption of a more normal weight, the patients invariably showed an initial rise in LH after the clomiphene, but the second LH peak and subsequent menstruation were frequently not demonstrated. Six patients maintained a normal body weight for at least six months after a course of clomiphene, but only three of them resumed cyclical menstrual bleeding. It was concluded that factors additional to the nutritional state contribute to the prolonged amenorrhoea in anorexia nervosa and that clomiphene appears to have only a limited role in the treatment and management of patients with the disorder. Some aspects of current knowledge of the endocrine mechanisms that regulate normal menstruation and of the mode of action of clomiphene are outlined. The results of the present study are discussed against this background in an attempt to elucidate further the hypothalamic disorder underlying the amenorrhoea in anorexia nervosa.

Adrenaline-induced hyperaggregability of platelets and enhanced thromboxane release in anorexia nervosa.

Platelet aggregation and thromboxane A2 release in response to adrenaline and the relationship of this response to body weight was investigated in female patients with anorexia nervosa. Platelets obtained from patients with body weights below 75% of the expected average weight (Group I) showed significantly greater aggregation and TXA2 release in response to adrenaline when compared with controls matched for sex and age. Patients with body weights 75-95% of the expected average weight (Group II) did not show enhancement of platelet aggregation or TXA2 release. In Group I patients, platelet hyperaggregability and enhanced TXA2 release induced by adrenaline tended to normalise following inpatient treatment and weight gain: with 0.5 mumol/l adrenaline, the pre-weight gain median aggregation was 65%, whereas the post-weight gain value was 37% - P less than 0.01. Markedly underweight patients also had hyperaggregability following stimulation with ADP and collagen. This hyperaggregability also tended to normalise after weight gain but these changes were not statistically significant. Platelet hyperaggregability (especially in response to adrenaline) in anorexia nervosa is therefore secondary to weight loss and reverts to normal with normalisation of weight. These changes may reflect the previously documented increase in platelet alpha-adrenoceptors in thin patients with anorexia nervosa and their normalisation following weight gain. However, the hyperaggregability in response to agonists other than adrenaline suggests that an additional post-receptor mechanism may be involved.

Impaired colour-naming of clinically salient words as a measure of recovery in anorexia nervosa

The colour-naming performance of a group of hospitalized anorexic women (N = 12) was tested on initial admission, after 1 week of treatment and again after 12 weeks of treatment. Compared to a control population of non-clinical females (N= 18), the anorexics colour-named both food and body shape words more slowly than their neutral matched words; although colour-naming times, in general, were slower for anorexics. The size of this colour-naming impairment decreased as a function of weight gain and improvement in psychopathology, although colour-naming times for food words improved more quickly than for body shape words for both clinical and non-clinical subjects. The results of correlational analysis between colour-naming times and Eating Disorder Inventory (EDI-2) responses lead to the conclusion that colour-naming performance for body shape, rather than food words, provides a clearer index of improvement in psychopathological status in anorexia nervosa.