Bulimia. Its incidence and clinical importance in patients with anorexia nervosa.

Among the various eating patterns encountered in anorexia nervosa, the occurrence of bulimia (rapid consumption of large amounts of food in a short period of time) is a perplexing phenomenon, because its presence contradicts the common belief that patients with anorexia nervosa are always firm in their abstinence from food. We studied the eating habits of 105 hospitalized female patients within the context of a prospective treatment study on anorexia nervosa: 53% had achieved weight loss by consistently fasting, whereas 47% periodically resorted to bulimia. The two groups were contrasted with regard to their developmental and psychosocial history, clinical characteristics, and psychiatric symptomatology. Fasting patients were more introverted, more often denied hunger, and displayed little overt psychic distress. In contrast, bulimic patients were more extroverted, admitted more frequently to a strong appetite and tended to be older. Vomiting was frequent, and kleptomania almost exclusively present in bulimic patients, who manifested greater anxiety, depression, guilt, interpersonal sensitivity, and had more somatic complaints. This association of bulimia with certain personality features and a distinct psychiatric symptomatology suggests that patients with bulimia form a subgroup among patients with anorexia nervosa.

Somatic symptoms in primary affective disorder. Presence and relationship to the classification of depression.

The incidence and severity of somatic symptoms were determined in 132 patients with major depressive disorder and 80 normal controls. The role of somatic symptoms was analyzed in relation to the unipolar-bipolar division, Research Diagnostic Criteria (RDC) subtypes, hypersomnia, and appetite increase. The data suggest that the rate and level of somatic symptoms increased with the severity of depression and age, only appetite loss differentiated unipolar from bipolar patients, and the classic somatic symptoms of depression were present in most RDC subtypes and not exclusively associated with the "endogenous" subtype. Hypersomnia or increased appetite identified two overlapping depressive subgroups; patients in both groups were young and characterized by high interpersonal sensitivity. Hypersomniac depressed patients were less anxious and agitated; patients with increased appetite were more hostile and showed a greater decrease in libido than age-matched and sex-matched patients with neither symptom.

Alterations in serum cortisol and its binding characteristics in anorexia nervosa.

The binding capacity and apparent binding affinity of corticosteroid-binding globulin (CBG) for cortisol was studied in 20 women hospitalized for anorexia nervosa. The binding capacity for cortisol, as determined kinetically at 0 C by the method of Scatchard, was similar in anorectic patients and control subjects, with mean values of 26.9 and 21.9 microgram/100 ml, respectively. The mean apparent affinity constant of CBG for cortisol was found to be significantly (P less than 0.01) lower (14.1 X 10(8) M-1) than that in control subjects (22.3 X 10(8) M-1) and was similar in blood drawn at 0830 and 2000 h. Mean morning total serum cortisol concentrations were higher in anorectic women (23.3 microgram/100 ml) than in controls (10.0 microgram/100 ml; P less than 0.001) and frequently exceeded the binding capacity of CBG. Diurnal variation was present. Mean serum 17 beta-estradiol levels were low (40.0 pg/ml) and serum progesterone was essentially absent, but mean serum testosterone levels were within the normal range. Eight patients who were retested after weight gain, when they were between 76--100% of ideal body weight, exhibited no significant changes in serum steroids or in the binding capacity or apparent affinity of CBG for cortisol.

No gender differences in placebo responses of patients with major depressive disorder.

BACKGROUND: This study was designed to compare placebo responses in men and women. METHODS: Data for 501 women and 375 men with major depressive disorder treated with placebo from seven investigational randomized double-blind trials comparing fluoxetine with placebo were analyzed. Changes in major depressive disorder symptoms with placebo administration were measured as changes in total Hamilton Depression Rating Scale scores and adverse (nocebo) effects were measured by comparing treatment-emergent signs and symptoms. RESULTS: Both women and men with major depressive disorder showed significant symptomatic improvement following placebo administration, similar in magnitude and time course of response. Women on placebo reported slightly more nocebo effects than men. CONCLUSIONS: The finding that women and men with major depressive disorder demonstrated a similar therapeutic outcome after placebo administration suggests that gender is not a predictor of placebo response.

Hormone and metabolite plasma levels after oral glucose in bulimia and healthy controls.

Bulimia patients claim to crave sweets and since as clinical evidence suggests that the food consumed during eating binges often contains large amounts of carbohydrates, hormones involved in carbohydrate metabolism might be affected in bulimia. We therefore performed a 4-hr glucose tolerance test (GTT), using 100 g oral glucose and inquired about attitudes toward sweets. Thirteen female patients, with a mean age of 23.3 years, who had had bulimia from 3 to 7 years but whose binge-eating/vomiting behavior was largely controlled at the time of testing, were compared to 14 age-matched healthy female controls with a mean age of 24.4 years. All bulimic patients and most controls had liked sweets as children and still liked sweets. Significantly more bulimic patients than controls stated they overate on sweets and avoided sweets. Glucose utilization and the insulin, glucagon, growth hormone (GH), and pancreatic polypeptide (PP) response curves in the bulimic patients were within the normal range. Fasting plasma levels of glucose, insulin, glucagon, GH, cortisol, free fatty acids (FFA), and PP were not different from controls. There was a trend in bulimic patients to have lower plasma FFA levels and higher plasma cortisol levels during the GTT than controls. The findings suggest that, given body weight maintenance and adequate nutrition, patients with bulimia nervosa have normal glucose tolerance and normal hormonal responses following an oral glucose load.

On the course of anorexia nervosa.

The authors trace three phases in the course of anorexia nervosa and compare its physical and psychological symptoms with those of starvation. Phase I, which may occur months or years before the illness, usually includes precipitating events that result in loss of self-esteem and increased self-consciousness about physical appearance. During phase II patients develop the "anorectic attitude," an unreasonable fear of eating, and show pride in their ability to lose weight. By phase III patients are forced by the severity of starvation symptoms to admit that they are ill. Although many of the physical symptoms of starvation and anorexia nervosa are similar, anorectic patients, in contrast to victims of starvation, show high initiative, the ability to suppress hunger, restless hyperactivity, and body image distortion.

Biogenic amine and metabolite levels in depressed patients with high versus normal hypothalamic-pituitary-adrenocortical activity.

The activity of the hypothalamic-pituitary-adrenocortical (HPA) axis is often high in depressive illness. The authors studied 132 depressed patients and 80 healthy control subjects. They report a significant direct association between HPA axis activity and adrenomedullary epinephrine secretion in depressed patients. They also found that depressed patients with high HPA activity tend to have lower CSF levels of 5-hydroxyindoleacetic acid, a serotonin metabolite, and modestly lower levels of 3-methoxy-4-hydroxyphenylglycol, a metabolite of epinephrine and norepinephrine, than patients with normal HPA activity. These findings provide potentially important leads for understanding interactions of biogenic amine systems with HPA axis function.

An evaluation of trace metals, vitamins, and taste function in anorexia nervosa.

Trace metals, vitamins, and other biochemical parameters were measured in 30 female patients hospitalized for anorexia nervosa with the aim of relating them to taste function, biochemical changes, and clinical signs found in this illness. Plasma zinc (71.9 +/- 14 microgram/100 ml; P < 0.01), urinary zinc (129.5 +/- 121 microgram/24 hr), and copper (84 +/- 17 microgram/100 ml; P < 0.001), were depressed, whereas zinc and copper content of hair was normal. Anorexia nervosa patients showed hypogeusia, with the bitter and sour taste most severely affected, however plasma zinc levels did not correlate with taste recognition scores. Patients showed hypercarotenemia (214 +/- 129 microgram/100 ml; P < 0.01) with normal plasma vitamin A and retinol-binding protein levels. Total iron binding capacity was depressed (261 +/- 62 microgram/100 ml; P < 0.001) in contrast to plasma iron, ceruloplasmin and folic acid, which were normal. In nine patients, who were retested before discharge, taste function improved; plasma zinc, copper, and total iron binding capacity levels increased whereas plasma carotene and cholesterol decreased to normal levels. It is concluded that the observed zinc, copper, and iron binding protein deficiencies, and hypogeusia, reflect the self-imposed nutritional restriction of anorexia nervosa patients. Zinc and other micronutrients released from catabolized tissue along with vitamin intake may mitigate against more severe deficiency states in anorexia nervosa.

Total daily energy expenditure and activity level in anorexia nervosa.

Clinical reports consistently comment on high physical activity for anorexia nervosa patients but provide few quantitative measurements. To assess activity, total daily energy expenditure (TDEE) by doubly labeled water, basal metabolic rate (BMR), and thermic effect of meals (TEM) were measured in six female outpatients with anorexia nervosa (67% of ideal body weight) and age-, sex-, and height-matched to six control subjects. Anorexia nervosa patients expended more energy as physical activity than did control subjects [0.084 +/- 0.012 vs 0.044 +/- 0.008 MJ/kg body wt, respectively (20.1 +/- 3.0 vs 10.5 +/- 1.9 kcal/kg body wt, respectively), P less than 0.04], although they had a lower BMR [4.17 +/- 0.37 vs 5.52 +/- 0.15 MJ/d, respectively (997 +/- 89 vs 1319 +/- 37 kcal/d, respectively), P less than 0.01]. TDEE and TEM were similar in both groups. There was a reduction in serum triiodothyronine (T3; 1.20 +/- 0.15 vs 2.04 +/- 0.13 nmol/L, respectively; P less than 0.003) and a slight reduction in serum thyroxine (T4); reverse T3, thyrotropin, free T4, serum cortisol, and adrenocorticotropin values were normal. BMR correlated with total body weight and fat-free mass. These results provide quantitative evidence for increased physical activity in anorexia nervosa despite profound underweight and hypometabolism.

Weight and dieting concerns in adolescents, fashion or symptom?

Attitudes toward body weight and dieting and the relations of these attitudes to psychological adjustment were investigated in 497 randomly selected adolescents who were in their senior year in one urban and two suburban midwestern high schools. Most students reported feeling physically healthy. Two thirds of female adolescents were preoccupied with weight and dieting compared with only a small number (approximately 15%) of male adolescents. Black female adolescents were found to be less weight- and diet-conscious than white female adolescents. Increased weight and dieting concerns were associated with greater body and self-image dissatisfaction, with a depressed mood, and greater overall symptomatic distress in both male and female adolescents. The fairly common fear of being overweight and thoughts about dieting experienced by contemporary female adolescents, in part, seem to reflect the greater aesthetic value that contemporary society places on thinness for women. Overall, the findings suggest that preoccupation with weight and/or dieting concerns in either male or female adolescents are likely to indicate psychological problems.

Nutrition and its relationship to aging.

The aging process alone has no significant adverse consequences for the caloric intake and the nutritional status of healthy elderly individuals. Epidemiological data suggest that in humans, in contrast to rodents, undernutrition reduces the life span. In the Western World, malnutrition in old age has become uncommon and is, for the most part, the result of physical illness and/or of psychological and socio-economic factors, such as depressive disorders, social isolation, smoking, alcohol abuse, and poverty. Body weight shows a U- or J-shaped relationship to mortality risk with the highest survival rates found at normal to moderate overweight. However, studies that have controlled for disease already present, smoking status, serum cholesterol level, or hypertension, suggest an increased mortality risk for lower and upper extremes of body weight, only. Populations with healthy lifestyles have significantly greater life expectancy that the average normal population. Even in the very old, exercise has been shown to improve muscle strength and function. The studies suggest that nutritional intake and nutritional status in old age is multifactorial and dependent not only on appetite and availability of diverse food, but also on physical activity, body mass, education, and an involved social lifestyle.

Delayed TSH release in anorexia nervosa following injection of thyrotropin-releasing hormone (TRH).

We studied plasma concentrations of thyrotropin (TSH), prolactin and growth hormone (GH) after injection of 500 microgram of thyrotropin-releasing hormone (TRH) in 10 patients with acute anorexia nervosa, subsequent to initial nutritional stabilization and again after weight recovery. Plasma thyroxine levels were normal throughout, whereas plasma triiodothyronine levels were low initially but rose with weight gain. The TSH secretory response to TRH was delayed and prolonged during the initial study but showed a normal overall quantitative response, except for two patients who showed no TSH rise. Following weight gain the TSH response was more rapid, and positive correlations were found between body weight and peak TSH levels and rapidity of TSH response. Six of 10 patients, however, continued to exhibit a delayed TSH peak response, the average response was markedly increased in comparison with that in normal females. The prolactin response curves were normal at both times. Rises in GH following TRH were observed in two patients prior to and in one patient after weight gain. We conclude that acute anorexia nervosa, with its concomitant profound weight loss, is accompanied by abnormalities in the hypothalamo-pituitary-thyroid axis, which are reversed only in part with improvement in the illness and weight gain, suggesting the persistence of disordered neuroendocrine function in this illness.

Hyperprolactinemia in two patients with eating disorders.

Two eating disorder patients with hyperprolactinemia, attributed in the first to a prolactin-secreting pituitary macroadenoma and in the second to a microprolactinoma, are described. The findings suggest that prolactin level measurements may be indicated in eating disorder patients who have a history of atypical symptoms and/or menstrual disturbances that are unrelated to weight loss.

Clonidine induced hyperphagia and weight gain in monkeys.

The effect of the alpha-noradrenergic receptor agonist, clonidine, on food intake and weight was examined in ten adult Stumptail macaque monkeys. An intramuscular injection of 0.1 mg/kg of clonidine HCl for seven consecutive days significantly increased food intake from baseline levels throughout treatment. All but two monkeys gained weight during clonidine treatment with seven animals gaining from 5--15% of their original body weight by the end of 1 week.

Clonidine-induced hyperphagia in monkeys: evidence for alpha 2-noradrenergic receptor mediation.

The mechanism of clonidine-induced hyperphagia and weight gain in monkeys was studied in 11 Stumptail macaques. Clonidine induced a significant increase in food intake over baseline levels and a significant weight gain after the 3-day treatment period. Both changes induced by clonidine were antagonized by the alpha 2-noradrenergic antagonist yohimbine, but not by prazosin, an alpha 1-noradrenergic antagonist. These results suggest that clonidine-induced hyperphagia and weight gain in monkeys are mediated through alpha 2-noradrenergic receptors.

Plasma levels of fluphenazine during fluphenazine decanoate treatment in schizophrenia.

The authors measured plasma fluphenazine levels in 20 schizophrenic patients receiving 25 or 50 mg fluphenazine decanoate (FPZ-D) by IM injection every 2 weeks. The plasma levels were determined by a sensitive gas-liquid chromatographic (GLC) assay with a nitrogen detector device developed in their laboratory. Using this chemical assay method, they replicated the finding of a sharp initial plasma peak within 24 h after the injection followed by a low but rather stable plasma level as previously reported by nonchemical assay methods. The interval plasma levels (averages of day 4-10 after injection) ranged from 0.17-0.61 ng/ml in 10 patients who received 25 mg; and 0.20-0.93 ng/ml in 7 patients who received 50 mg FPZ-D every 2 weeks. This four-fold variation in plasma levels during FPZ-D injection was smaller than previously reported levels achieved with oral antipsychotic drug treatment. Based on the study of plasma levels achieved with FPZ-D injection and oral FPZ-H (fluphenazine HC1) in 6 patients, the dosage requirement of FPZ-D appeared to be difficult to predict from the oral dosage of FPZ-H in the same patient. Two weeks past injection, fluphenazine was undetectable in approximately half the samples with the GLC method. Thus, radioimmunoassay or radioreceptor assay, which also measures metabolites, might be more suitable for the study of plasma levels in patients receiving FPZ-D injection.

Gender differences, but no racial group differences, in self-reported psychiatric symptoms in adolescents.

OBJECTIVE: To study gender differences in psychiatric symptoms and their relationship to minor delinquent behavior in high school seniors. METHOD: This was a cross-sectional study of symptoms experienced during the past 2 weeks and the past year. Male (n = 249) and female (n = 248) high school seniors attending an inner-city and two suburban high schools rated themselves on a 46-item Hopkins Symptom Checklist and a 19-item Delinquency questionnaire. RESULTS: Female adolescents, regardless of race, reported significantly higher levels of emotional distress, in particular depressed mood and anxiety, than did male adolescents. A separate factor analysis of male and female students generated anger-tension, school problems, and sadness-irritation, lethargy, respectively, as the first two factors. Trouble paying attention in school and marijuana, alcohol, and other drug use were associated with significantly higher levels of psychiatric symptoms. Black and white adolescents were similar in psychological adjustment. CONCLUSIONS: This survey confirms sex differences in the level of psychiatric symptoms for 16- to 18-year-old adolescents, suggests gender-related qualitative differences in negative emotions, and emphasizes the importance of controlling for education when studying adolescents from different ethnic or racial backgrounds.

Personality dimensions in eating disorders and their relevance for subtyping.

Personality dimensions and psychopathological symptoms were assessed in 50 female patients hospitalized for the treatment of anorexia nervosa or bulimia nervosa and in 19 healthy female controls of similar age. Restricting anorexia nervosa patients, who had lost weight by consistently reducing their food intake, reported significantly greater self-control, inhibition of emotionality, and conscientiousness than controls or bulimia nervosa patients, before and after the data were corrected for depressive and eating pathology. Both nonbulimic and bulimic anorexia nervosa patients expressed stronger than normal conformance to moral and family values. On the impulsivity dimension, bulimia nervosa patients scored in the high normal range, whereas bulimic anorexia nervosa patients rated in the low normal range. The results suggest that a personality disposition toward overcontrol and reserve might constitute a risk factor for the restricting type of anorexia nervosa through fostering restrictive behavior toward food and avoidance of personal relationships.

'La douce indifférence' and mood in anorexia nervosa: neuropsychological correlates.

1. Denial of illness, mood, eating attitudes, and the responses to visual-constructive tasks were assessed in eight right-handed female patients with restricting anorexia nervosa during the acute phase and following weight gain. 2. A lower body weight and more pronounced anorectic symptomatology were associated with increased left hemispheric activation. 3. Weight gain, greater awareness of negative affect, and overestimation of body parts were correlated with an increase in right hemispheric activation. 4. The results suggest a relationship between anorectic symptomatology and asymmetric brain activation.

Lithium transport in red cells of patients with affective disorders.

Variation in red cell Li+ transport as mediated by the Li+-Na+ exchange pathway (Li+-Na+ counterflow) appears to cause wide variation between psychiatric patients in the Li+ ratio (erythrocyte/plasma) in vivo during Li+ treatment. We obtained significant correlations between Li+ ratios determined in vivo and several measures of Li+ transport as mediated by Li+-Na+ exchange. Patients with bipolar illness had significantly lower rates of Li+ transport as mediated by this pathway than did normal subjects.