Hyperactivity in patients with anorexia nervosa and in semistarved rats: evidence for a pivotal role of hypoleptinemia.

Patients with anorexia nervosa (AN) often show normal to elevated physical activity levels despite severe weight loss and emaciation. This is seemingly in contrast to the loss of energy and fatigue characteristic of other starvation states associated with weight loss. Despite the fact that historical accounts and clinical case studies of AN have regularly commented on the elevated activity levels, the behavior has become only recently the subject of systematic study. Because rodents and other species increase their activity upon food restriction leading to weight loss when given access to an activity wheel--a phenomenon referred to as activity-based anorexia or semi-starvation-induced hyperactivity (SIH)-it has been proposed that the hyperactivity in AN patients may reflect the mobilization of phylogenetically old pathways in individuals predisposed to AN. Exogeneous application of leptin in this animal model of AN has recently been shown to suppress completely the development of SIH. Hypoleptinemia, as a result of the food restriction, may represent the initial trigger for the increased activity levels in AN patients and in food-restricted rats. In the first and second parts of our review, we will summarize the relevant findings pertaining to hyperactivity in AN patients and in the rat model, respectively. We conclude with a synopsis and implications for future research.

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.

Family functioning in anorexia nervosa differs by subtype.

OBJECTIVE: This study investigated family functioning in adolescents with the restricting and bulimic type of anorexia nervosa (AN) and in healthy controls. METHOD: Fifty-one parents and their children (17 with AN and 34 healthy adolescents) completed the Family Assessment Measure, a self-report instrument that provides information about the functional strengths and weaknesses of the family and each family member. RESULTS: AN patients with the bulimic subtype and their mothers were significantly more likely to perceive family functioning as impaired than were healthy adolescents or restricting AN patients. Restricting AN patients and their families did not differ from healthy control families. CONCLUSION: The results suggest that the problems faced by bulimic patients color their and their parents' view of each other and the family. Symptomatic and personality differences between the subtypes of AN with better control, fewer symptoms, and denial of conflict characterizing restricting AN families may be reflected in family interaction styles.

Depression and eating disorders.

Both depressive disorders and eating disorders are multidimensional and heterogeneous disorders. This paper examines the nature of their relationship by reviewing clinical descriptive, family-genetic, treatment, and biological studies that relate to the issue. The studies confirm the prominence of depressive symptoms and depressive disorders in eating disorders. Other psychiatric syndromes which occur with less frequency, such as anxiety disorders and obsessive-compulsive disorders in anorexia nervosa, or personality disorders, anxiety disorders, and substance abuse in bulimia nervosa, also play an important role in the development and maintenance of eating disorders. Since few studies have controlled for starvation-induced physical, endocrine, or psychological changes which mimic the symptoms considered diagnostic for depression, further research will be needed. The evidence for a shared etiology is not compelling for anorexia nervosa and is at most suggestive for bulimia nervosa. Since in contemporary cases dieting-induced weight loss is the principal trigger, women with self-critical or depressive features will be disproportionately recruited into eating disorders. The model that fits the data best would accommodate a relationship between eating disorders and the full spectrum of depressive disorders from no depression to severe depression, with somewhat higher rates of depression in bulimic anorectic and bulimia nervosa patients than in restricting anorexia nervosa patients, but the model would admit a specific pathophysiology and psychopathology in each eating disorder.

Behavioral activation and lack of concern, core symptoms of anorexia nervosa?

OBJECTIVE: The core symptoms of anorexia nervosa have remained points of debate. The goal of this paper is a close study of unexpected and paradoxical symptoms in anorexia nervosa which are described in the literature but which, for the most part, have escaped the attention of investigator. METHOD: Following a brief examination of psychological influences: developmental psychodynamics issues, psychiatric comorbidity and personality features, as well as the physical consequences of starvation, all of which are considered probable contributors to the pathological process, the symptoms of denial, lack of concern, contentment, liveliness, and overactivity in anorexia nervosa are discussed. RESULTS: If these symptoms are accepted as specific for anorexia nervosa, their presence suggests that starvation might generate in individuals with a vulnerability for anorexia nervosa a condition of mental and physical activation. DISCUSSION: Areas of research to test this hypothesis, positing starvation-induced arousal or activation as a physiological dysregulation in anorexia nervosa which would powerfully support food avoidance, are discussed.

Recognizing eating disorders in women.

Anorexia nervosa (AN) and bulimia nervosa (BN) are currently classified as eating disorders. Both disorders are the product of a complex interaction between psychological and physiological processes and both show considerable comorbidity with other psychiatric disorders. Physiological and endocrine abnormalities, including primary or secondary amenorrhea and menstrual dysfunction, are common and for the most part a function of the severity of weight loss, malnutrition and/or abnormal eating habits. Therefore, assessment needs to include several steps: (1) Clinical evaluation to ascertain the diagnosis, including weight and height measurements; (2) Determination of co-existing psychiatric illnesses; and (3) Physical examination and evaluation of the physiological and endocrine status. Eating disorders interfere with reproductive function. In view of the fact that dieting has reached epidemic proportions among the young female population, and given the high association between eating disorders and endocrine abnormalities as well as menstrual disturbances, all women participating in research studies should be screened for the presence of eating disorders, disordered eating, and excessive exercise.

Individual psychopathology relative to reports of unwanted sexual experiences as predictor of a bulimic eating pattern.

OBJECTIVE: The goal of this study was to determine whether family and individual psychopathology mediate the relationship between unwanted sexual experiences and bulimic eating behavior. METHOD: Sixty-one women diagnosed with bulimia nervosa and 92 women students and university staff who had never met critia for an eating disorder completed standardized questionnaires on eating behavior, sexual abuse, individual psychopathology, and family psychopathology. RESULTS: Linear regression showed bulimic eating behavior to be significantly related to sexual abuse (beta = .40; p < .0001; R2 = 8.9%). However, multiple regression analyses with family and individual psychopathology as independent variables in addition to sexual abuse showed only individual psychopathology to predict significantly abnormal eating behavior (beta = .53, p < .0001; overall R2 = 49.6%). Specifically, depressive symptoms, suicidality, and impulsive behavior, but not substance abuse, were the components of individual psychopathology most directly associated with bulimia. DISCUSSION: The findings suggest that the primary focus in treatment should not be the traumatic events themselves, but their long-term consequences for the individual.

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.

Carbohydrate metabolism and its regulatory hormones in anorexia nervosa.

Findings of studies of carbohydrate metabolism in anorexia nervosa are reviewed. Topics covered included fasting blood sugar concentrations; serum insulin concentrations, insulin receptor binding activity, insulin sensitivity, and insulin resistance; plasma ketone bodies and free fatty acids; glucose tolerance tests; growth hormone, cortisol, intestinal hormones, and norepinephrine. Metabolic changes reported in anorexia nervosa are similar to those found in human and animal studies of states of caloric and carbohydrate restriction. Restoration of normal body weight is associated with normalization of virtually all measures. It is concluded that published studies offer no conclusive evidence for a syndrome-specific impairment in carbohydrate metabolism in anorexia nervosa.

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.

The pattern of physical symptom changes in major depressive disorder following treatment with amitriptyline or imipramine.

The study describes a sequential analysis of depression-related physical symptoms and their relationship to imipramine and amitriptyline plasma levels over 4 weeks of treatment in 79 unipolar and bipolar patients hospitalized for major depressive disorder. Insomnia diminished in all patients after 2 weeks of drug administration. After 4 weeks, the sleep of patients whose depressive disorder has significantly improved was nearly normal, whereas patients who remained depressed showed continued sleep impairment. Reductions in loss of appetite, weight and sexual interest paralleled mood improvement. Tricyclic plasma levels significantly correlated with improved sleep. The findings suggest a close link between depressed mood and physical symptoms during recovery from major depressive disorder.

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.

Identifying the specific clinical actions of amitriptyline: interrelationships of behaviour, affect and plasma levels in depression.

Despite increasing knowledge of the neurochemical bases of the action of the tricyclic drugs, little is known about the sequence of psychological effects which precede recovery in drug-responsive patients. This research was aimed at identifying the specific behavioural effects associated with the therapeutic action of amitriptyline in depression. The design involved measurement (post-hoc) of weekly changes in a severely depressed placebo-resistant group who recovered with drug treatment, compared with a group of similar patients treated for the equivalent four weeks, who showed minimal to no clinical response. The research strategy, in accordance with a dose-response paradigm, was to determine which of the early changes in emotion and behaviour found in treatment responders were systematically associated with plasma concentrations of amitriptyline or its major metabolite. Amitriptyline was found to act within seven days on the components of anxiety and on hostility in the responders, and on sleep disorder in all patients. After 12 to 14 days of treatment these effects increased, with improvements in other significant components distinguishing the responders from the non-responders. At the 12th to 14th treatment days when a steady state concentration of drug in plasma was approached, reductions in anxiety and hostility and in certain somatic components correlated significantly with plasma concentrations of amitriptyline. Implications of the findings for clarifying the specificity of clinical actions of the tricyclic drugs, and for understanding the psychobiological dynamics underlying rapid drug-induced recovery in depression, were explored.

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.

'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.