SEROTONIN FUNCTION IN PATIENTS WITH EATING DISORDERS

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The syndrome of bulimia nervosa is a serious psychiatric disorder characterized by abnormal eating patterns with psychological symptoms involving preoccupation with body shape and weight. Bulimia nervosa is estimated to affect up to two per cent of women (and a smaller number of men) of high school and college age, the population at highest risk. Recently there has also been increased awareness of the significant prevalence of binge eating with associated psychological distress, provisionally identified as binge eating disorder, in overweight subjects who do not purge. Neurobiological alterations may contribute to the initial onset and / or to the perpetuation of symptoms in these disorders. There is much current interest in the hypothesis that impaired central serotonin function contributes to blunted post-prandial satiety responses in patients with bulimia nervosa. This hypothesis is consistent with preclinical studies demonstrating a major role for hypothalamic serotonin in mediating meal-induced satiety. Preliminary evidence for reduced serotonin function in some normal weight bulimia nervosa patients has emerged from studies of pharmacological / neuroendocrine challenge responses, cerebrospinal fluid metabolites, and pharmacological treatment studies. Utilizing single-blind, placebo-controlled acute pharmacological challenge with the serotonin agonist fenfluramine, this study will compare neuroendocrine responses in currently Symptomatic female bulimia nervosa patients at normal weight, in symptom remitted bulimia nervosa patients, in overweight patients with binge eating symptomatology, in overweight patients free of binge eating behaviors, and in age- and sex-matched controls. As a follow-up step in identifying possible mechanisms of serotonin synaptic dysregulation in bulimia nervosa, this project will also conduct double-blind, placebo-controlled pharmacological challenge studies with a selective serotonin-1A receptor agonist in female patients with bulimia nervosa and healthy controls. Clinical variables such as duration and severity of bulimic symptoms, body weight and dietary pattern, severity of depressive symptoms, and alterations in menstrual function will be evaluated as predictors of altered serotonergic responsiveness. This study will provide new data on the possible role of central serotonergic alterations in the pathophysiology of bulimia nervosa and in the provisionally identified syndrome of binge eating disorder.