This project investigates the contribution of altered central nervous system (CNS) serotonin function to the abnormal eating patterns characteristic of bulimia nervosa. This serious psychiatric disorder leads to severe psychosocial distress and potentially serious medical consequences in approximately two percent of young women, the population at greatest risk for eating disorders. Binge eating in bulimia nervosa is thought to result in part from a deficiency in the satiety response that normally leads to meal termination. Hypo thalamic serotonin is important in meal-related satiety. Patients with bulimia nervosa have abnormalities in serotonin-mediated release of neuroendocrine hormones. The primary goal of this project is to test the hypothesis that serotonin-mediated satiety responses are abnormal in bulimia nervosa. To evaluate serotonin-mediated satiety responses, this project measures the decrease in food intake during a single-item test-meal following administration of a single oral dose of the serotonin-agonist medication m-chlorophenylpiperazine (mCPP) (0.4 mg/kg). During the three year project, serotonin-mediated satiety and neuroendocrine responses will be compared in 18 medication-free women who meet DSM-IV criteria for bulimia nervosa and 18 health female volunteers. Although dieting behaviors per se can influence serotonin function, alterations in CNS serotonin regulation in bulimia nervosa are postulated to occur independently of the effects of dieting. To test this hypothesis, this project includes a second comparison group of 18 healthy female volunteers studied while following a reduced calorie diet. This project will also assess whether stable recovery in a group of 18 women with a history of bulimia nervosa is associated with a normal pattern of decreased food intake following mCPP administration. Behavioral and neuroendocrine responses to mCPP will be evaluated using a placebo-controlled, randomized design. Subject groups will be matched for age and height-adjusted weight, with studies scheduled during the follicular phase of the menstrual cycle. Further exploratory analyses will evaluate the relationship of serotonergic responses in bulimia patients to associated psychiatric symptoms, including depressed mood and impulsive and aggressive behaviors.
