Bulimia nervosa is a major psychiatric disorder characterized by recurrent episodes of binge eating, purging behaviors, and psychological symptoms including preoccupation with body shape and weight. This syndrome affects an estimated two to five percent of young women who are at highest risk for the disorder. This project examines the hypothesis that low serotonin function contributes to impaired satiety and therefore bulimic episodes. Preclinical studies have demonstrated increased meal size and body weight in response to measures decreasing serotonin activity in the medial basal hypothalamus. Descriptions of blunted post-prandial satiety, therapeutic response to antidepressant medication, and pharmacological / neuroendocrine challenge responses in bulimic patients suggest a biological vulnerability involving central serotonin pathways. Studies in human volunteers have shown that dieting behavior with reduced carbohydrate intake may lower the ratio of tryptophan (a precursor to serotonin synthesis) to other large neutral amino acids (TRP/LNAA ratio) resulting in less tryptophan available in the central nervous system. One question to be studied in this proposal is whether reduced central serotonin synthesis in bulimic patients is likely to result in part from dietary-related decreases in central tryptophan availability. A second question is whether altered central serotonin function in bulimic patients can be demonstrated using an acute """"""""pharmacological"""""""" challenge with an amino acid formula leading to decreased central serotonin synthesis. This project is comprised of three phases, each involved in the development of the applicant as a clinical nurse investigator and as an institutional and academic resource in the area of eating disorders. Phase I focuses on collaboration in an ongoing placebo-controlled pharmacological challenge with the serotonin agonist fenfluramine in bulimic patients and healthy controls. Phase II focuses on implementation of a double-blind, placebo controlled study of behavioral and metabolic responses to a low-tryptophan amino acid challenge in bulimic patients and healthy controls. Phase III will extend these results to other patients and high risk groups, and include the development of an additional challenge using a selective receptor agonist to further understand synaptic activity. This project will contribute to new data on the role of serotonin in eating disorders while establishing the role of the applicant as a clinical nurse researcher, educator, and consultant in the academic and institutional setting.
| Wolfe, B E; Metzger, E D; Levine, J M et al. (2001) Laboratory screening for electrolyte abnormalities and anemia in bulimia nervosa: a controlled study. Int J Eat Disord 30:288-93 |
| Jimerson, D C; Mantzoros, C; Wolfe, B E et al. (2000) Decreased serum leptin in bulimia nervosa. J Clin Endocrinol Metab 85:4511-4 |
| Wolfe, B E; Metzger, E D; Levine, J M et al. (2000) Serotonin function following remission from bulimia nervosa. Neuropsychopharmacology 22:257-63 |
| Metzger, E D; Levine, J M; McArdle, C R et al. (1999) Salivary gland enlargement and elevated serum amylase in bulimia nervosa. Biol Psychiatry 45:1520-2 |
| Wolfe, B E; Metzger, E; Jimerson, D C (1997) Research update on serotonin function in bulimia nervosa and anorexia nervosa. Psychopharmacol Bull 33:345-54 |
| Jimerson, D C; Wolfe, B E; Metzger, E D et al. (1997) Decreased serotonin function in bulimia nervosa. Arch Gen Psychiatry 54:529-34 |
| Jimerson, D C; Wolfe, B E; Brotman, A W et al. (1996) Medications in the treatment of eating disorders. Psychiatr Clin North Am 19:739-54 |
| Rempusheski, V F; Wolfe, B E; Dow, K H et al. (1996) Peer review by nursing research committees in hospitals. Image J Nurs Sch 28:51-3 |
| Wolfe, B E; Metzger, E D; Jimerson, D C (1995) Comparison of the effects of amino acid mixture and placebo on plasma tryptophan to large neutral amino acid ratio. Life Sci 56:1395-400 |
| Wolfe, B E (1994) The use of challenge studies in biobehavioral nursing research. Arch Psychiatr Nurs 8:145-9 |
