Anorexia nervosa (AN) is a serious psychiatric disorder resulting in psychosocial distress for patients and their families, potentially severe medical consequences, and substantial long-term mortality. Occurring most commonly in young women, the disorder is frequently refractory to currently available treatments. Moreover, weight restoration achieved during extended inpatient or outpatient treatment is often followed by recurrence of eating disorder symptoms and relapse to low weight. A major emphasis in current therapeutic research in AN is exploration of new interventions to stabilize recovery and prevent relapse in patients who have achieved weight restoration. This exploratory grant application focuses on stabilization of recovery in AN. Although the etiology of AN is unknown, altered regulation of the neurotransmitter serotonin in the central nervous system (CNS) is thought to contribute to preoccupation with body shape and weight, dysregulated eating patterns, persistent anxiety, and frequent mood fluctuations. Abnormalities in CNS serotonin regulation have also been identified in individuals who have recovered from AN, as reflected in elevated levels of the serotonin metabolite 5-HIAA in cerebrospinal fluid, alterations in serotonin receptor function in PET imaging studies, and altered behavioral responses following administration of serotonin-active drugs. This project uses a randomized, placebo-controlled, double-blind crossover design to assess the potential therapeutic effects of a mixture of branched-chain amino acids in individuals who have recovered from AN. It is hypothesized this intervention, by decreasing serotonin synthesis through lowered CNS tryptophan levels, will diminish residual eating disorder symptoms. If the behavioral outcomes are positive and the amino acid mixture is well tolerated, results of this exploratory study will provide the basis for designing a larger controlled trial to test the effectiveness of this intervention in relapse prevention in the treatment of AN. Relevance to Public Health: Anorexia nervosa is a serious disorder involving abnormal eating patterns, severe weight loss and related psychiatric and medical problems. Following recovery from anorexia nervosa, relapse to low weight is a frequent problem. This exploratory study will assess whether abnormal regulation of the naturally occurring neurochemical serotonin may contribute to this important public health problem. ? ?
