Symptoms, Serotonin and Amino Acids in Anorexia Nervosa

项目概述：神经性厌食症（AN）是一种严重的精神疾病，会给患者及其家人带来心理社会困扰，潜在的严重医疗后果，以及大量的长期死亡率。这种疾病最常见于年轻女性，目前可用的治疗方法往往难以治愈。此外，在长期住院或门诊治疗期间体重恢复后，经常会出现饮食失调症状的复发和低体重的复发。目前AN治疗研究的一个主要重点是探索新的干预措施，以稳定恢复并防止体重恢复的患者复发。这项探索性拨款申请的重点是稳定AN的恢复。虽然AN的病因尚不清楚，但中枢神经系统（CNS）中神经递质5 -羟色胺的调节改变被认为是导致对体型和体重的关注、饮食模式失调、持续焦虑和频繁情绪波动的原因。中枢神经系统5-羟色胺调节异常也已在AN恢复的个体中被发现，反映在脑脊液中5-羟色胺代谢物5-HIAA水平升高，PET成像研究中5-羟色胺受体功能改变，以及服用5-羟色胺活性药物后行为反应的改变。本项目采用随机、安慰剂对照、双盲交叉设计来评估支链氨基酸混合物对AN康复个体的潜在治疗效果。假设这种干预，通过降低中枢神经系统色氨酸水平来减少血清素合成，将减少残余的饮食失调症状。如果行为结果是积极的，并且氨基酸混合物耐受性良好，则本探索性研究的结果将为设计更大的对照试验提供基础，以测试该干预措施在AN治疗中预防复发的有效性。与公共卫生相关：神经性厌食症是一种严重的疾病，涉及异常的饮食模式、严重的体重减轻以及相关的精神和医学问题。神经性厌食症恢复后，复发到低体重是一个常见的问题。这项探索性研究将评估自然产生的神经化学物质血清素的异常调节是否可能导致这一重要的公共卫生问题。

DESCRIPTION (provided by applicant): Project Summary: 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.