The Neurobiology of emotion regulation in anorexia nervosa (NEA)

神经性厌食症 (NEA) 情绪调节的神经生物学

• 批准号: 249366886
• 负责人: Professor Dr. Timo Brockmeyer
• 金额: --
• 依托单位: Klinik für Allgemeine Innere Medizin und Psychosomatik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/249366886?language=en
• 关键词: Neurobiology; emotion; regulation; anorexia; nervosa

Anorexia nervosa (AN) is a serious mental illness featuring high morbidity and mortality. Theoretical models propose that food restriction and weight loss may attenuate the intensity in which AN patients experience negative emotions. This is considered an important maintenance factor in AN. Previous studies have shown that AN patients have great difficulties regulating negative emotions, and that they show elevated levels of emotional avoidance. Moreover, our workgroup was able to show that lower body weight in AN patients is associated with less difficulties in emotion regulation and less negative emotions in autobiographic memories. However, it remains unknown how dietary restraint and weight loss lead to attenuated negative affect. According to psychobiological models, dietary restraint may cause alterations in brain activity and serotonergic function that may underlie altered emotional processing in underweight AN patients. Food restriction, by reducing plasma tryptophan (TRP) availability and thereby brain 5-HT functional activity, may provide the AN individual with temporary respites from aversive mood states. TRP, the precursor of 5-HT, is an essential amino acid which is only available in the diet. Food intake, depending on the proportion of carbohydrate and protein, can enhance brain 5-HT release. A low-caloric diet was found to be associated with decreased plasma levels of TRP and altered 5-HT activity in healthy women. Correspondingly, AN patients exhibit low TRP plasma levels which, however, increase during weight gain. TRP depletion in healthy adults has lead to reduced startle effects, reduced recognition of and subjective emotional arousal in response to affective stimuli. In turn, experimentally induced temporary increases in TRP in healthy women lead to a significant increase of negative mood and enhanced perception of fearful stimuli. These theoretical considerations and empirical findings give rise to the hypothesis that in AN patients food restriction and weight loss may serve the avoidance of aversive emotional responses through alterations in brain activity and decreases in TRP availability, representing a psychobiological mechanism to compensate for trait-like emotion regulation deficits. However, there is a lack of empirical studies specifically examining these proposed links. Therefore, we aim at investigating whether short-term TRP increases in AN patients lead to increased responsivity of the limbic network to aversive stimuli. Furthermore, we will investigate differences in cortical down regulation of the limbic network between patients and controls. For this purpose, we will conduct a randomized, double-blind, placebo-controlled, repeated-measures, experimental fMRI design with two independent groups (AN patients, healthy controls). This may allow for a better understanding of the psychopathology of AN, thereby providing a major contribution to the refinement of existing treatment approaches.

神经性厌食症（Anorexia nervosa，AN）是一种严重的精神疾病，具有较高的发病率和死亡率。理论模型表明，食物限制和减肥可能会减弱AN患者经历负面情绪的强度。这被认为是AN中的重要维护因素。先前的研究表明，AN患者在调节负面情绪方面有很大的困难，并且他们表现出更高的情绪回避水平。此外，我们的研究表明，AN患者的体重较轻与情绪调节困难较少和自传体记忆中的负面情绪较少有关。然而，目前还不清楚饮食限制和减肥如何导致负面影响减弱。根据心理生物学模型，饮食限制可能会导致大脑活动和多巴胺能功能的改变，这可能是体重过轻的AN患者情绪处理改变的基础。食物限制，通过减少血浆色氨酸（TRP）的可用性，从而脑5-HT功能活性，可以提供AN个体与暂时喘息从厌恶情绪状态。TRP是5-HT的前体，是一种必需氨基酸，仅在饮食中可获得。食物的摄入，根据碳水化合物和蛋白质的比例，可以促进大脑5-HT的释放。低热量饮食被发现与健康女性血浆TRP水平降低和5-HT活性改变有关。相应地，AN患者表现出低TRP血浆水平，然而，其在体重增加期间增加。健康成人TRP耗竭导致惊吓效应降低，对情感刺激的识别和主观情绪唤起降低。反过来，在健康女性中，实验诱导的TRP暂时增加会导致负面情绪的显着增加和对恐惧刺激的感知增强。这些理论的考虑和实证研究结果产生的假设，在AN患者的食物限制和减肥可能有助于通过改变大脑活动和TRP可用性的减少，代表一种心理生物学机制，以弥补特质样的情绪调节缺陷，以避免厌恶的情绪反应。然而，缺乏专门研究这些拟议的联系的实证研究。因此，我们的目的是调查是否短期TRP增加AN患者导致增加的边缘系统网络的反应性厌恶刺激。此外，我们将调查患者和对照组之间的边缘网络皮质下调的差异。为此，我们将进行一项随机、双盲、安慰剂对照、重复测量的实验性fMRI设计，其中包括两个独立的组（AN患者，健康对照）。这可能有助于更好地了解AN的精神病理学，从而为现有治疗方法的改进做出重大贡献。