The Neurobiology of emotion regulation in anorexia nervosa (NEA)

神经性厌食症（Anorexia neurovosa， AN）是一种发病率和死亡率都很高的严重精神疾病。理论模型表明，饮食限制和减肥可能会减轻AN患者经历负面情绪的强度。这被认为是an中一个重要的维护因素。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，并且他们表现出较高的情绪回避水平。此外，我们的工作组能够证明，AN患者的体重较低与情绪调节困难和自传体记忆中的负面情绪较少相关。然而，目前尚不清楚饮食限制和减肥是如何减轻负面影响的。根据心理生物学模型，饮食限制可能会导致大脑活动和血清素功能的改变，这可能是体重不足的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，从而减少大脑5-羟色胺的功能活动，可以为AN个体提供暂时的缓解厌恶情绪状态的机会。TRP是5-羟色胺的前体，是一种必需氨基酸，只能从饮食中获得。食物摄入，取决于碳水化合物和蛋白质的比例，可以促进大脑5-HT的释放。研究发现，低热量饮食与健康女性血浆TRP水平降低和5-羟色胺活性改变有关。相应的，AN患者表现出较低的血浆TRP水平，然而，随着体重增加而增加。健康成人的TRP耗竭导致惊吓效应减少，对情感刺激的识别和主观情绪唤醒减少。反过来，在健康女性中，实验诱导的短暂的TRP增加导致负面情绪的显著增加和对恐惧刺激的感知增强。这些理论考虑和实证研究结果提出了一种假设，即在AN患者中，饮食限制和体重减轻可能通过改变大脑活动和降低TRP可用性来避免厌恶情绪反应，这代表了一种心理生物学机制来补偿类似特质的情绪调节缺陷。然而，缺乏实证研究专门检查这些建议的联系。因此，我们的目的是研究AN患者短期TRP升高是否会导致边缘网络对厌恶刺激的反应性增加。此外，我们将研究患者和对照组之间皮层边缘网络下调的差异。为此，我们将进行随机、双盲、安慰剂对照、重复测量的实验fMRI设计，分为两个独立组（AN患者和健康对照组）。这可能有助于更好地理解AN的精神病理学，从而为改进现有的治疗方法做出重大贡献。

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.