The Neurobiology of emotion regulation in anorexia nervosa (NEA)

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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.