Amygdala hyperactivation relates to eating behavior: a potential indicator of food addiction in Prader-Willi syndrome

Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder involving nutritional, endocrine /metabolic, emotional and behavior dimensions. There is evidence for impaired hypothalamic development and function in PWS, involving oxytocin and ghrelin, which can account for the typical PWS phenotype. Hyperphagia with addiction-like behavior is one of the common features of PWS and is a consequence of the hypothalamic dysfunction. In this study, we hypothesized that brain regions associated with compulsive eating behavior would be abnormally activated by food-related odors in PWS, as these can stimulate the appetite and induce hunger-related behavior. MethodsWe used a classic olfactory discrimination test to verify that olfaction was normal in patients with PWS. In an fMRI scanner, we presented two odors, a tulip and a caramel odor, which have a different hedonic valence and a different capacity to arouse hunger-related behavior. ResultsThere was a five-fold higher activation in the right amygdala for the caramel odor compared with the tulip odor in patients with PWS (n=14). No such hyperactivation was found in age-matched controls (n=11). Cluster analysis of clinical hyperphagia scores in patients with PWS revealed a link with the right amygdala hyperactivation. ConclusionsOur study provides evidence for functional alteration of the right amygdala in PWS, which is part of the brain reward network involved in food addiction. This finding may relate to dysfunction of the ghrelin and oxytocin systems in PWS, as these are involved in addictive behavior, appetite, and olfactory bulb regulation.