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

Abstract

Prader-Willi syndrome is a rare neurodevelopmental genetic disorder characterized by various endocrine, cognitive and behavioural problems. The symptoms include an obsession for food and reduced satiety, which leads to hyperphagia and morbid obesity. Neuropsychological studies have reported that Prader-Willi patients display altered social interactions with a specific weakness in interpreting social information and responding to them, a symptom close to that observed in autism spectrum disorders. In the present case-control study, we hypothesized that brain regions associated with compulsive eating behaviour would be abnormally activated by food-related odours in Prader-Willi syndrome, as these can stimulate the appetite and induce hunger-related behaviour. We conducted a brain imaging study using the olfactory modality because odours have a high-hedonic valence and can cause stronger emotional reactions than other modalities. Further, the olfactory system is also intimately associated with the endocrine regulation of energy balance and is the most appropriate modality for studies of Prader-Willi syndrome. A total of 16 Prader-Willi participants were recruited for this study, which is a significant achievement given the low incidence rate of this rare disease. The second group of 11 control age-matched subjects also participated in the brain imaging study. In the MRI scanner, using an MRI-compatible olfactometer during 56 block sessions, we randomly presented two odours (tulip and caramel), which have different hedonic valence and a different capacity to arouse hunger-related behaviour. Our results demonstrate that Prader-Willi participants have abnormal activity in the brain reward system that regulates eating behaviour. Indeed, we found that these patients had right amygdala activity up to five times higher in response to a food odour (caramel) compared with the tulip odour. In contrast, age-matched control participants had similar activity levels in response to both odours. The amygdala activity levels were found to be associated with the severity of the hyperphagia in Prader-Willi patients. Our results provide evidence for functional alteration of the right amygdala in Prader-Willi syndrome, which is part of the brain network involved in food addiction modulated by the ghrelin and oxytocin systems, which may drive the hyperphagia. Our study provides important new insights into the functioning of emotion-related brain circuits and pathology, and it is one of the few to explore the dysfunction of the neural circuits involved in emotion and addiction in Prader-Willi syndrome. It suggests new directions for the exploration and remediation of addictive behaviours.