Glucocorticoid signalling dysregulation and immune cell adaptation in Anorexia Nervosa.
TL;DR
It is shown that women with AN, at the first medical evaluation, exhibit hyperactivity and hypercortisolemia, together with a reduced immune cell count yet paradoxically showing increased levels of cell activation, suggesting that cortisol elevation and immune cell adaptation may perpetuate disease vulnerability beyond weight normalization.
Abstract
Anorexia Nervosa (AN) is a neuropsychiatric disorder marked by compulsive weight-loss and hyperactivity, with poorly understood underlying mechanisms and limited treatment outcomes. Here we show that women with AN, at the first medical evaluation, exhibit hyperactivity and hypercortisolemia, together with a reduced immune cell count yet paradoxically showing increased levels of cell activation. One year later, only subjects considered in remission showed greater increases in cortisol and cytokine levels, along with enhanced monocyte differentiation and recruitment. Using the activity-based anorexia (ABA) rat model, we reproduced AN core features, including hypercorticosteronemia, and observed innate-skewed immune profiles, as well as persistent microglial and glucocorticoid receptor (GR) dysfunction in the ventral hippocampus. Pharmacological blockade of GR with RU486 attenuated hyperactivity and reshaped microglial phenotype in the ventral hippocampus. Our results suggest that cortisol elevation and immune cell adaptation may perpetuate disease vulnerability beyond weight normalization, challenging the notion of weight regain as an indicator of remission.