In pursuit of biomarkers for predicting susceptibility to activity-based anorexia (ABA) in adolescent female rats

Abstract

Anorexia nervosa (AN) has high rates of mortality and low rates of recovery, with outcomes that worsen with illness duration. Improved early intervention strategies are required and identifying risk factors that contribute to the development of AN is critical to their implementation. The development of AN often follows a pre-existing diagnosis of anxiety disorders and obsessive-compulsive disorder and substantial genetic overlap between these conditions suggest common underlying features may predict vulnerability to AN. Moreover, patients with AN have increased levels of circulating proinflammatory cytokines, which may be involved in susceptibility to pathological weight loss considering that children with immune dysfunction have a higher risk of subsequent AN diagnoses. Here, we used the activity-based anorexia (ABA) model to examine whether baseline levels of locomotion, anxiety-like behaviour, compulsive behaviour, and circulating immune markers predict the subsequent development of pathological weight loss in adolescent female rats. While none of these primary features were shown to differentiate rats that went on to be susceptible or resistant to weight loss in ABA, increased locomotion and anxiety-like behaviour were both associated with the extent of weight loss in susceptible but not resistant animals. Intriguingly, behaviour related to poor decision-making in a situation of conflict was shown to predict vulnerability to ABA. Future research using the ABA model to uncover early predictors of AN should focus on translationally relevant assays of decision-making and cognitive behaviour, dysfunction of which may not only predispose animals to ABA but may also represent an endophenotype linking anorectic, anxiety-like and compulsive behaviour.