Reduced Plasma Orexin-A Concentrations are Associated with Cognitive Deficits in Anorexia Nervosa

Cristina Botella,Roser Granero,Zaida Agüera,Ana B Crujeiras,Trevor Steward,Francisco J Tinahones,Rosa Baños ,Fernando Fernández‐Aranda ,Rafael De La Torre,José M Menchón,Isabel Sánchez,Cristina Vintró-Alcáraz ,Gema Frühbeck,Sarah Sauchelli,Lourdes Garrido‐Sánchez ,Nadine Riesco,Francisco Ortega ,Felipe F Casanueva,Susana Jiménez-Múrcia ,José Manuel Fernández‐Real ,Amaia Rodrı́guez ,José Carlos Fernández‐García ,Gemma Mestre‐Bach

doi:10.1038/s41598-019-44450-6

Abstract

Orexins/hypocretins are neuropeptides implicated in numerous processes, including food intake and cognition. The role of these peptides in the psychopathology of anorexia nervosa (AN) remains poorly understood. The aim of the current study was to evaluate the associations between plasma orexin-A (OXA) concentrations and neuropsychological functioning in adult women with AN, and a matched control group. Fasting plasma OXA concentrations were taken in 51 females with AN and in 51 matched healthy controls. Set-shifting was assessed using the Wisconsin Card Sorting Test (WCST), whereas decision making was measured using the Iowa Gambling Task (IGT). The AN group exhibited lower plasma OXA levels than the HC group. Lower mean scores were obtained on the IGT in AN patients. WCST perseverative errors were significantly higher in the AN group compared to HC. In both the AN and HC group, OXA levels were negatively correlated with WCST non-perseverative errors. Reduced plasma OXA concentrations were found to be associated with set-shifting impairments in AN. Taking into consideration the function of orexins in promoting arousal and cognitive flexibility, future studies should explore whether orexin partly underpins the cognitive impairments found in AN.

Highlights

Www.nature.com/scientificreports evidence to support that alterations in reward processing in anorexia nervosa (AN) patients are underpinned by altered reactivity in striatal regions[8] and to the possibility of hypothalamic inputs being overridden by top-down emotional-cognitive control regions[9]
Orexin-A (OXA), known as hypocretin 1, is a neuropeptide synthesized in the hypothalamus that is implicated in the regulation of an array of complex behaviors, including sleep/wakefulness, reward, food intake, and cognition[13,14,15,16]
Wisconsin Card Sorting Test (WCST) perseverative errors were significantly higher in the AN group compared to healthy controls (HC)

Summary

Introduction

Www.nature.com/scientificreports evidence to support that alterations in reward processing in AN patients are underpinned by altered reactivity in striatal regions[8] and to the possibility of hypothalamic inputs being overridden by top-down emotional-cognitive control regions[9]. Innovative new lines of research suggest that increased activations in fronto-striatal circuits are strongly associated with the maintenance of restrictive eating habits in AN patients[10]. These deficits in executive functioning are thought to contribute to the severity of the disorder and hinder the effectiveness of treatment by encouraging reduced food intake, body image distortions, and rigid thinking styles[11]. Taking into consideration the aforementioned importance of cognition in treatment response, it would be of great interest to determine the associations between neurocognitive performance and OXA levels in patients with AN Such findings could shed light on the emerging role of the orexinergic system in the pathophysiology of AN30

Objectives

Results

Conclusion