Reduced plasma orexin-A concentrations are associated with cognitive deficits in anorexia nervosa

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.We thank CERCA Programme/Generalitat de Catalunya for institutional support. This manuscript and research was supported by grants from the Ministerio de Economía y Competitividad (PSI2015-68701-R), Ministerio de Sanidad, Servicios Sociales e Igualdad (PR338/17), Instituto de Salud Carlos III (ISCIII) (FIS PI14/00290 and PI17/01167) and co-funded by FEDER funds/European Regional Development Fund (ERDF), a way to build Europe. CIBERObn and CIBERSAM are both initiatives of ISCIII. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. This research was supported by a PNSD (PR338/17-MSSSI) grant. GMB is supported by a predoctoral AGAUR grant (2018 FI_B2 00174), grant co-funded by the European Social Fund (ESF) “ESF”, investing in your future. With the support of the Secretariat for Universities and Research of the Ministry of Business and Knowledge of the Government of Catalonia. CVA is supported by a predoctoral Grant of the Ministerio de Educación, Cultura y Deporte (FPU16/01453). ABC is funded by a research contract “Miguel Servet” (CP17/00088) from the ISCIII