Exploring the Influence of Circulating Endocannabinoids and Nucleus Accumbens Functional Connectivity on Anorexia Nervosa Severity

Author:

Miranda-Olivos Romina,Baenas Isabel,Steward Trevor1ORCID,Granero Roser,PASTOR ANTONIORCID,Sánchez Isabel,Juaneda Asier,Pino Amparo Del,Fernández-Formoso Jose A.,Vilarrasa Nuria,Guerrero-Pérez Fernando,Virgili Nuria,López-Urdiales Rafael,Jiménez-Murcia Susana,Torre Rafael de la2ORCID,Soriano-Mas Carles3ORCID,Fernandez-Aranda Fernando4ORCID

Affiliation:

1. University of Melbourne

2. Institut Hospital del Mar d'Investigacions Mèdiques

3. IDIBELL

4. Bellvitge University Hospital-IDIBELL-University of Barcelona

Abstract

Abstract Anorexia nervosa (AN) is a severe psychiatric disorder characterized by a harmful persistence of self-imposed starvation resulting in significant weight loss. Research suggests that alterations in the nucleus accumbens (NAcc) and circulating endocannabinoids (eCBs), such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG), may contribute to increased severity and maladaptive behaviors in AN, warranting an examination of the interplay between central reward circuitry and eCBs. For this purpose, we assessed NAcc functional connectivity and circulating AEA and 2-AG concentrations in 18 individuals with AN and 18 healthy controls (HC) to test associations between circulating eCBs, NAcc functional connectivity, and AN severity, as defined by body mass index (BMI). Decreased connectivity was observed between the NAcc and the right insula (NAcc-insula; pFWE<.001) and the left supplementary motor area (NAcc-SMA; pFWE<.001) in the AN group compared to HC. Reduced NAcc-insula functional connectivity mediated the association between AEA concentrations and BMI in the AN group. However, in HC, NAcc-SMA functional connectivity had a mediating role between AEA concentrations and BMI. Our findings provide insights into how the interaction between eCBs and NAcc functional connectivity influences AN severity. Altered NAcc-insula and NAcc-SMA connectivity in AN may impair the integration of interoceptive, somatosensory, and motor planning information related to reward stimuli. Furthermore, the distinct associations between eCB levels and NAcc functional connectivity in AN and HC could have clinical implications for weight maintenance, with eCBs being a potential target for AN treatment.

Publisher

Research Square Platform LLC

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