Miranda-Olivos, RominaBaenas, IsabelSteward, TrevorGranero, RoserPastor, AntonioSánchez, IsabelJuaneda-Seguí, AsierPino-Gutiérrez, Amparo delFernández-Formoso, José A.Vilarrasa, NuriaGuerrero-Pérez, FernandoVirgili, NúriaLópez-Urdiales, RafaelJiménez Murcia, SusanaTorre Fornell, Rafael de laSoriano Mas, CarlesFernández Aranda, Fernando2023-12-012023-12-012023Miranda-Olivos R, Baenas I, Steward T, Granero R, Pastor A, Sánchez I, et al. Exploring the influence of circulating endocannabinoids and nucleus accumbens functional connectivity on anorexia nervosa severity. Mol Psychiatry. 2023 Nov;28(11):4793-800. DOI: 10.1038/s41380-023-02253-21359-4184http://hdl.handle.net/10230/58422Anorexia 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 < 0.001) and the left supplementary motor area (NAcc-SMA; pFWE < 0.001) 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. Although no significant differences in eCBs concentrations were observed between the groups, 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 eCBs concentrations and NAcc functional connectivity in AN and HC could have clinical implications for weight maintenance, with eCBs being a potential target for AN treatment.application/pdfeng© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41380-023-02253-2NeurosciencePsychiatric disordersinfo:eu-repo/semantics/openAccess