Exploring the influence of circulating endocannabinoids and nucleus accumbens functional connectivity on anorexia nervosa severity.

Romina Miranda-Olivos, Isabel Baenas, Trevor Steward, Roser Granero, Antoni Pastor, Isabel Sánchez, Asier Juaneda-Seguí, Amparo Del Pino-Gutiérrez, José A Fernández-Formoso, Nuria Vilarrasa, Fernando Guerrero-Pérez, Nuria Virgili, Rafael López-Urdiales, Susana Jiménez-Murcia, Rafael de la Torre, Carles Soriano-Mas, Fernando Fernández-Aranda

Journal: Molecular psychiatry 2024;28(11):4793-4800

PMID: 37759041

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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; p < 0.001) and the left supplementary motor area (NAcc-SMA; p < 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.

Address: Clinical Psychology Unit, Bellvitge University Hospital, L'Hospitalet de Llobregat, 08907, Barcelona, Spain.; Ciber Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, 08907, Barcelona, Spain.; Psychoneurobiology of Eating and Addictive Behaviors Research Group, Neurosciences Program, Bellvitge Biomedical Research Institute (IDIBELL), 08908, Barcelona, Spain.; Doctoral Program in Medicine and Translational Research, University of Barcelona, 08036, Barcelona, Spain.; Melbourne School of Psychological Sciences, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, 3010, Australia.; Ciber Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, 08907, Barcelona, Spain.; Psychoneurobiology of Eating and Addictive Behaviors Research Group, Neurosciences Program, Bellvitge Biomedical Research Institute (IDIBELL), 08908, Barcelona, Spain.; Department of Psychobiology and Methodology, Autonomous University of Barcelona, 08193, Barcelona, Spain.; Ciber Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, 08907, Barcelona, Spain.; Integrative Pharmacology and Systems Neuroscience research group, Hospital del Mar Research Institute (IMIM), 08003, Barcelona, Spain.; Clinical Psychology Unit, Bellvitge University Hospital, L'Hospitalet de Llobregat, 08907, Barcelona, Spain.; Ciber Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, 08907, Barcelona, Spain.; Psychoneurobiology of Eating and Addictive Behaviors Research Group, Neurosciences Program, Bellvitge Biomedical Research Institute (IDIBELL), 08908, Barcelona, Spain.; Doctoral Program in Medicine and Translational Research, University of Barcelona, 08036, Barcelona, Spain.; Ciber de Salud Mental (CIBERSAM), Instituto Salud Carlos III, 28029, Barcelona, Spain.; Department of Psychiatry, Bellvitge University Hospital-IDIBELL, C/Feixa Llarga s/n, 08907, Barcelona, Spain.; Ciber Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, 08907, Barcelona, Spain.; Psychoneurobiology of Eating and Addictive Behaviors Research Group, Neurosciences Program, Bellvitge Biomedical Research Institute (IDIBELL), 08908, Barcelona, Spain.; Department of Public Health, Mental Health and Perinatal Nursing, School of Nursing, University of Barcelona, 08907, Barcelona, Spain.; Ciber Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, 08907, Barcelona, Spain.; Department of Endocrinology and Nutrition, Bellvitge University Hospital-IDIBELL, C/Feixa Llarga s/n, 08907, Barcelona, Spain.; CIBERDEM-CIBER de Diabetes y Enfermedades Metabólicas Asociadas, Instituto de Salud Carlos III, C/Monforte de Lemos 3-5, 28029, Madrid, Spain.; Department of Endocrinology and Nutrition, Bellvitge University Hospital-IDIBELL, C/Feixa Llarga s/n, 08907, Barcelona, Spain.; Clinical Psychology Unit, Bellvitge University Hospital, L'Hospitalet de Llobregat, 08907, Barcelona, Spain.; Ciber Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, 08907, Barcelona, Spain.; Psychoneurobiology of Eating and Addictive Behaviors Research Group, Neurosciences Program, Bellvitge Biomedical Research Institute (IDIBELL), 08908, Barcelona, Spain.; Department of Clinical Sciences, School of Medicine and Health Sciences, University of Barcelona, 08907, Barcelona, Spain.; Ciber Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, 08907, Barcelona, Spain.; Integrative Pharmacology and Systems Neuroscience research group, Hospital del Mar Research Institute (IMIM), 08003, Barcelona, Spain.; Department of Experimental and Health Sciences, Pompeu Fabra University (CEXS-UPF), 08002, Barcelona, Spain.; Ciber de Salud Mental (CIBERSAM), Instituto Salud Carlos III, 28029, Barcelona, Spain. [email protected].; Department of Psychiatry, Bellvitge University Hospital-IDIBELL, C/Feixa Llarga s/n, 08907, Barcelona, Spain. [email protected].; Department of Social Psychology and Quantitative Psychology, School of Psychology, University of Barcelona, 08035, Barcelona, Spain. [email protected].; Clinical Psychology Unit, Bellvitge University Hospital, L'Hospitalet de Llobregat, 08907, Barcelona, Spain. [email protected].; Ciber Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, 08907, Barcelona, Spain. [email protected].; Psychoneurobiology of Eating and Addictive Behaviors Research Group, Neurosciences Program, Bellvitge Biomedical Research Institute (IDIBELL), 08908, Barcelona, Spain. [email protected].; Department of Clinical Sciences, School of Medicine and Health Sciences, University of Barcelona, 08907, Barcelona, Spain. [email protected].

DOI: 10.1038/s41380-023-02253-2

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https://doi.org/10.1038/s41380-023-02253-2

MeSH Terms: Humans, Nucleus Accumbens, Anorexia Nervosa, Endocannabinoids, Magnetic Resonance Imaging, Reward