Anorexia nervosa is associated with higher brain mu-opioid receptor availability

Anorexia nervosa (AN) is a severe psychiatric disorder, characterized by restricted eating, fear to gain weight, and a distorted body image. Mu-opioid receptor (MOR) functions as a part of complex opioid system and supports both homeostatic and hedonic control of eating behavior. Thirteen patients with AN and thirteen healthy controls (HC) were included in this study. We measured 1) MOR availability with [11C]carfentanil positron emission tomography (PET), 2) brain glucose uptake (BGU) with 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG) PET during hyperinsulinemic-euglycemic clamp and 3) blood-oxygen-level-dependent signal with functional magnetic resonance imaging. All subjects underwent a screening visit consisting of physical examination, anthropometric measurements, fasting blood samples, an oral glucose tolerance test, psychiatric assessment, and an inquiry regarding medical history. Body fat mass (%) was measured and M value was calculated. MOR availability from caudate and putamen was higher in patients with AN and those from nucleus accumbens (NAcc) and thalamus showed the higher trend in patients with AN. There was no area where MOR availability was lower in patients with AN. BGU was not different between AN and HC. MOR availability and BGU were negatively correlated in caudate, NAcc and thalamus and showed the trend of negative association in putamen. In conclusion, AN is associated with higher MOR availability in the brain regions implicated in reward processing, while BGU remains unaltered. Therefore, the endogenous opioid system might be one of the key components underlying AN. This better understanding of AN could support the development of new treatments for AN. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT05101538 ### Funding Statement The study was supported by National Research Foundation of Korea (KP: 2020R1F1A1054201), Sigrid Juselius Foundation (LN), Gyllenberg stifftelse (LN) and Academy of Finland (LN: 294897 and 332225). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study is a part of AVAIN project registered at ClinicalTrials.gov (Anorexia Nervosa and Its Effects on Brain Function, Body Metabolism and Their Interaction, [NCT05101538][1]). The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the Hospital District of Southwest Finland. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to corresponding authors [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT05101538&atom=%2Fmedrxiv%2Fearly%2F2024%2F03%2F27%2F2024.03.26.24304878.atom