Anorexia nervosa is associated with increased mu-opioid receptor availability in brain regions involved in reward processing, such as the caudate, putamen, nucleus accumbens, and thalamus, while brain glucose uptake remains unchanged. This alteration in the endogenous opioid system may influence the perception of and response to food rewards, highlighting its central role in the neurobiology of anorexia.
Eating disorders are serious, life-threatening psychiatric conditions marked by severe disturbances in a person’s eating behaviors.
Although many people may worry about their health, weight, or appearance from time to time, some become fixated or obsessed with weight loss, body weight or shape, and controlling their food intake. These may be signs of an eating disorder.
In addition, people with eating disorders are at increased risk for medical complications and co-occurring mental illnesses, including depression, anxiety, and substance use disorders.
These co-occurring conditions may worsen eating disorders. Early detection and treatment are important for a full recovery.
Eating disorders affect millions of people worldwide. They include a wide range of disordered eating behaviors, with anorexia nervosa (AN) being one of the most concerning and life-threatening.
Anorexia nervosa is characterized by extreme restriction of food intake, an intense fear of gaining weight, and a distorted perception of one’s own body.
Despite its severity and devastating physical and psychological consequences, the brain mechanisms underlying this disorder are still not fully understood, making it difficult to develop effective treatments.
This study, conducted by researchers at Pusan National University, Korea, investigated how the brain’s opioid system, particularly the mu-opioid receptor (MOR), is involved in anorexia nervosa.
The opioid system plays a crucial role in controlling eating behavior, both in regulating basic appetite (homeostatic control) and in seeking pleasure associated with food (hedonic control).
To understand this link, the researchers analyzed 13 patients with anorexia nervosa and 13 healthy control subjects. They used different brain imaging methods, such as positron emission tomography (PET) and functional magnetic resonance imaging, to measure:
The availability of ROM in different areas of the brain.
Brain glucose uptake (BGU), an indicator of metabolic activity in the brain.
Brain signals related to blood oxygen levels, which reflect the functional activity of the brain.
In addition, all participants underwent physical examinations, psychiatric evaluations, measurements of body composition (such as fat percentage) and glucose tests, to ensure that the data obtained were accurate and contextualized.
Organization of the human opioid system in the brain. Note that since the specific projections of opioid neurons cannot be established, the figure characterizes the relative expression of different receptor subtypes at some of the key nodes of the emotion circuit. Image: Lauri Nummenmaa. DOI: 10.31234/osf.io/5w63q
The results revealed that mu-opioid receptor availability was higher in certain brain regions of patients with anorexia nervosa compared to the healthy group.
Specifically, brain regions called the caudate, putamen, nucleus accumbens (NAcc), and thalamus showed higher MOR availability in patients with anorexia nervosa.
These areas are known for their role in reward processing and motivation, suggesting that changes in the opioid system may influence how these individuals perceive and respond to food rewards.
Interestingly, no differences in brain glucose uptake (BGU) were observed between the two groups, indicating that the overall metabolic activity of the brain does not appear to be affected by anorexia nervosa.
However, a negative correlation was found between MOR availability and brain glucose uptake in some areas, such as the caudate, nucleus accumbens and thalamus, which may mean that changes in the opioid system affect how the brain uses energy in these regions.
These findings suggest that the endogenous opioid system, which regulates feelings of pleasure and reward, plays a central role in anorexia nervosa. In healthy individuals, this system helps balance appetite and motivation to eat, but in patients with anorexia nervosa, it appears to be hyperactivated in specific regions of the brain.
This change may explain why these patients have a different and often conflictual relationship with food and other forms of reward.
Better understanding the brain mechanisms of anorexia nervosa, such as changes in the opioid system, could pave the way for the development of new treatments. Currently, therapeutic options for anorexia nervosa are limited and often ineffective in the long term.
Strategies targeting the opioid system, such as medications that modulate mu-opioid receptor activity, may offer new hope for patients struggling with this devastating disorder.
This study highlights the importance of continuing to explore the neurobiology of anorexia nervosa to identify interventions that can restore balance to brain function and improve the quality of life of these individuals.
READ MORE:
Anorexia nervosa is associated with higher brain mu-opioid receptor availability.
Kyoungjune Pak, Jouni Tuisku, Henry K. Karlsson, Jussi Hirvonen, Eleni Rebelos, Laura Pekkarinen, Lihua Sun, Aino Latva-Rasku, Semi Helin, Johan Rajander, Max Karukivi, Pirjo Nuutila & Lauri Nummenmaa
Mol Psychiatry (2025).
Abstract:
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.
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