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. 2025 Jan;33(1):53-66.
doi: 10.1002/erv.3125. Epub 2024 Jul 20.

Circadian copeptin and oxytocin profiles in anorexia nervosa: Exploring the interplay with neurohypophysis opioid tone

Sandra Doua  1   2 , Natacha Germain  1   2   3 , Manel Merabet  1   2 , Jérôme Redouté  4 , Claire Boutet  1   5 , Fabien Schneider  1   5 , Amira Hammour  1   2   3 , Aurélia Gay  1   3   6 , Catherine Massoubre  1   3   6 , Bruno Estour  1   2   3 , Bogdan Galusca  1   2   3
Affiliations

Circadian copeptin and oxytocin profiles in anorexia nervosa: Exploring the interplay with neurohypophysis opioid tone

Sandra Doua et al. Eur Eat Disord Rev. 2025 Jan.

Abstract

Context: Neurohypophysis (NH) function in eating disorders (ED) remains poorly elucidated. Studies on vasopressin and oxytocin display inconclusive findings regarding their levels and associations with psychological complications in ED. The profile of opioid tone, a crucial NH activity regulator, is also unknown.

Objective: To characterise the circadian profile of NH hormones and NH opioid tone using positron emission tomography/MRI (PET/MRI) imaging in patients with ED compared to healthy controls.

Methods: Twelve-point plasma circadian profiles of copeptin and oxytocin, alongside nutritional and psychological scores, were assessed in age-matched female participants: 13 patients with anorexia nervosa restrictive-type (ANR), 12 patients recovered from AN (ANrec), 14 patients with bulimia nervosa and 12 controls. Neurohypophysis PET/MRI [11C] diprenorphin binding potential (BPND) was evaluated in AN, ANrec and controls.

Results: Results revealed lower copeptin circadian levels in both ANR and ANrec compared to controls, with no oxytocin differences. Bulimia nervosa exhibited elevated copeptin and low oxytocin levels. [11C] diprenorphin pituitary binding was fully localised in NH. Anorexia nervosa restrictive-type displayed lower NH [11C] diprenorphin BPND (indicating higher opioid tone) and volume than controls. In ANR, copeptin inversely correlated with osmolarity. Neurohypophysis [11C] diprenorphin BPND did not correlated with copeptin or oxytocin.

Conclusion: Copeptin demonstrated significant group differences, highlighting its potential diagnostic and prognostic value. Oxytocin levels exhibited conflicting results, questioning the reliability of peripheral blood assessment. Increased NH opioid tone in anorexia nervosa may influence the vasopressin or oxytocin release, suggesting potential therapeutic applications.

Keywords: anorexia nervosa; biological; bulimia nervosa; neuroimaging.

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Conflict of interest statement

All authors have nothing to disclose.

Figures

FIGURE 1
FIGURE 1
Delineation of posterior and anterior pituitary using FSLeyes software. The MRI masks obtained with this procedure (green – neurohypophysis (NH); blue – anterior pituitary) were used for the extraction of PET [11C] diprenorphin binding potential (BPND), MRI T1 intensity and tissue volume of these regions. PET, positron emission tomography.
FIGURE 2
FIGURE 2
Mean copeptin (a) and oxytocin (b) plasma levels in the groups of the study: the patients with restrictive type anorexia nervosa (ANR), the weight‐recovered patients with ANR (ANrec), the patients with bulimia nervosa (BN) and the control individuals (Controls). Statistics: *: p < 0.05.
FIGURE 3
FIGURE 3
Circadian copeptin (a) and oxytocin (b) plasma levels in the groups of the study: the patients with restrictive type anorexia nervosa (ANR), the weight‐recovered patients with ANR (ANrec), the patients with bulimia nervosa (BN) and the control individuals (Controls). Statistics: *: p < 0.05.
FIGURE 4
FIGURE 4
MRI analysis in the groups of the study: the patients with restrictive type anorexia nervosa (ANR), the weight‐recovered patients with ANR (ANrec), and the control individuals (Controls). (a) neurohypophysis (NH) volume, (b) Neurohypophysis MRI intensity, and (c) neurohypophysis (NH) [11C] Diprenorphin BPND. Statistics: *: p < 0.05.
FIGURE 5
FIGURE 5
Representation of [11C] Diprenorphin BPND reflecting opioid activity in posterior pituitary gland in: (a) a control participant; (b) in a patient recovered from anorexia nervosa; (c) in a patient with ongoing anorexia nervosa. For each image, [11C] Diprenorphin BPND was projected on the corresponding individual MRI sagital section. Lower [11C] Diprenorphin BPND in AN or ANrec versus Controls was intepreted as a higher endogenous opioid activity.
See this image and copyright information in PMC

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