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EP991 - ECE_1551 - Reduced empathy and impaired emotion recognition in patients with arginine vasopressin deficiency

Liv-Helen Lang, Sara-Jessica Camerin, Michelle Müller, Andi Nikaj, M. Liechti, Cihan Atila, Mirjam Christ-Crain

European Journal of Endocrinology August 1, 2026 DOI: 10.1093/ejendo/lvag096.1269 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Double-blind, placebo-controlled, crossover study Peer reviewed
Sample size 30
Population Patients with arginine vasopressin (AVP) deficiency and healthy controls matched on age, sex, BMI, and menopause/hormonal contraceptive use
Interventions MDMA placebo
Dose 100 mg
Duration Single dose with a two-week wash-out period
Measures Facial Emotion Recognition Task, Multifaceted Empathy Test
Key points Patients with AVP deficiency showed lower direct empathy and reduced facial emotion recognition accuracy than controls, particularly for positive emotions, sadness, and fear. MDMA increased oxytocin about fivefold in controls but not in patients, and decreased empathy for positive emotions in patients while increasing it in controls, which the authors suggest may reflect an altered response linked to oxytocin deficiency.

Abstract

Patients with arginine vasopressin (AVP) deficiency (formerly central diabetes insipidus) often report social and emotional deficits and heightened anxiety. Growing evidence suggests that these symptoms may, at least partly, reflect concomitant OXT deficiency. OXT plays a key role in increasing empathy and improving emotion recognition. This analysis aimed to examine empathy and emotion recognition in patients with AVP deficiency compared to controls, and to assess the effects of MDMA (3,4-methylenedioxymethamphetamine), a pharmacological stimulus of OXT, on these measures. Analysis of a double-blind, placebo-controlled, crossover study including patients with AVP deficiency and healthy controls matched according to age, sex, BMI, and menopause/hormonal contraceptives. Participants received a single oral dose of MDMA (100mg) and placebo in random order, with a wash-out period of two weeks. A computer-based Facial Emotion Recognition Task and a Multifaceted Empathy Test were conducted 150 min after drug intake. The statistical analyses were performed using linear mixed-effects models. Fifteen patients and 15 controls were included (median age 34 [IQR, 25-46] vs 35 [26-48] years; 53% female). Under placebo, OXT levels were comparable between patients and controls (62 pg/mL [55-70] vs 66 pg/mL [56-74]). Following MDMA, OXT increased approximately fivefold in controls but remained unchanged in patients (92 pg/mL [79-110] vs 540 pg/mL [273-844]). Under placebo, direct empathy was lower in patients than controls (median 5.28 vs 5.62), driven by reduced empathy for positive emotions (4.50 vs 5.25). Under MDMA, direct empathy remained lower in patients (4.53 vs 5.58), with MDMA decreasing empathy for positive emotions in patients (3.55) but increasing it in controls (5.85). Linear mixed-effects modeling demonstrated significant effects mainly on the empathy dimension (P < .001) and emotional valence (P = .006), as well as a significant group × emotional valence interaction (P < .001). In emotion recognition, patients showed overall reduced accuracy compared with controls across both placebo and MDMA (P = .012), most pronounced for sadness and fear. Mixed-effects analysis confirmed significant effects of facial emotion (P < .001) without a significant group × emotion interaction, indicating a global reduction in facial emotion recognition accuracy in patients. Patients with AVP deficiency exhibit reduced empathy and impaired emotion recognition compared to controls. MDMA amplified these deficits, suggesting an altered response likely linked to OXT deficiency.