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Randomized Controlled Trial
. 2025 Jul;33(4):691-699.
doi: 10.1002/erv.3167. Epub 2025 Jan 30.

Oxytocin Amplifies Negative Response to Ambiguity in Adolescent Females With and Without Eating Disorders

Affiliations
Randomized Controlled Trial

Oxytocin Amplifies Negative Response to Ambiguity in Adolescent Females With and Without Eating Disorders

Victoria Burmester et al. Eur Eat Disord Rev. 2025 Jul.

Abstract

Objective: Eating disorders (ED) typically emerge in adolescence, a critical period for brain development and peer bonding. Interpersonal difficulties-particularly social anxiety-frequently co-occur with ED. Oxytocin is a neuropeptide that modulates social cognition and linked to prosocial effects. To date, no study has investigated oxytocin's effects on negative interpretation bias toward ambiguous information in adolescents with ED.

Methods: Forty-eight female adolescents aged 16 to 17 years with and without EDs took part in a placebo-controlled, double-blinded, randomised, crossover trial investigating the effects of 24 IU intranasal oxytocin on negative interpretations of ambiguous scenarios. Participants and controls were tested twice, approximately one week apart.

Results: Contrary to hypothesis, oxytocin increased negative interpretations overall (p = 0.019, large effect). Adolescent females with AN or BN made more negative interpretations than controls when presented with ambiguous information. There was no group effect for those who reached or did not reach threshold on an autism screen.

Conclusions: This study suggests adolescents with EDs interpret ambiguous information more negatively than controls and that oxytocin administration amplifies negative responses to ambiguity in adolescent females, including in controls. Research tools that effectively identify these biases would help to widen the scope of ED treatments for adolescents.

Keywords: anorexia nervosa; bulimia nervosa; development; neuropsychology; treatment.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Timeline of sessions in parent study. † Sham time filler: participants instructed to continue with bespoke leisure activities questionnaires whilst waiting for other players. ECR‐RS = experiences in close relationships—Relationship structures; NTS = needs threat scale (cyberball); OT = oxytocin; RCADS = revised children's anxiety and depression scales (LM = low mood; SP = social phobia); social connectedness scale; VAS = visual analogue scale. Gray shading indicates measures completed during the hypothesized window of oxytocin's effects. ECR‐RS = Experiences in Close Relationships—Relationship Structures; NTS = Needs Threat Scale; OT = oxytocin; RCADS = Revised Child Anxiety and Depression Scale (LM = Low Mood; SP = social phobia); SCS = Social Connectedness Scale; VAS = visual analogue scales.
FIGURE 2
FIGURE 2
Participant recruitment through the study. Fraudulent applications from autonomous programmes (bots) were identified using Expert Review Fraud Detection on Qualtrics.
FIGURE 3
FIGURE 3
Frequency of Negative Interpretations in Control and Eating Disorder Group after placebo and oxytocin.
FIGURE 4
FIGURE 4
Interactionist Model of Negative Effects of Intranasal Oxytocin in female adolescents. Model adapted from Bartz et al. (Bartz et al. 2011). Moderators in orange are necessary components to produce a negative social response to oxytocin. Contextual moderators can include environmental and social stimuli.

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