Neural Responses to Intranasal Oxytocin in Youths With Severe Irritability

Soonjo Hwang, Ji Woo Suk, Harma Meffert, Arica Lerdahl, William F. Garvey, Ryan Edwards, Alison Delizza, Brigette Soltis-Vaughan, Katrina Cordts, Ellen Leibenluft, R. J.R. Blair

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


OBJECTIVE: The authors investigated the neural impact of intranasal oxytocin on emotion processing areas in youths with severe irritability in the context of disruptive mood and behavior disorders. METHODS: Fifty-two participants with severe irritability, as measured by a score ≥4 on the Affective Reactivity Index (ARI), with diagnoses of disruptive behavior disorders (DBDs) and/or disruptive mood dysregulation disorder (DMDD) were randomly assigned to treatment with intranasal oxytocin or placebo daily for 3 weeks. Assessments were conducted at baseline and at the end of the trial; the primary outcomes were measures of irritability on the ARI and ratings on the Clinical Global Impressions severity scale (CGI-S) focusing on DBD and DMDD symptoms, and secondary outcomes included the CGI improvement scale (CGI-I) and ratings of proactive and reactive aggressive behavior on the Reactive-Proactive Aggression Questionnaire. Forty-three participants (22 in the oxytocin group and 21 in the placebo group) completed pre- and posttreatment functional MRI (fMRI) scans with the affective Stroop task. RESULTS: Youths who received oxytocin showed significant improvement in CGI-S and CGI-I ratings compared with those who received placebo. In the fMRI data, blood-oxygen-level-dependent (BOLD) responses to emotional stimuli in the dorsomedial prefrontal cortex and posterior cingulate cortex were significantly reduced after oxytocin compared with placebo. These BOLD response changes were correlated with improvement in clinical severity. CONCLUSIONS: This study provides initial and preliminary evidence that intranasal oxytocin may induce neural-level changes in emotion processing in youths with irritability in the context of DBDs and DMDD. This may lead to symptom and severity changes in irritability.

Original languageEnglish (US)
Pages (from-to)291-298
Number of pages8
JournalAmerican Journal of Psychiatry
Issue number4
StatePublished - Apr 1 2024


  • Disruptive Behavior Disorder
  • Disruptive, Impulse-Control, and Conduct Disorders
  • Irritability
  • Neuroimaging
  • Oxytocin
  • Psychopharmacology

ASJC Scopus subject areas

  • Psychiatry and Mental health


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