Neural Responses to Intranasal Oxytocin in Youths With Severe Irritability

Soonjo Hwang1, Ji-Woo Suk1, Harma Meffert1

  • 1Department of Psychiatry (Hwang, Lerdahl, Edwards), Department of Psychology (Delizza), and Department of Neurological Sciences (Soltis-Vaughan, Cordts), University of Nebraska Medical Center, Omaha; Digital Health Research Division, Korea Institute of Oriental Medicine, Daejeon, South Korea (Suk); Slimmer AI, Groningen, the Netherlands (Meffert); Cognitive Ability and Plasticity Lab, University of Sheffield, Sheffield, U.K. (Garvey); Section on Mood Dysregulation and Neuroscience, NIMH, Bethesda, Md. (Leibenluft); Child and Adolescent Mental Health Center, Mental Health Services, Capital Region of Denmark, Copenhagen (Blair).

PubMed

Insights

Intranasal oxytocin reduced irritability in youths with disruptive mood and behavior disorders by altering neural responses in emotion processing areas. This suggests a potential new treatment for severe irritability.

Area of Science:

  • Neuroscience
  • Psychiatry
  • Pharmacology

Background:

  • Severe irritability in youth is linked to disruptive mood and behavior disorders (DMDD/DBDs).
  • Emotion processing deficits are implicated in these conditions.
  • Oxytocin is a neuropeptide with potential neuromodulatory effects.

Purpose of the Study:

  • To investigate the neural effects of intranasal oxytocin on emotion processing in youths with severe irritability.
  • To assess the impact of oxytocin on clinical symptoms of irritability, aggression, and overall severity.

Main Methods:

  • A randomized, placebo-controlled trial involving 52 youths with severe irritability (ARI score ≥4).
  • Participants received daily intranasal oxytocin or placebo for 3 weeks.
  • Functional MRI (fMRI) with an affective Stroop task was used to measure neural responses in 43 participants.

Main Results:

  • Oxytocin treatment significantly improved clinical ratings of irritability (CGI-S, CGI-I) compared to placebo.
  • fMRI revealed reduced blood-oxygen-level-dependent (BOLD) responses to emotional stimuli in the dorsomedial prefrontal cortex and posterior cingulate cortex after oxytocin.
  • These neural changes correlated with improvements in clinical severity.

Conclusions:

  • Intranasal oxytocin shows preliminary evidence of inducing neural changes in emotion processing in youths with severe irritability.
  • These neural-level changes may underlie the observed improvements in irritability symptoms and severity.
Abstract