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).
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.
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.
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