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Sex-Specific Associations of Irritability With Subcortical Brain Volumes
Mariah DeSerisy1,2,3, Huiyu Yang2, Jacob W Cohen4
1Division of Child and Adolescent Psychiatry, Department of Psychiatry, Columbia University Irving Medical Center, New York, New York.
Biological Psychiatry Global Open Science
|March 25, 2026
Summary
Irritability presents differently in boys and girls, linked to distinct brain structures. Boys show associations with reward regions, while girls show links to threat regions, suggesting targeted interventions.
Area of Science:
- Neuroscience
- Psychiatry
- Developmental Psychology
Background:
- Irritability is a transdiagnostic condition causing significant impairment.
- Behavioral presentations of irritability vary by age, sex, and diagnosis.
- Subcortical structural correlates of irritability remain underexplored.
Purpose of the Study:
- To investigate how age, sex, and diagnosis modify the subcortical structural correlates of irritability.
- To explore sex-specific differences in brain structure associations with irritability.
Main Methods:
- Utilized regression models on 1792 youths from the Healthy Brain Network dataset.
- Assessed irritability using the Affective Reactivity Index.
- Extracted subcortical volumes using FreeSurfer 6.0.1.
Main Results:
- Sex significantly modified the association between irritability and subcortical volumes.
- Higher irritability in boys was linked to smaller reward-related volumes (nucleus accumbens, caudate).
- Higher irritability in girls was linked to larger threat-related volumes (amygdala).
Conclusions:
- Sex-specific subcortical correlates may underlie sex differences in irritability presentation.
- Altered brain volumes in boys (reward) and girls (threat) could be early risk markers.
- Interventions targeting threat pathways for girls and reward pathways for boys may be beneficial.
