Heterogeneity of brain volume and psychiatric symptom patterns in youth with disruptive mood and behavior disorders

This study aimed to identify symptom-derived profiles among youth with disruptive mood and behavior disorders (DMBD) based on dimensional psychopathology and to examine whether these profiles were associated with regional gray matter volume (GMV) differences.

Magnetic resonance imaging scans were acquired from 121 youth (59 DMBD, 62 typically developing controls [TDC]). Latent profile analysis (LPA) was performed using six continuous symptom indicators: irritability, callousness, uncaring and unemotional traits, and proactive and reactive aggression. Regional gray matter volumes were compared among the identified DMBD profiles and the TD group using voxel-based morphometry.

LPA identified two symptom profiles that differed primarily in overall symptom severity: a severe profile (n = 42) and a moderate profile (n = 17). The severe profile showed higher levels of most symptom indicators, with particularly pronounced differences in aggression and callousness. Exploratory whole-brain VBM identified group effects in the bilateral anterior insula, right anterior prefrontal cortex, left posterior orbital gyrus, and right lateral orbital gyrus; however, none survived whole-brain correction for multiple comparisons. Bonferroni-corrected post hoc comparisons of extracted GMV showed lower GMV in the severe profile than in the TD group in the bilateral anterior insula and right anterior prefrontal cortex. In the orbitofrontal regions, lower GMV primarily involved the moderate profile, although the pattern differed between regions.

The identified profiles primarily reflected differences in symptom severity rather than qualitatively distinct clinical subtypes. These severity-based profiles were associated with different regional GMV patterns, although the neuroimaging findings were exploratory. The findings support further investigation of dimensional symptom-based phenotyping as an approach to characterizing clinical and neurobiological heterogeneity among youth with DMBD.