Structural atrophy of the right superior frontal gyrus in adolescents with severe irritability

Ji-Woo Seok, Sahil Bajaj, Brigette Soltis-Vaughan, Arica Lerdahl, William Garvey, Alexandra Bohn, Ryan Edwards, Christopher J Kratochvil, James Blair, Soonjo Hwang, Ji-Woo Seok, Sahil Bajaj, Brigette Soltis-Vaughan, Arica Lerdahl, William Garvey, Alexandra Bohn, Ryan Edwards, Christopher J Kratochvil, James Blair, Soonjo Hwang

Abstract

Severe irritability is common in youths with psychiatric disorders and results in significant dysfunction across domains (academic, social, and familial). Prior structural MRI studies in the pediatric population demonstrated that aberrations of cortical thickness (CT) and gray matter volume (GMV) in the fronto-striatal-temporal regions which have been associated with irritability. However, the directions of the correlations between structural alteration and irritability in the individual indices were not consistent. Thus, we aim to address this by implementing comprehensive assessments of CT, GMV, and local gyrification index (LGI) simultaneously in youths with severe levels of irritability by voxel-based morphometry and surface-based morphometry. One hundred and eight adolescents (46 youths with severe irritability and 62 healthy youths, average age = 14.08 years, standard deviation = 2.36) were scanned with a T1-weighted MRI sequence. The severity of irritability was measured using the affective reactivity index. In youths with severe irritability, there was decreased CT, GMV, and LGI in the right superior frontal gyrus (SFG) compared to healthy youths, and negative correlations between these indices of the SFG and irritability. Our findings suggest that structural deficits in the SFG, potentially related to its role in inhibitory control, may be critical for the neurobiology of irritability.

Trial registration: ClinicalTrials.gov NCT02824627.

Keywords: cortical thickness; gray matter volume; gyrification; insula; superior frontal gyrus; superior temporal gyrus.

Conflict of interest statement

None of the authors have conflict of interest to disclose.

© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.

Figures

FIGURE 1
FIGURE 1
VBM correlation analysis (p < .001, uncorrected) in the severe irritability group. Brain regions that show a negative correlation with the severeness of irritability (ARI scores). Right superior frontal gyrus (peak MNI coordinate: [39, −17, 65]); right parahippocampal gyrus (peak MNI coordinate: [−23, −5, −30]); left precentral gyrus (peak MNI coordinate: [−65, 6, 24]); left middle occipital gyrus (peak MNI coordinate: [−33, −75, 6]); right caudate (peak MNI coordinate: [20, 26, 9]); right cerebellum (peak MNI coordinate: [−2, −68, −11]). The x‐axis represents the ARI score, and the y‐axis shows the relative amount of GMV
FIGURE 2
FIGURE 2
SBM correlation analysis in the severe irritability group (p < .001, uncorrected at peak level). Clusters that had significant correlation of CT with ARI scale values. The x‐axis represents the ARI score, and the y‐axis shows the CT
FIGURE 3
FIGURE 3
Links between LGI and severity of irritability in the severe irritability group. Shown are correlations at p ≤ .001, uncorrected for multiple comparisons. The x‐axis represents the ARI score, and the y‐axis shows the LGI

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