White matter microstructure, traumatic brain injury, and disruptive behavior disorders in girls and boys

Abstract

Introduction: Girls and boys presenting disruptive behavior disorders (DBDs) display differences in white matter microstructure (WMM) relative to typically developing (TD) sex-matched peers. Boys with DBDs are at increased risk for traumatic brain injuries (TBIs), which are also known to impact WMM. This study aimed to disentangle associations of WMM with DBDs and TBIs.

Methods: The sample included 673 children with DBDs and 836 TD children, aged 9-10, from the Adolescent Brain Cognitive Development Study. Thirteen white matter bundles previously associated with DBDs were the focus of study. Analyses were undertaken separately by sex, adjusting for callous-unemotional traits (CU), attention-deficit hyperactivity disorder (ADHD), age, pubertal stage, IQ, ethnicity, and family income.

Results: Among children without TBIs, those with DBDs showed sex-specific differences in WMM of several tracts relative to TD. Most differences were associated with ADHD, CU, or both. Greater proportions of girls and boys with DBDs than sex-matched TD children had sustained TBIs. Among girls and boys with DBDs, those who had sustained TBIs compared to those not injured, displayed WMM alterations that were robust to adjustment for all covariates. Across most DBD/TD comparisons, axonal density scores were higher among children presenting DBDs.

Discussion: In conclusion, in this community sample of children, those with DBDs were more likely to have sustained TBIs that were associated with additional, sex-specific, alterations of WMM. These additional alterations further compromise the future development of children with DBDs.

Keywords: behavior problems; diffusion MRI (dMRI); multivariate analysis; tractometry; traumatic brain injury.

Figure 1

Flowchart describing participant selection. From the full baseline sample (n = 11,875), after excluding participants with moderate or severe TBI (“mod/sev TBI”), a disruptive behavior disorders (DBD raw) and a typically developing (TD) group were created. The DBD raw group was defined as Child Behavior Checklist (CBCL) T-scores of 66 or higher on either the conduct problems (CP) or oppositional defiant problems (ODP) scales or a diagnosis of present or past Conduct Disorder (CD) or Oppositional Defiant Disorder (ODD) on the Schedule for Affective Disorders and Schizophrenia for school-age children (KSADS). The “TD” group was defined as individuals with no DBDs and no callous-unemotional traits (CU), and T scores of 50 on all CBCL scales. From the TD group, we excluded 16 participants who had missing diagnostic data, and 7 who had other diagnoses. We identified participants without CU, defined as CU Sum Scores of 0, and participants with high CU, defined as CU sum scores of 4 or more and a maximum a posteriori (MAP) CU scale score scores at or above the 90th percentile. These two groups were combined to create a DBD group with approximately half of the members with high CU, and half with no CU. Scans underwent pre-processing, processing, and post-processing, leading to the exclusion of 240 DBD participants and 248 TD participants due to missing or corrupt data files, poor image quality, and failures during image processing and post-processing. The final groups of DBD and TD participants were then divided according to history of traumatic brain injury (TBI).

Figure 2

Illustration of the investigated white matter bundles. Genu, Genu of corpus callosum; Body, Body of corpus callosum; Splenium, Splenium of corpus callosum; CG, Cingulum; ILF, Inferior Longitudinal Fasciculus; IFOF, Inferior Fronto-Occipital Fasciculus; UF, Uncinate Fasciculus; CST, Corticospinal Tract.

Figure 3

Illustration of the results from the principal components analyses. (A) Plot illustrating the loadings of each diffusion measure onto each principal component (PC). Red colors represent negative loadings, blue colors represent positive loadings. The size of the circles also illustrate the magnitude of the loadings. Bar graphs underneath illustrate the variance explained by each PC, with the variance explained by the first three PCs indicated numerically on the graphs. (B) Schematic illustration of the interpretation of the first three PCs. PC1 appears to capture measures of absolute diffusivity. The loadings in girls were multiplied by −1 to ensure consistency with the boys' loadings. PC2 appears to capture measures related to axonal density. The loadings in both boys and girls were multiplied by -1 so that increasing PC2 scores could be interpreted as increasing axonal density. PC3 appears to capture selectively the number of fiber orientations. AFDf, Apparent Fiber Density along fixels; RD, Radial diffusivity; AD, Axial diffusivity; NuFO, Number of fiber orientations; MD, Mean diffusivity; FA, Fractional Anisotropy.