On the Spectrum

Brain structure and internalizing problems
Surface-based vertex-wise cortical analyses with internalizing broadband scale score
resulted in no clusters when adjusted for a child’s sex, age, and externalizing broadband
scores. Figure 2 illustrates the results of surface-based vertex-wise cortical analyses with the
empirically defined internalizing problems class adjusted for sex, age, and dummy-coded
problem classes (children with no problems were the reference). Children with internalizing
problems had thinner cortex in several brain areas in the right hemisphere including inferior
frontal (pars orbitalis), middle frontal/precentral, occipital/cuneus, and temporal cortices
when compared to children with no problems. Further adjustment for confounders and total
brain volume did not change the results (Table 3). As children in the internalizing class have
some degree of externalizing problems, which may not fully be captured by adjusting for
the externalizing class dummy variable, we reran these analyses additionally adjusted for
CBCL/1½–5 externalizing broadband scores. As presented in Supplementary Figure 1, we
found thinner cortex in clusters which largely overlapped with those of the main analysis,
including temporal lobe and inferior frontal gyrus (pars opercularis/triangularis).
Analysis with the CBCL/1½–5 borderline cut-off (based on the Dutch norm population)
revealed no significant association with brain volumetric measures or cortical thickness.
There was no significant sex interaction (p for interaction >0.05); however stratified
analyses for sex revealed that girls with internalizing problems had smaller right and left
amygdala volumes than girls with no problems (B=-79.1, 95%CI: -162.3, 4.2, p=0.06 and B=-
66.5, 95%CI: -132.0, -1.1, p=0.05, respectively). There was no association between amygdala
volume and the internalizing class of behavior in boys.
Figure 2 Cortical thickness and Internalizing Problems at 6 years
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Internalizing problems were defined using a latent profile analysis performed on all Child Behavior
Checklist/1½–5 syndrome scales(Basten, Althoff et al. 2013)
Clusters: (1) Temporal, (2) Inferior frontal cortex (Pars Orbitalis) (3) Middle Frontal/Precentral (4)
Occipital/Cuneus (5) Anterior Temporal.
RH: Right Hemisphere
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