On the Spectrum

Brain structure and internalizing problems
evidence indicates the involvement of areas in the dorsolateral prefrontal cortex (dlPFC) in the
neurobiology of depression (Pizzagalli 2011, Shad, Muddasani et al. 2012). Frontal regions are
thought to be involved in regulation of the limbic system, including the amygdala, subgenual
cingulate cortex and the insula. Similar to ours, some of the previous studies indicated the
laterality of brain correlates of anxiety and depressive symptoms, showing predominantly
differences in the right hemisphere (De Bellis, Keshavan et al. 2002). Furthermore, decreased
gray matter volume in the postcentral gyrus and cuneus has been previously reported in
children with anxiety disorders (Strawn, Hamm et al. 2015). Interestingly, considering that
the cuneus is thought to be involved in memory (Cavanna and Trimble 2006), we previously
showed impaired memory function in these children (Blanken, White et al. 2016). At the
same time, our finding is in contrast with report of structural studies in pediatric populations
with clinical diagnoses of depression or anxiety which showed thicker cortex in these patients
compared to healthy controls (De Bellis, Keshavan et al. 2002, Fallucca, MacMaster et al.
2011). A smaller study (22 adolescents with depression and 22 controls) in adolescents,
which examined the gray matter volume in the temporal lobe, showed smaller volumes of the
right middle and superior temporal gyrus and greater volume in the subgyral temporal lobe
of adolescents with depression compared to healthy controls (Shad, Muddasani et al. 2012).
Projections from superior temporal regions into the amygdala are highly involved in anxiety
disorders and structural abnormalities are reported in young patients with generalized
anxiety disorders (De Bellis, Keshavan et al. 2002). Comparisons of the previous studies with
ours should be made with caution since we examined cortical thickness (as opposed to gray
matter volume in some of the previous studies) in a non-clinical sample of young children
with internalizing problems. The overlap between areas with thinner cortex in children with
internalizing problems observed in this study and studies of older children or adolescents
with depression and anxiety indicates a continuum in cortical morphological abnormalities
related to internalizing problems into childhood and non-clinical populations.
The present study had several strengths including a large sample size and utilizing the
same scanner and protocol for all children which eliminated the possibility of bias due to
acquisition factors. To date, few studies examined brain structural abnormalities associated
with internalizing problems in non-clinical samples of young children, in particular children
younger than eight years. We adjusted the analyses for several confounders, e.g. maternal
psychopathology and child intelligence, as suggested in the literature (Connell and Goodman
2002). Nonetheless, our study faced some limitations. First, MRI scans were performed
once and on average 1.6 years after the collection of the behavioral assessment. Therefore,
no inferences can be made on the temporal direction of the association or trajectories of
development. Second, internalizing behavior was parent-rated and a clinical diagnostic workup
for depression or anxiety was not available in all these children. Third, cortical segmentation
of the anterior temporal lobe in FreeSurfer was suboptimal in the anterior temporal regions,
so the interpretation of findings in the anterior temporal should be done with caution.
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