On the Spectrum

Chapter 7
Our finding was suggestive that young children with internalizing problems had a smaller
right amygdala volume compared to children with no problems. The results suggested a
sex-specific association between amygdala volume and internalizing problems (smaller right
and left amygdala volume in girls only). Abnormalities in the amygdala are implicated in the
pathophysiology of clinical depression and anxiety (De Bellis, Casey et al. 2000). However,
evidence regarding the amygdala volume in children with internalizing problems is conflicting.
For example, in an at-risk population, adolescent boys with a smaller right amygdala had more
depressive symptoms (Yap, Whittle et al. 2008). In contrast, van der Plas et al. showed that a
larger amygdala volume was positively correlated with fearfulness in 7-17 year old girls with
a family history of depression (van der Plas, Boes et al. 2010). A smaller amygdala volume in
girls with internalizing problems within a non-clinical population provides further evidence
for the pivotal role of the amygdala in the pathophysiology of internalizing problems. In the
present population-based sample of six-to-ten year old children, we found no relationship
between hippocampal volume and internalizing problems. The hippocampus is involved in
learning and spatial and episodic memory (Burgess, Maguire et al. 2002), and some authors
have postulated that deficits in the structure and function of the hippocampus accompany
symptoms of depression or anxiety (Videbech and Ravnkilde 2015). It is possible that the
differences in the hippocampal volume between children with and without internalizing
problems may not yet be present at a young age. Another explanation is that the structural
abnormalities in the hippocampus may only be present in individuals with severe symptoms
of depression or anxiety.
Similar to a previous report in adolescents (Vulser, Lemaitre et al. 2015), we observed
smaller global brain volumetric measures in association with internalizing problems, if analyses
were only adjusted for a child’s sex and age at scanning. However, when we additionally
controlled for various sociodemographic characteristics, there were no differences in global
brain volumetric measures between children with internalizing problems and those with no
problems. This finding confirms the notion that there are no global morphological differences
in children with internalizing problems compared to children with no problems (Price and
Drevets 2012).
However, we showed that the children with internalizing problems had thinner cortex in
several brain regions, including regions in frontal/precentral cortex and orbital cortex (shown
in Figure 1). We also observed thinner cortex in the right anterior temporal cortex in children
with internalizing problems. Existing evidence in clinical and community-based studies points
to the involvement of vmPFC and the anterior cingulate cortex in children with anxiety
and depression (Marrus, Belden et al. 2015, Vulser, Lemaitre et al. 2015). Most of these
studies were performed in adolescents, but other studies indicated that young children with
depression or subthreshold symptoms of anxiety/depression show similar cortical thinning in
right vmPFC (Ducharme, Albaugh et al. 2014, Marrus, Belden et al. 2015). Furthermore, recent
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