The children of parents with depression are at increased risk of experiencing depression themselves and often experience the onset of illness earlier than children without a family history of depression. While depression may emerge during childhood or early adolescence in children with high familial risk, pediatric major depressive disorder is often missed and delays in recognition and treatment are common.
Mai Uchida, MD, Director of the MGH Child Depression Program, and colleagues have been studying children with familial risk for depression in an attempt to identify reliable predictors of risk for developing later major depressive disorder (MDD). Previous research has suggested that subsyndromal depressive symptoms in children may predict the subsequent onset of major depressive disorder. In a recent study children at familial risk for depression (i.e., having a parent with a lifetime diagnosis of major depression or panic disorder) were followed prospectively. Uchilda and colleagues examined whether the widely used Child Behavior Checklist (CBCL) could be used to identify the children at greatest risk of MDD. They observed that among children with a familial risk for depression, subsyndromal scores on the CBCL-Anxiety/Depression subscales were associated with greater risk for developing MDD (odds ratio, OR=6.18) within 10 years of follow-up as compared to children with no family history of depression.
In another study, Uchida and colleagues used neuroimaging to look for changes in the white matter microstructure that were associated with higher risk for MDD (as defined as increased depression and anxiety scores on the CBCL). A total of 32 children (16 boys and 16 girls aged 6-12 years) underwent MRI scanning, including T1-weighted whole-head anatomical and diffusion-weighted imaging scans.
In this study, they observed a significant negative correlation between CBCL-Anxiety/Depression scores and fractional anisotropy (FA) localized in the right anterior cingulate gyrus (CG) and connected corpus callosal (CC) region. Fractional anisotropy is a sensitive index of microscopic white matter integrity and is interpreted as a measurement of the magnitude of neural connectivity. Thus what this study suggests is that higher levels of depression and anxiety measured using the CBCL were associated with decreased white-matter connectivity in the tract with projections to the anterior cingulate gyrus.
These findings are consistent with other studies indicating that risk for depression is associated with structural variation in the anterior fronto-limbic system. These neural pathways are implicated in cognitive attribution and regulation of emotional processing, which plays a key role in emotional regulation. Uchida speculates that these changes in the CC-CG microstructure are linked to increased vulnerability to MDD and may involve impairment of cognitive-emotional regulatory mechanisms.
Many questions remain. The white matter tract differences associated with elevated CBCL Anxiety/Depression scores could reflect underlying vulnerabilities to anxiety or depression; on the other hand, they may reflect the impact of the child’s experience with subclinical or clinical anxiety or depression, or both. Regardless of whether these differences in connectivity are a cause or a consequence of anxiety and depression symptoms, the neural findings associated with elevations in Anxiety/Depression scores on the CBCL could be considered as a potential biomarker for risk of depression. Using neuroimaging to identify brain differences associated with the development of MDD, we may be able to identify children at risk for pediatric MDD and thus have an opportunity to institute interventions that prevent or mitigate the effects of depression in this population.
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Uchida M, Hung Y, Green A, Kelberman C, Capella J, Gaillard SL, Gabrieli JDE, Biederman J. Association between frontal cortico-limbic white-matter microstructure and risk for pediatric depression. Psychiatry Res Neuroimaging. 2021 Oct 16;318:111396.
