Association between frontal cortico-limbic white-matter microstructure and risk for pediatric depression

Abstract

This study aimed to identify white-matter microstructural characteristics associated with risk for pediatric major depressive disorder (MDD) measured by the Child Behavior Checklist (CBCL) Anxiety/Depression scores. Children (N = 32) of both sexes, aged 6-12, underwent T1-weighted whole-head anatomical and diffusion-weighted imaging. Each participant's mean diffusion measure image was generated and thinned to create an alignment-invariant tract representation. Voxel-wise analysis on the resulting map was carried out in Track Based Spatial Statistics (TBSS) using general linear models by regressing the CBCL-Anxiety/Depression score against measures of diffusion tensor imaging (DTI). We also compared these results with prior DTI findings from the same children associated with CBCL-Emotion Dysregulation profile, an indicator for bipolar disorder. TBSS voxel-wise analysis showed a significant negative correlation between fractional anisotropy (FA) and CBCL-Anxiety/Depression scores localized in the right anterior cingulum and connected corpus callosal region. The negative FA correlations in these regions were greater in CBCL-Anxiety/ Depression scores compared to CBCL-Emotional Dysregulation scores. Reduced white-matter connectivity in the anterior cingulum and connected corpus callosal region may represent a biomarker of risk for pediatric MDD. These results may help identify brain differences associated with the development of MDD, and assist with earlier clinical identification of pediatric MDD.

Keywords: Bipolar disorder; Child behavior checklist; Diffusion tensor imaging; Emotional dysregulation; Major depressive disorder; Pediatric depression; White matter.