Cingulum-Callosal white-matter microstructure associated with emotional dysregulation in children: A diffusion tensor imaging study.

Yuwen Hung,John D.E Gabrieli,Joseph Biederman,Schuyler L Gaillard,Anastasia Yendiki,Caroline Kelberman,Kelly Kadlec,Xiaoqian J Chai,Dina R Hirshfeld-Becker,Hilary Woodworth,Mathias Goncalves,James Capella,Mai Uchida,Susan Whitfield-Gabrieli,Satrajit Ghosh

doi:10.1016/j.nicl.2020.102266

Abstract

Emotional dysregulation symptoms in youth frequently predispose individuals to increased risk for mood disorders and other mental health difficulties. These symptoms are also known as a behavioral risk marker in predicting pediatric mood disorders. The underlying neural mechanism of emotional dysregulation, however, remains unclear. This study used the diffusion tensor imaging (DTI) technique to identify anatomically specific variation in white-matter microstructure that is associated with pediatric emotional dysregulation severity. Thirty-two children (mean age 9.53 years) with varying levels of emotional dysregulation symptoms were recruited by the Massachusetts General Hospital and underwent the DTI scans at Massachusetts Institute of Technology. Emotional dysregulation severity was measured by the empirically-derived Child Behavior Checklist Emotional Dysregulation Profile that includes the Attention, Aggression, and Anxiety/Depression subscales. Whole-brain voxel-wise regression tests revealed significantly increased radial diffusivity (RD) and decreased fractional anisotropy (FA) in the cingulum-callosal regions linked to greater emotional dysregulation in the children. The results suggest that microstructural differences in cingulum-callosal white-matter pathways may manifest as a neurodevelopmental vulnerability for pediatric mood disorders as implicated in the clinical phenotype of pediatric emotional dysregulation. These findings may offer clinically and biologically relevant neural targets for early identification and prevention efforts for pediatric mood disorders.

Highlights

Emotional dysregulation (ED) is a frequently encountered pediatric behavioral and emotional manifestation predictive of subsequent mood disorder
Using whole-brain diffusion weighted imaging and a dimensional framework that aligns with the NIH Research Domain Criteria (Insel et al, 2010; Versace et al, 2015), this study revealed that pediatric emotional dysregulation (ED), as a clinical dimension independent from psychiatric diagnosis, is linked to variation in white-matter microstructure within cingulum-callosal neurocircuitry
The current findings of increased emotional dysregulation severity associated with increased radial diffusivity (RD) and decreased fractional anisotropy (FA) suggest possible neural susceptibility related to axonal myelination along the cingulum and callosal pathways, which contribute to emotional dysregulation in children

Summary

Introduction

Emotional dysregulation (ED) is a frequently encountered pediatric behavioral and emotional manifestation predictive of subsequent mood disorder. It is characterized by a set of symptoms in which children fail to manage their emotions, resulting in quickness to anger, inability to refocus attention from strong emotions, and low frustration tolerance (Biederman et al, 2012a; Biederman et al, 2012b). NeuroImage: Clinical 27 (2020) 102266 regulation in youth has been found to be protective against adverse physical and mental health outcomes (Bell and McBride, 2010; National Research Council and Institute of Medicine, 2009), and longitudinal evidence has shown that ED in childhood predicts subsequent onset of mood disorders and suicidality (Biederman et al, 2009; Holtmann et al, 2011). We asked whether emotional dysregulation symptom in children can be identified by anatomically specific differences in white-matter microstructure

Results

Discussion

Conclusion