Structural Neurodevelopmental Correlates of Temperamental Irritability and Externalizing Symptomology

• In Event: 3-140 - Neural Correlates of Behavior Disorders in Early Childhood: Evidence From Multiple Neuroimaging Methods

Integrative Statement

Introduction: Children high in temperamental irritability are at increased risk for developing depression, anxiety, and/or demonstrate disruptive behavior later in life (Nigg, 2006; Rothbart & Posner, 2006; Stringaris and Goodman, 2009). There is evidence that temperamental irritability influences the development of emotional processing in children, reflected in caudate and putamen activation (Karim & Perlman, 2017). Similarly, clinically irritable 6-10 year old children have aberrant putamen and pallidum activation during frustration (Perlman et al., 2015) suggesting a relationship between the activity of these basal ganglia structures and irritability in childhood that spans the normal:abnormal divide. The relationship between these structures and irritability during this important time for foundation brain development is still not well-understood. This study aims to elucidate the relationship between temperamental variations in children, basal ganglia volume, and clinical symptoms in children.

Methods: Temperament for 122 children ages 4 to 12 years old were assessed using the parent-reported Child Behavior Questionnaire (CBQ; 13 scales). To characterize groups based on temperament profiles, exploratory factor loadings were assessed followed by k-means clustering on the first principle components. To quantify basal ganglia structure, children underwent structural MR scanning. Volumes were extracted from usable scans (n=110) for the following basal ganglia structures: caudate, putamen, pallidum, and nucleus accumbens. Volumes were corrected for age, estimated intracranial volume, and sex by regressing those variables out and performing analyses on the residualized data. Finally, total externalizing and internalizing symptomology was derived from the parent-reported Child Behavior Checklist (CBCL). Using multivariate analyses of variance (MANOVA), relations among temperament group, basal ganglia structure, and symptomology were examined.

Results: Children clustered best when split in 2 groups (silhouette score=0.31): temperamentally irritable (n=58; high in CBQ anger/frustration, activity, discomfort, and sadness) and temperamentally well-regulated (n=62; high in CBQ attention focusing, soothability, and inhibitory control). The irritable group had larger pallidum (p=0.017) volumes on average than the well-regulated group, and larger pallidum volumes were associated with higher externalizing scores (p=0.017). Additionally, the irritable group had increased symptomology for both externalizing and internalizing (ps<0.001). There was no significant group*externalizing interaction predicting pallidum volumes (p>0.1).

Conclusion: The pallidum emerged as the structure most predicted by both temperament group and externalizing symptomology. These results provide evidence for a distinct but inter-related relationship between temperament and symptomology influencing neurodevelopment. Future directions include probing group by age associations as well as group differences in thickness of cortical regions known to regulate the basal ganglia.

Authors

• M. Catalina Camacho, University of Pittsburgh
  Presenting Author

• Alex Burlew, University of Pittsburgh
  Non-Presenting Author

• Susan Perlman, University of Pittsburgh
  Non-Presenting Author