Unique and Shared Brain Network Correlates of Irritably, Defiance, and CU traits in Early Adolescence.

• In Event: Heterogeneity in Externalizing Psychopathology: the Contribution of Multiple Etiological Pathways Across Childhood and Adolescence.

Abstract

Introduction: Childhood irritability (i.e., anger proneness), defiance (i.e., non-compliance), and callous-unemotional (CU) traits (i.e., low empathy and guilt) are common and comorbid symptoms of childhood externalizing psychopathology, associated with high risk for substance use, relationship difficulties, academic problems, and antisocial behavior. However, while often comorbid clinically, they exhibit diverging neural correlates. This divergence has hindered the identification of reliable neural markers that could provide insight into distinct etiological risk factors and treatment targets for irritability, defiance, and CU traits. The current study aimed to parse unique and shared associations between irritability, defiance, and CU traits and resting state functionally connectivity (RSFC) within and between three large scale brain networks: the default mode (DMN), cingulo-opercular (CON), and the salience networks (SN).
Hypotheses: We hypothesized that scores on a general externalizing psychopathology factor (i.e., representing variance shared between the symptom categories) would be associated with reduced connectivity within the DMN and SN and reduced connectivity between the DMN and CON. We hypothesized that defiance and CU traits would be uniquely associated with reduced connectivity within the DMN, while irritability would be uniquely associated with increased connectivity.
Study Population: Data were from N=10,239, 9- to 11-year-old children from the Adolescent Brain and Cognitive Development (ABCD) Study, who completed behavioral and neuroimaging assessments at the baseline and third-year follow-up assessments.
Methods: We tested the fit of a bifactor model with three specific factors (i.e., irritability, defiance, and CU traits) and one general factor (externalizing psychopathology) and established convergent validity by exploring associations between factors and risk for conduct disorder (CD) and generalized anxiety disorder (GAD). We then examined associations between specific and general factors and RSFC, focusing on connectivity within and between the DMN, CON, and SN.
Results: A bifactor model specifying one general and three specific factors showed superior fit (χ2(25)=185.53, CFI=1.00, TLI=.99). General factor scores were cross-sectionally related to a CD diagnosis (childhood-onset, β=.64, p<.001; adolescent-onset, β=.40, p<.001) and GAD diagnosis (β=.41, p<.001), while higher CU traits specific factor scores were associated with greater likelihood of having a childhood-onset CD (β=.13, p<.001) but less likelihood of GAD (β=-.07, p<.05). In contrast, defiance and irritability were associated with GAD diagnosis (defiance, β=.18, p<.01; irritability, β=.40, p<.001). Similar results were found within prospective models using diagnoses at the third-year follow-up, controlling for baseline diagnostic status. Preliminary analysis of RSFC data suggests that higher general factor scores are related to increased connectivity within the CON (β=.03, p<.05) and SN (β=.03, p<.05), while defiance (β=-.04, p<.05) and irritability (β=-.04, p<.05) are related to decreased connectivity within the DMN. Finally, the defiance factor is related to increased connectivity between the DMN and CON (β = .03, p<.05).
Conclusions: Our results suggest that differences in RSFC in large-scale brain networks may be related to externalizing psychopathology broadly, while providing new insights into the specific and overlapping associations between irritability, defiance, and CU traits and RSFC. Findings inform a new understanding of the distinct neural markers of different forms of externalizing psychopathology.

Authors

• Samantha Conte Perlstein, University of Pennsylvania
  Presenting Author

• Samuel W. Hawes

• Amy L. Byrd

• Angela R. Laird

• Rebecca Waller, University of Pennsylvania