Modeling Shared and Specific Variances of Irritability, Inattention, and Hyperactivity Yields Novel Insights Into White Matter Perturbations

Cameron C McKay; Brooke Scheinberg; Ellie P Xu; Katharina Kircanski; Daniel S Pine; Melissa A Brotman; Ellen Leibenluft; Julia O Linke

doi:10.1016/j.jaac.2024.02.010

Modeling Shared and Specific Variances of Irritability, Inattention, and Hyperactivity Yields Novel Insights Into White Matter Perturbations

J Am Acad Child Adolesc Psychiatry. 2024 Mar 5:S0890-8567(24)00108-4. doi: 10.1016/j.jaac.2024.02.010. Online ahead of print.

Authors

Cameron C McKay¹, Brooke Scheinberg¹, Ellie P Xu¹, Katharina Kircanski¹, Daniel S Pine¹, Melissa A Brotman¹, Ellen Leibenluft¹, Julia O Linke²

Affiliations

¹ Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
² University of Freiburg, Freiburg, Germany. Electronic address: julia.linke@psychologie.uni-freiburg.de.

PMID: 38452811
DOI: 10.1016/j.jaac.2024.02.010

Abstract

Objective: Irritability, inattention, and hyperactivity, which are common presentations of childhood psychopathology, have been associated with perturbed white matter microstructure. However, similar tracts have been implicated across these phenotypes; such non-specificity could be rooted in their high co-occurrence. To address this problem, we use a bifactor approach parsing unique and shared components of irritability, inattention, and hyperactivity, which we then relate to white matter microstructure.

Method: We developed a bifactor model based on the Conners Comprehensive Behavioral Rating Scale in a sample of youth with no psychiatric diagnosis or a primary diagnosis of attention-deficit/hyperactivity disorder or disruptive mood dysregulation disorder (n = 521). We applied the model to an independent yet sociodemographically and clinically comparable sample (n = 152), in which we tested associations between latent variables and fractional anisotropy (FA).

Results: The bifactor model fit well (comparative fit index = 0.99; root mean square error of approximation = 0.07). The shared factor was positively associated with an independent measure of impulsivity (ρ_S = 0.88, p_FDR < .001) and negatively related to whole-brain FA (r = -0.20), as well as FA of the corticospinal tract (all p_FWE < .05). FA increased with age and deviation from this curve, indicating that altered white matter maturation was associated with the hyperactivity-specific factor (r = -0.16, p_FWE < .05). Inattention-specific and irritability-specific factors were not linked to FA.

Conclusion: Perturbed white matter microstructure may represent a shared neurobiological mechanism of irritability, inattention, and hyperactivity related to heightened impulsivity. Furthermore, hyperactivity might be uniquely associated with a delay in white matter maturation.

Keywords: aging; hyperactivity; inattention; irritability; white matter.