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

• Published in: Journal of the American Academy of Child and Adolescent Psychiatry
• Main Authors: McKay, Cameron C., Scheinberg, Brooke, Xu, Ellie P., Kircanski, Katharina, Pine, Daniel S., Brotman, Melissa A., Leibenluft, Ellen, Linke, Julia O.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.03.2024
• Subjects: aging; hyperactivity; inattention; irritability; white matter; white matter; irritability; inattention; aging; hyperactivity
• ISSN: 0890-8567; 1527-5418
• DOI: 10.1016/j.jaac.2024.02.010

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. 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). 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 (ρS = 0.88, pFDR < .001) and negatively related to whole-brain FA (r = −0.20), as well as FA of the corticospinal tract (all pFWE < .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, pFWE < .05). Inattention-specific and irritability-specific factors were not linked to FA. 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.