White Matter Microstructure Correlates of General and Specific Second-Order Factors of Psychopathology

Abstract

Increasing data indicate that prevalent forms of psychopathology can be organized into secondorder dimensions based on their correlations, including a general factor of psychopathology that explains the common variance among all disorders and specific second-order externalizing and internalizing factors. Despite this organization, and high levels of comorbidity between diagnoses, most existing studies on the neural correlates of psychopathology employ case-control designs that treat diagnoses as independent categories. Thus, for instance, although perturbations in white matter microstructure have been identified across a range of disorders, the majority of such studies have used case-control designs, leaving it unclear whether observed relations reflect disorder specific characteristics, or transdiagnostic patterns. Using a representative community twin sample of 410 young adults, we tested the hypothesis that some relations between white matter microstructure properties in major tracts are related to secondorder factors of psychopathology. We examined fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). White matter correlates of all second-order factors were identified after controlling for multiple tests, including the general factor (FA in the body of the corpus callosum), specific internalizing (AD in the fornix), and specific externalizing (AD in the splenium of the corpus callosum, sagittal stratum, anterior corona radiata, and internal capsule). These findings suggest that features of white matter within specific tracts are associated with broad transdiagnostic dimensions of psychopathology rather than being restricted to individual diagnostic categories.Keywords: white matter microstructure; p factor; general factor of psychopathology; bifactor model; dimensional psychopathology; second-order factors of psychopathology

Hierarchical models of psychopathology: empirical support, implications, and remaining issues

“…Replications of some findings have al­ready been published, including associations between the general factor of psychopathology and atypical white matter development 67‐69 , atypicalities in the cerebellum and its connections 70‐72 , and lack of typical segregation between the default mode and executive networks during rest 73 . Thus, we may not be far from an understanding of at least some of the neurobiological mechanisms related to the general factor of psychopathology.…”

White matter tract myelin maturation and its association with general psychopathology in adolescence and early adulthood

“…In terms of white matter integrity, commonly indexed using diffusion imaging metrics, reduced integrity in callosal (Riem et al, ) and pontine‐cerebellar (Romer et al, ) pathways are also linked to the expression of a p ‐factor. However, positive associations with corpus callosum integrity have also been observed (Hinton et al, ), hinting that neurodiversity rather than a simple deficit accompanies variation in p . Varied findings are also reported in studies of resting‐state functional connectivity, with a general psychopathology factor relating to reduced fronto‐temporal connectivity (Alnæs et al, ) as well as delayed maturation of the default mode network (DMN) (Sato et al, ), but also with increased connectivity of visual cortex with the DMN and frontoparietal networks (Elliott, Romer, Knodt, & Hariri, ).…”

Transdiagnostic neuroimaging markers of psychiatric risk: A narrative review

“…For example, the inclusion of unresolved loss or trauma as covariate in Riem et al (2019) is an important distinction from other studies, in light of substantial evidence that childhood adversity is associated with significant disturbances of white matter microstructure, particularly in the corpus callosum ( McCarthy-Jones et al, 2018 ). This could therefore account in part for the opposing findings in the corpus callosum observed in these two studies ( Hinton et al, 2019 , Riem et al, 2019 ). Furthermore, the neural correlates of general psychopathology may take a dynamic course over the lifespan, thereby affecting associations observed in different age ranges (see Table 1 ).…”

“…A large diffusion imaging study has investigated an association between the p -factor and microstructural integrity throughout the white matter skeleton in young adults ( Hinton et al, 2019 ). While controlling for specific second-order internalising and externalising factors, this study revealed a positive relationship between general psychopathology and FA in the body of the corpus callosum, indicating interhemispheric hyperconnectivity.…”

“…Unresolved-disorganised attachment, in turn controlling for general psychopathology, was uniquely associated with reduced FA in the splenium of the corpus callosum. While it is hard to reconcile these findings linking general psychopathology to callosal microstructure integrity with opposing directions of association ( Hinton et al, 2019 , Riem et al, 2019 ), they nevertheless highlight many of the difficulties inherent in comparing studies from this newly emerging literature on transdiagnostic psychopathology risk. Substantial differences in sample size, age, derivation of the general psychopathology factor, and covariates included in the analysis are likely to account for observed inconsistencies.…”