Abstract
Transdiagnostic research has identified a general psychopathology factor—often called the ‘p’ factor—that accounts for shared variation across internalizing, externalizing, and thought disorders in diverse samples. It has been argued that the p factor may reflect dysfunctional thinking present in serious mental illness. In support of this, we previously used a theory-free, data-driven multimodal neuroimaging approach to find that higher p factor scores are associated with structural alterations within a cerebello-thalamo-cortical circuit (CTCC) and visual association cortex, both of which are important for monitoring and coordinating information processing in the service of executive control. Here we attempt to replicate these associations by conducting region-of-interest analyses using data from 875 members of the Dunedin Longitudinal Study, a five-decade study of a population-representative birth cohort, collected when they were 45 years old. We further sought to replicate a more recent report that p factor scores can be predicted by patterns of distributed cerebellar morphology as estimated through independent component analysis. We successfully replicated associations between higher p factor scores and both reduced gray matter volume of the visual association cortex and fractional anisotropy of pontine white matter pathways within the CTCC. In contrast, we failed to replicate prior associations between cerebellar structure and p factor scores. Collectively, our findings encourage further focus on the CTCC and visual association cortex as core neural substrates and potential biomarkers of general psychopathology.
Highlights
Supplementary information The online version of this article contains supplementary material, which is available to authorized users.A rapidly emerging body of research has identified a general factor that captures shared variation among multiple forms of psychopathology across diverse samples [1]
Consistent with this argument, we recently used a theory-free, data-driven approach to find that among 1246 university students higher p factor scores were associated with structural alterations in a cerebellothalamo-cortical circuit (CTCC) critical for monitoring and coordinating information processing in the service of executive control [4]
Morphological features within a cerebellar component involved in cognitive functions, as well as reduced gray matter volume (GMV) within neocerebellar lobule VI and crus I, were associated with higher general psychopathology. These neocerebellar morphological features were the most important predictors of general psychopathology as compared with 52 other brain-wide anatomical features. In addition to these structural alterations within neocerebellum and broader prefrontal CTCC, we found novel evidence for decreased GMV in the visual association cortex of individuals with higher p factor scores [4]
Summary
We found that higher p factor scores were associated with patterns of inefficient intrinsic functional connectivity between visual association cortex and networks supporting executive control and self-referential processes, which are implicated across mental disorders [20] These patterns are consistent with speculation that higher p factor scores represent the likelihood of experiencing disordered thought through a diminished capacity for basic monitoring and processing of information supported by the prefrontal CTCC and connectome-wide intrinsic functional connectivity. Such patterns of brain dysfunction may contribute to negative affect, emotion dysregulation, and inefficient information processing, all of which have been posited as potential explanations of the p factor [3]. Using data from the Dunedin Study, we further sought to replicate the independent components analysis of cerebellar morphology and general psychopathology as reported by Moberget et al [19] in their study of young community volunteers
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