Associations Between Brain Structural Alterations, Executive Dysfunction, and General Psychopathology in a Healthy and Cross-Diagnostic Adult Patient Sample

Background A general psychopathology 'p' factor captures shared variance across mental disorders in diverse samples and may partly reflect executive dysfunction. Higher p factor scores have been related to structural alterations within the visual association cortex (VAC) and a cerebello-thalamo-cerebrocortical circuit (CTCC), both of which are important for executive control. Here, we tested replicability of these direct associations as well as the indirect role of executive functioning in a sample of healthy and cross-diagnostic adult patients.Methods We conducted hypothesis-driven (i.e., region-of-interest) and exploratory whole-brain structural neuroimaging analyses using data from the Consortium for Neuropsychiatric Phenomics study of 272 adults who met diagnostic criteria for schizophrenia, bipolar disorder, or attention deficit-hyperactivity disorder or were healthy controls. Using structural equation modeling, we examined direct and indirect relations between structural neural alterations (within regions-of-interest and regions identified from exploratory analyses) and p and executive function factors.Results Higher levels of p were associated with decreased executive functioning and VAC grey matter volume, replicating previous research. In contrast, we failed to replicate prior negative relations between the p factor and CTCC structure. A significant indirect relation between VAC grey matter volume and p via executive function also emerged. Whole-brain analyses identified additional structural alterations in supplementary motor area/cingulate cortex, anterior corona radiata, and corpus callosum genu related to the p factor.Conclusions Executive dysfunction may be one mechanism underlying relations between brain structure and general psychopathology. Replication of VAC structural alterations related to p encourages further focus on this brain structure.