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

BACKGROUND: A general psychopathology factor (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-cerebro-cortical circuit, 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 (CNP) study of 272 adults who met diagnostic criteria for schizophrenia, bipolar disorder, or attention-deficit/hyperactivity disorder or were healthy control subjects. 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 the p factor were associated with decreased executive functioning and VAC gray matter volume, replicating previous research. In contrast, we failed to replicate previous negative relations between the p factor and cerebello-thalamo-cerebro-cortical circuit structure. A significant indirect relation between VAC gray matter volume and the p factor 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 the p factor encourages further focus on this brain structure.