Structural Alterations within Cerebellar Circuitry Are Associated with General Liability for Common Mental Disorders

Accumulating mental health research encourages a shift in focus towards transdiagnostic dimensional features that are shared across categorical disorders. In support of this shift, recent studies have identified a general liability factor for psychopathology – sometimes called the ‘p factor’ – that underlies shared risk for a wide range of mental disorders. Identifying neural correlates of this general liability would substantiate its importance in characterizing the shared origins of mental disorders and help us begin to understand the mechanisms through which the ‘p factor’ contributes to risk. Here we first replicate the ‘p factor’ using cross-sectional data from a volunteer sample of 1,246 university students, and then, using high-resolution multimodal structural neuroimaging, demonstrate that individuals with higher ‘p factor’ scores show reduced structural integrity of white matter pathways, as indexed by lower fractional anisotropy values, uniquely within the pons. Whole-brain analyses further revealed that higher ‘p factor’ scores are associated with reduced gray matter volume in the occipital lobe and left cerebellar lobule VIIb, which is functionally connected with prefrontal regions supporting cognitive control. Consistent with the preponderance of cerebellar afferents within the pons, we observed a significant positive correlation between the white matter integrity of the pons and cerebellar gray matter volume associated with higher ‘p factor’ scores. The results of our analyses provide initial evidence that structural alterations in cortico-cerebellar circuitry supporting core functions related to the basic integration, coordination, and monitoring of information may contribute to a general liability for common mental disorders.