Psychotic-like experiences, polygenic risk scores for schizophrenia and structural properties of the salience, default mode and central-executive networks in healthy participants from UK Biobank
Schizophrenia is a highly heritable disorder with considerable phenotypic heterogeneity. Hallmark psychotic symptoms can be considered as existing on a continuum from non-clinical to clinical populations. Assessing genetic risk and psychotic-like experiences (PLEs) in non-clinical populations and their associated neurobiological underpinnings can offer valuable insights into symptom-associated brain mechanisms without the potential confounds of the effects of schizophrenia and its treatment. We
... leveraged a large population-based cohort (UKBiobank) including information on PLEs, polygenic risk scores for schizophrenia (szPGRS) and multi-modal brain imaging in combination with network neuroscience. Morphometric (cortical thickness, volume) and water diffusion (fractional anisotropy) properties of the regions and pathways belonging to the salience, default-mode and central-executive networks were computed. We hypothesized that these anatomical concomitants of functional dysconnectivity would be negatively associated with szPGRS and PLEs. SzPGRS was associated with a latent measure of cortical thickness across the salience network (r = -0.069, p = 0.010) and with the right insular cortex (β = -0.046, pFDR = 0.050). Moreover, PLEs showed a number of significant positive and negative associations with morphometric properties of the salience and default mode networks (pFDR < 0.050); with the cortical thickness of the insula largely mediating the relationship between szPGRS and unusual voices. These results are consistent with the hypothesis that higher genetic liability for schizophrenia is related to subtle disruptions in brain structure and predisposes to PLEs even among healthy participants. In addition, our study suggests that networks engaged during auditory verbal hallucinations show structural associations with PLEs in the general population.