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

Year: 2020

Type: article

Abstract: 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 (PRS SZ ) 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 PRS SZ and PLEs. PRS SZ was significantly associated with a latent measure of cortical thickness across the salience network (r = −0.069, p = 0.010) and PLEs showed a number of significant associations with properties of the salience and default mode networks (involving the insular cortex, supramarginal gyrus and pars orbitalis, p FDR < 0.050); with the cortical thickness of the insula largely mediating the relationship between PRS SZ and auditory hallucinations. 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 hallucinations show structural associations with PLEs in the general population.

Source: Translational Psychiatry

DOI: 10.1038/s41398-020-0794-x

Authors: C. Alloza, M. Blesa-Cábez, M. E. Bastin, J. W. Madole, C. R. Buchanan, J. Janssen, J. Gibson, I. J. Deary, E. M. Tucker-Drob, H. C. Whalley, C. Arango, A. M. McIntosh, S. R. Cox, S. M. Lawrie

Institutions: Hospital General Universitario Gregorio Marañón, Centro de Investigación Biomédica en Red de Salud Mental, Instituto de Investigación Sanitaria Gregorio Marañón, University of Edinburgh, MRC Centre for Reproductive Health, The University of Texas at Austin, Universidad Complutense de Madrid

Language: English

Topic: Schizophrenia research and treatment

Subfield: Psychiatry and Mental health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,290

Funders: Fundación Mutua Madrileña, Fundación Alicia Koplowitz, University of Texas at Austin, Ministerio de Ciencia, Innovación y Universidades, European Commission, University of Edinburgh, Centro de Investigación Biomédica en Red de Salud Mental, Centre for Cognitive Ageing and Cognitive Epidemiology, National Institutes of Health, Horizon 2020 Framework Programme, Medical Research Council, Instituto de Salud Carlos III, European Regional Development Fund, National Institute on Aging, Eunice Kennedy Shriver National Institute of Child Health and Human Development

OpenAlex ID: W3017803460