Association of polygenic risk scores for schizophrenia with psychosis-proneness indicators in the general population: a narrative review

Abstract

BACKGROUND: Schizotypy (ST) and psychotic-like experiences and negative symptoms (PENS) are commonly used phenotypes in high-risk and early intervention research for schizophrenia and other non-affective psychoses. However, the origin of these phenotypes in the general population is poorly understood and their association with the genetic predisposition to psychoses has not yet been proven.

AIM: The aim of this study is to answer the question of whether data on the relations of ST and PENS with polygenic risk scores for schizophrenia (SZ-PRS) support the hypothesis that these phenotypes are subclinical manifestations of genetic liability for schizophrenia.

METHODS: Literature describing these relations in the general population was analyzed. The literature search was performed in the PubMed database using the following keywords in English: ((“schizotyp*” OR “psychotic-like experiences” OR “psychosis proneness” OR “psychotic experiences”) AND (”polygenic risk” OR “genetic liability” OR “polygenic score”)); the search in eLIBRARY.RU was conducted using the Russian words for “schizotypy”, “schizotypal features”, “psychotic experiences”, “psychotic experience”, “psychotic symptoms”, and “polygenic risk”, covering publications from 2009 to 2024.

RESULTS: Of the identified records, 45 publications were found eligible. No expected positive correlations of SZ-PRS with common ST measures have been observed. For PENS, the results are inconsistent. Overall, SZ-PRS correlate more often with the PENS general factor and negative symptoms than with psychotic experiences per se.

CONCLUSION: The literature does not provide convincing evidence of the association between SZ-PRS and ST/PENS. The search for the substantive psychological meaning of polygenic vulnerability to psychosis captured by SZ-PRS should be expanded to other personality processes and traits.

Keywords

schizophrenia / schizotypy / psychotic-like experiences / PLEs / PENS / polygenic risk scores

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Funding

Ministry of Science and Higher Education of the Russian FederationМинистерство науки и высшего образования Российской Федерации(075-15-2025-474)

RIGHTS & PERMISSIONS

Alfimova M.V.