Polygenic risk for schizophrenia predicting test-measured and self-reported cognitive performance in individuals without psychosis - UTU Research Portal

A1 Refereed original research article in a scientific journal

Polygenic risk for schizophrenia predicting test-measured and self-reported cognitive performance in individuals without psychosis

Authors: Rosenqvist, Elena; Lyytikäinen, Leo-Pekka; Sormunen, Elina; Kähönen, Mika; Raitakari, Olli; Hietala, Jarmo; Pahkala, Katja; Lehtimäki, Terho; Keltikangas-Järvinen, Liisa; Rovio, Suvi; Saarinen, Aino

Publisher: BioMed Central

Publication year: 2026

Journal: BMC Psychiatry

Article number: 34

Volume: 26

eISSN: 1471-244X

DOI: https://doi.org/10.1186/s12888-026-07775-x

Publication's open availability at the time of reporting: Open Access

Publication channel's open availability : Open Access publication channel

Web address : https://doi.org/10.1186/s12888-026-07775-x

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/508602348

Self-archived copy's licence: CC BY

Self-archived copy's version: Publisher`s PDF

Abstract

Introduction

Schizophrenia is characterized by weaker test-measured cognitive performance, which is partially explained by disease-related secondary factors (after the onset of the disorder) such as side effects of antipsychotics, stigma, or sedentary behavior. We examined whether polygenic risk for schizophrenia (PRSSCZ) is associated with (a) test-measured or (b) self-reported cognitive performance in individuals who have not converted into non-affective psychosis during follow-up to extending to middle age.

Methods

The participants came from the population-based Young Finns Study, born between 1962 and 1977 (n = 2217). Participants with diagnosed non-affective psychoses were excluded from the sample. Diagnoses collected from the Care Register for Health Care. PRS_SCZ was calculated on the basis of the most recent genome-wide association study on schizophrenia. Cognitive performance was measured with (1) subtests of the Cambridge Neuropsychological Test Automated Battery, measuring visuospatial learning, reaction time, sustained attention, and executive function and (2) self-reported executive functions including distractibility, task orientation, and rigidity.

Results

In individuals who have not developed non-affective psychoses during follow-up to middle age, high PRS_SCZ was associated with lower scores in all test-measured cognitive domains. These associations sustained after controlling for health behaviors and socioeconomic factors. PRS_SCZ was not associated with self-reported distractibility or task orientation but was related to an increasing trajectory of rigidity when approaching middle age.

Conclusion

We observed lower cognitive functioning in domains similar to those reported in studies of patients with schizophrenia. Thus, some difficulties in cognitive performance may not be fully attributable to the disorder itself but may partly reflect normative developmental trajectories in individuals with high polygenic liabilities.

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Funding information in the publication:
Open Access funding provided by University of Helsinki (including Helsinki University Central Hospital). This study was financially supported by Emil Aaltonen Foundation (220255). The Young Finns Study has been financially supported by the Academy of Finland: grants 356,405, 322,098, 286,284, 134,309 (Eye), 126,925, 121,584, 124,282, 129,378 (Salve), 117,797 (Gendi), and 141,071 (Skidi); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; The Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; EU Horizon 2020 (grant 755320 for TAXINOMISIS and grant 848146 for To Aition); European Research Council (grant 742927 for MULTIEPIGEN project); Tampere University Hospital Supporting Foundation; Finnish Society of Clinical Chemistry; the Cancer Foundation Finland; pBETTER4U_EU (Preventing obesity through Biologically and bEhaviorally Tailored inTERventions for you; project number: 101080117); CVDLink (EU grant nro. 101137278) and the Jane and Aatos Erkko Foundation.