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

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. PRSSCZ 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 PRSSCZ was associated with lower scores in all test-measured cognitive domains. These associations sustained after controlling for health behaviors and socioeconomic factors. PRSSCZ 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. Clinical trial number Not applicable.