March 2025 | DOI: 10.2147/NDT.S514514
Schizophrenia polygenic scores (SCZ PRS) represent the collective influence of many genetic variants, that individually have only small effects, on a person’s risk to develop schizophrenia (SCZ). They are studied as a predictor for many traits and outcomes in mental illness. In this review, the authors examine the association of SCZ PRS with treatment outcomes across SCZ, major depressive disorder (MDD), and bipolar disorder (BD). A higher SCZ PRS has been associated with poorer treatment outcomes, including treatment resistance or non-remission to antidepressants in MDD, poorer response to antipsychotics in SCZ, and lower lithium efficacy in BD. SCZ PRS are also associated with persistent negative symptoms, cognitive impairments, and long-term illness severity in SCZ. Currently, the predictive power of SCZ PRS alone it too small to be useful in clinical care. However, combining SCZ PRS with environmental factors, other biological information, and neuroimaging data could improve prediction models. Despite some variation in findings, the overall evidence suggests that SCZ PRS has a cross-diagnostic influence on disease progression and treatment outcomes and can be one important puzzle piece in the ongoing efforts towards precision psychiatry.
