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.

In this article, the Psych-STRATA project is presented: a multidisciplinary initiative aimed at improving the early identification and treatment of treatment-resistant psychiatric disorders, including schizophrenia, bipolar disorder, and major depressive disorder. The project takes a comprehensive approach involving the identification of genetic and clinical biomarkers, testing early intensified pharmacological treatment in a randomized controlled trial, and developing machine learning models for personalized therapy. A shared decision-making framework, including a mental health board and digital tools is implemented, alongside patient empowerment efforts. Finally, drug repurposing and AI-driven treatment recommendations aim to advance personalized, evidence-based psychiatric care.

In this article, the authors observe that the genetic load for schizophrenia is associated with the highest clozapine dose in patients who suffer schizophrenia. It is noteworthy to mention that these researchers replicated this finding in 3 independent samples, the gold standard when it comes to validate the results of a genetic study.