A large review of 102 studies looked at genetics in people with schizophrenia, mostly of European ancestry, to understand treatment-resistant forms. The research found that higher polygenic risk scores, which measure genetic burden, are linked to a greater chance of treatment resistance. Specific rare genetic variants and copy number changes were also associated with this condition.
However, common genetic variants only explained a small part of the risk for treatment resistance. The tools to predict this specific outcome are still being developed. Most genetic studies focus on schizophrenia in general, showing strong overlap between treatment-responsive and resistant forms.
Other genetic data, like gene expression and epigenetic markers, offered some insights but were often limited by the effects of medication. The main limitation is that most studies involved people of European descent, so results may not apply to other groups. Definitions of treatment resistance also varied between studies.
To improve care, researchers need more diverse groups and consistent criteria. Combining genetic, biological, and clinical information could help identify risk earlier and guide personalized treatment. This review shows associations, not cause-and-effect, and the evidence certainty is not fully measured.
