Background: A significant number of patients with schizophrenia fail to respond to antipsychotic medication. Although several studies have investigated associated patient characteristics, the emerging findings from genetic studies offer further scope for study.
Method: In 612 schizophrenia patients with detailed clinical information, common genetic variants indexed by polygenic risk scores, and rare variants indexed by deletion and duplication burden genomewide, we explored potential genetic predictors alongside other established risk factors for treatment resistance. Clinical outcomes of treatment resistance were also calculated using lifetime measures of positive, negative/disorganized and mood symptoms as well as number of hospitalizations and suicide attempts.
Results: Logistic regression models identified a significant relationship between treatment resistance and total duplication burden genomewide, years of formal schooling and age at onset. Clinically, treatment-resistant patients were characterized by greater negative/disorganized and positive symptoms and greater number of hospitalizations.
Conclusions: Taken together, these findings suggest genetic information, specifically the genomewide burden of rare copy number variants, may increase our understanding and clinical management of patients with treatment-resistant schizophrenia.
Keywords: Age at onset; clozapine; copy number variants; mutations; predictive models.