- Heterozygous duplication in PRKRA identified in a patient who developed severe antipsychotic-induced extrapyramidal symptoms on olanzapine.
- Findings highlight value of individualised pharmacogenomic testing to predict neuroleptic sensitivity and guide antipsychotic selection and dosing.
- Allopurinol augmentation produced symptomatic benefit, suggesting a novel antioxidative and neuroprotective strategy for managing antipsychotic sensitivity.
Psychiatr Genet. 2026 Oct 5. doi: 10.1097/YPG.0000000000000430. Online ahead of print.
ABSTRACT
Antipsychotic-induced extrapyramidal symptoms (EPS) significantly impact patient adherence and treatment outcomes in schizophrenia. While genetic susceptibility to EPS has been recognized, rare mutations influencing dopamine regulation remain underexplored. We report a case of a 43-year-old woman with atypical psychosis who developed severe EPS following olanzapine treatment, despite its lower propensity. Genetic testing revealed a heterozygous duplication in the PRKRA gene, a key regulator of stress response pathways and movement control. This finding underscores the role of individualized pharmacogenomics in optimizing care. Additionally, allopurinol augmentation in this case suggests a novel therapeutic approach for neuroleptic sensitivity, leveraging its antioxidative and neuroprotective properties.
PMID:42831374 | DOI:10.1097/YPG.0000000000000430
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