Risk for antipsychotic-induced extrapyramidal symptoms: Influence of family history and genetic susceptibility

Objectives: This study aims to further evaluate the impact of family history of primary movement disorders (FHpMD) and a candidate genetic variant on risk of antipsychotic-induced extrapyramidal symptoms (EPS). Methods: We examined 156 (76 men) inpatients receiving antipsychotics for EPS and FHpMD stratified by patient characteristics. The genetic analysis included genotyping of a multiallelic dinucleotide polymorphism in the ATP1A3 gene. Results: EPS lifetime prevalence was 69% and more frequent in the presence of FHpMD (p=0.052), particularly in patients younger than 60 years (p=0.012) and with acute dystonic reactions. The ATP1A3 polymorphism showed an allele length-dependent association with parkinsonism (p=0.019 uncorrected, p=0.057 corrected) exclusively. Carriers of the shortest allele had a 7.7-fold increased risk for parkinsonism. Conclusions: The association of FHpMD and EPS may be linked to the EPS subtype and age of the patient. A common ATP1A3 genomic variation may represent a susceptibility factor for the risk for antipsychotic-induced parkinsonism in an allele-dependent manner.