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

Psychopharmacology (Berl). 2011 Apr;214(3):729-36. doi: 10.1007/s00213-010-2079-1. Epub 2010 Nov 12.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antipsychotic Agents / adverse effects*
  • Basal Ganglia Diseases / chemically induced*
  • Basal Ganglia Diseases / epidemiology
  • Basal Ganglia Diseases / genetics*
  • Family Health*
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Mental Disorders / drug therapy
  • Mental Disorders / genetics
  • Middle Aged
  • Risk Factors
  • Sodium-Potassium-Exchanging ATPase / genetics*
  • Young Adult


  • ATP1A3 protein, human
  • Antipsychotic Agents
  • Sodium-Potassium-Exchanging ATPase