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

Meike Kasten1, Norbert Brüggemann, Inke R König

  • 1Department of Psychiatry and Psychotherapy, University of Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.

Psychopharmacology
|November 13, 2010
PubMed
Abstract

Insights

Family history of primary movement disorders (FHpMD) increases the risk of antipsychotic-induced extrapyramidal symptoms (EPS), especially in younger patients. A specific ATP1A3 gene variation is linked to increased parkinsonism risk.

Area of Science:

  • Neuroscience
  • Genetics
  • Pharmacology

Background:

  • Antipsychotic medications are crucial for treating psychiatric disorders but can induce extrapyramidal symptoms (EPS).
  • Family history of primary movement disorders (FHpMD) is a potential risk factor for developing EPS.
  • Genetic factors may influence individual susceptibility to antipsychotic side effects.

Purpose of the Study:

  • To investigate the combined impact of FHpMD and a specific genetic variant (ATP1A3) on the risk of antipsychotic-induced EPS.
  • To identify patient characteristics that modify the association between FHpMD and EPS.
  • To explore the role of ATP1A3 gene polymorphism in antipsychotic-induced parkinsonism.

Main Methods:

  • A cohort of 156 inpatients receiving antipsychotics was analyzed.
  • Patients were stratified based on FHpMD and the presence of EPS.
  • Genetic analysis involved genotyping of a dinucleotide polymorphism in the ATP1A3 gene.

Main Results:

  • EPS had a 69% lifetime prevalence and was more common with FHpMD (p=0.052), particularly in patients under 60 (p=0.012) and those experiencing acute dystonic reactions.
  • The ATP1A3 polymorphism showed an allele length-dependent association with parkinsonism (p=0.019 uncorrected, p=0.057 corrected).
  • Carriers of the shortest ATP1A3 allele had a 7.7-fold increased risk for parkinsonism.

Conclusions:

  • The link between FHpMD and EPS appears influenced by EPS subtype and patient age.
  • A common ATP1A3 genomic variation may be a susceptibility factor for antipsychotic-induced parkinsonism in an allele-dependent manner.
  • Further research into genetic predispositions can refine risk assessment for antipsychotic side effects.

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