AKAP13, CACNA1, GRIK4 and GRIA1 genetic variations may be associated with haloperidol efficacy during acute treatment

Eur Neuropsychopharmacol. 2013 Aug;23(8):887-94. doi: 10.1016/j.euroneuro.2012.08.013. Epub 2012 Sep 11.


We previously investigated a sample of psychotic patients acutely ill and acutely treated with haloperidol in the search for genetic predictors of response at PANSS scores during the first month of treatment. In the present work we extend the analysis to a wider panel of genetic variations including SNPs harbored by genes whose products are involved in molecular pathways consistent with the latest results of genome-wide association studies (GWAS) of antipsychotic efficacy. 96 Patients were investigated. The results were replicated in an independent sample of bipolar manic patients treated with antipsychotics (n tot=470, the sample was retrieved from the STEP-BD). Outcomes were the PANSS variation through time in the first sample, and changes of mania symptomatology at any two consecutive observations in the public available STEP-BD replication sample. A list of variations harbored by AKAP13, CACNA1, GRIK4 and GRIA1 were found to be significantly associated with outcome in both samples (different set of variations for each sample). Results did not survived multiple testing in the original sample but were replicated in both samples. This finding stresses the relevance of the glutamatergic system and regulatory molecular cascades in antipsychotic response. Nonetheless, the level of significance and the indirect and incomplete replication mandate cautiousness and further replication.

Keywords: Antipsychotic; Gene; Haloperidol; PANSS; Pharmacogenetics.

MeSH terms

  • A Kinase Anchor Proteins / genetics
  • A Kinase Anchor Proteins / metabolism
  • Adult
  • Antipsychotic Agents / therapeutic use*
  • Bipolar Disorder / drug therapy
  • Bipolar Disorder / genetics
  • Bipolar Disorder / metabolism
  • Calcium Channels / genetics
  • Calcium Channels / metabolism
  • Drug Resistance / genetics*
  • Female
  • Genome-Wide Association Study
  • Germany
  • Haloperidol / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Minor Histocompatibility Antigens
  • Polymorphism, Single Nucleotide*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Psychiatric Status Rating Scales
  • Psychotic Disorders / drug therapy*
  • Psychotic Disorders / genetics
  • Psychotic Disorders / metabolism
  • Receptors, AMPA / genetics
  • Receptors, AMPA / metabolism
  • Receptors, Kainic Acid / genetics
  • Receptors, Kainic Acid / metabolism
  • Young Adult


  • A Kinase Anchor Proteins
  • AKAP13 protein, human
  • Antipsychotic Agents
  • CACNA1A protein, human
  • Calcium Channels
  • GRIK4 protein, human
  • Minor Histocompatibility Antigens
  • Proto-Oncogene Proteins
  • Receptors, AMPA
  • Receptors, Kainic Acid
  • Haloperidol
  • glutamate receptor ionotropic, AMPA 1