Homer-1 polymorphisms are associated with psychopathology and response to treatment in schizophrenic patients

J Psychiatr Res. 2011 Feb;45(2):234-41. doi: 10.1016/j.jpsychires.2010.06.004. Epub 2010 Jul 3.


The HOMER 1 protein plays a crucial role in mediating glutamatergic neurotransmission. It has previously shown to be a candidate gene for etiology and pathophysiology of different psychiatric diseases such as schizophrenia. To identify genes involved in response to antipsychotics, subgroups of animals were treated with haloperidol (1 mg/kg, n = 11) or saline (n = 12) for one week. By analyzing microarray data, we replicated the observed increase of Homer 1 gene expression. Furthermore, we genotyped 267 schizophrenic patients, who were treated monotherapeutically with different antipsychotics within randomized-controlled trials. Psychopathology was measured weekly using the PANSS for a minimum of four and a maximum of twelve weeks. Correlations between PANSS subscale scores at baseline and PANSS improvement scores after four weeks of treatment and genotypes were calculated by using a linear model for all investigated SNP's. We found an association between two HOMER 1 polymorphisms (rs2290639 and rs4704560) and different PANSS subscales at baseline. Furthermore all seven investigated polymorphisms were found to be associated with therapy response in terms of a significant correlation with different PANSS improvement subscores after four weeks of antipsychotic treatment. Most significant associations have been shown between the rs2290639 HOMER 1 polymorphism and PANSS subscales both at baseline conditions and after four weeks of antipsychotic treatment. This is the first study which shows an association between HOMER 1 polymorphisms and psychopathology data at baseline and therapy response in a clinical sample of schizophrenic patients. Thus, these data might further help in detecting differential therapy response in individuals with schizophrenia.

MeSH terms

  • Adult
  • Animals
  • Antipsychotic Agents / therapeutic use*
  • Carrier Proteins / genetics*
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Frequency
  • Genome-Wide Association Study
  • Genotype
  • Haloperidol / therapeutic use*
  • Homer Scaffolding Proteins
  • Humans
  • Male
  • Middle Aged
  • Pharmacogenetics
  • Polymorphism, Single Nucleotide / genetics*
  • Psychiatric Status Rating Scales
  • Psychopathology
  • Rats
  • Rats, Long-Evans
  • Schizophrenia* / drug therapy
  • Schizophrenia* / genetics
  • Schizophrenia* / pathology
  • Schizophrenic Psychology*
  • Young Adult


  • Antipsychotic Agents
  • Carrier Proteins
  • Homer Scaffolding Proteins
  • Haloperidol