Pharmacogenetics of therapy response in schizophrenia

Pharmacogenetics firstly focussed on classical drug targets like dopaminergic or serotonergic receptors, but currently also developmental and regulatory genes presumably associated with effects of antipsychotic therapy are identified. The aim of this study was to investigate associations between therapy response in schizophrenic patients and different polymorphisms previously been identified within a genome wide array in rodents treated with MK-801 and/or haloperidol combined with some well-known schizophrenia candidate genes. We genotyped for 200 different polymorphisms in 285 schizophrenic patients treated with different antipsychotics. Psychopathology was measured weekly using the PANSS scale. Correlations between PANSS scores at baseline, PANSS improvement scores after four weeks of treatment and genotypes were calculated. We found significant associations between some candidate genes (e.g. D2- or 5HT1A-receptors) and different PANSS subscales at baseline and after four weeks of treatment. Furthermore, we identified associations between genes from the animal model and psychopathology at both time points. Some of them have already been described in the literature (e.g. Homer1 or Phospholipase C), but most of them were not related to schizophrenia or therapy response by now (e.g. PLEKHA6 or CLIC6). This indicates an involvement of genes in the pathophysiology of schizophrenia apart from yet known candidate genes and might help in detecting differenzial therapy response.