Homer-1 polymorphisms are associated with psychopathology and response to treatment in schizophrenic patients |
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Authors: | Ilja Spellmann,Dan Rujescu,Andreas Mayr,Just Genius,Sandra Dehning,Anja Cerovecki,Martin Schä fer,Norbert Mü ller,Michael Riedel |
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Affiliation: | a Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University of Munich, Nußbaumstrasse 7, 80336 Munich, Germany b Psychiatric Clinic, Vinzenz-von-Paul-Hospital, Rottweil, Germany |
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Abstract: | 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. |
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Keywords: | Homer 1 Schizophrenia Antipsychotics Therapy response Pharmacogenetics Glutamate |
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