Homer-1 polymorphisms are associated with psychopathology and response to treatment in schizophrenic patients.
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.
Spellmann
Ilja
I
Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University of Munich, Nußbaumstrasse 7, 80336 Munich, Germany. ilja.spellmann@med.uni-muenchen.de
Rujescu
Dan
D
Musil
Richard
R
Mayr
Andreas
A
Giegling
Ina
I
Genius
Just
J
Zill
Peter
P
Dehning
Sandra
S
Opgen-Rhein
Markus
M
Cerovecki
Anja
A
Hartmann
Annette M
AM
Schäfer
Martin
M
Bondy
Brigitta
B
Müller
Norbert
N
Möller
Hans-Jürgen
HJ
Riedel
Michael
M
D000328:Adult; D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D005838:Genotype; D006220:Haloperidol / Q000627:therapeutic use*; D000072233:Homer Scaffolding Proteins; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D011599:Psychopathology; D051381:Rats; D020318:Rats, Long-Evans; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D012565:Schizophrenic Psychology; D055815:Young Adult
D014150:Antipsychotic Agents; D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D006220:Haloperidol