Homer 1 and metabotropic glutamate-receptor 5 polymorphisms are associated with response to treatment in schizophrenic patients

A hypofunction of glutamatergic NMDA-currents is discussed as pathophysiologic correlative of symptoms in schizophrenia. Polymorphisms within metabotropic glutamate receptors (mGluRs) were found to be associated with schizophrenia. The Homer proteins are part of the postsynaptic density in glutamatergic neurons and bind to mGluR 5 receptors. We investigated ten SNPs in the mGlu5 receptor and five SNPs in the Homer gene and their relationships to response in therapy. We genotyped 212 schizophrenic patients, who were treated with atypical antipsychotics. Psychopathology was measured weekly using the PANSS for a minimum of six weeks. 412 healthy subjects served as controls for allele distribution. The homocygote TT-allele carriers of the SNP rs979763 (T/C) of the mGlu5 receptor showed a statistically significant reduction in PANSS-negative and –global scales in comparison to the combined TC/CC-allele carriers. The combined GG/GT allele carriers of the SNP rs1993842 (G/T)of the mGlu5 receptor displayed almost no reduction in PANSS-negative scores compared to the TT homozygotes which was statistically significant. The homozygote AA allele carriers of SNP rs10039490 of the Homer-1 gene had a significantly more pronounced reduction in PANSS-positive and -global scores. This is the first study which shows an association between therapy response of negative symptoms in schizophrenia and the mGlu5 receptor gene and positive symptoms and the Homer-1 gene.