The influence of polymorphism for gene RGS4 (Regulator of G-protein Signaling 4) on regional brain metabolism (18FDG PET) and phenotypic variables in schizophrenia
Abstrakt
RGS4 represents a positional and functional candidate gene for schizophrenia confirmed by several studies in independent samples. In a group of 63 patients with schizophrenia, we have genotyped four SNPs (1,4,7,18) which have previously been associated with schizophrenia, individually or as part of haplotype.
We evaluated the influence of candidate SNPs on phenotypic characteristics and regional brain metabolism measured by 18FDG PET. Neuroimaging data were treated by SPM99.
We found lower metabolism bilaterally in basal ganglia (pLESS-THAN OR EQUAL TO0.05, corrected) in the risky G-allele carriers in SNP 7. In SNP 1, the trend for lower metabolism associated with the G-allele in the right prefrontal cortex was detected (pLESS-THAN OR EQUAL TO0.001).
The risky G-allele was connected with lower expression of negative symptoms (SNP7) and later onset of schizophrenia (SNP 7,18).Our results support the role of basal ganglia and the prefrontal cortex in the mechanism of how the RGS4 polymorphism influrences schizophrenia. We formulate the hypothesis of specific RGS4 phenotype of schizophrenia charakterized by the lower expression of negative symptoms and later onset which differs from the schizophrenia subtypes associated with candidate genes regulating neurodevelopment and synaptic structure.