Association between type-three metabotropic glutamate receptor gene (GRM3) variants and symptom presentation in treatment refractory schizophrenia

摘要

Objective Positive associations between polymorphisms in the type-three metabotropic glutamate receptor gene (GRM3) and the pathogenesis of schizophrenia as well as response to antipsychotic treatment have been reported. The objective of this study was to determine whether refractory psychiatric symptoms in antipsychotic non-responders are related to polymorphisms in GRM3. Methods Ninety-five treatment refractory schizophrenia participants were enrolled. Prior to a medication switch, global psychopathology and negative symptoms were rated. These participants were genotyped for seven markers in GRM3. Genotype associations with symptoms were assessed. Results Two markers in GRM3 (rsl989796 and rsl476455), were associated with the presence of refractory global symptoms as measured by the Brief Psychiatric Rating Scale (BPRS) Total scores. Participants with an rsl476455_CC genotype had significantly higher BPRS scores than A-carriers (55.1 +- 10.4 vs. 48.3 +-9.2; F=7.6, p = 0.0071). Additionally, participants with the rsl989796_CC genotype had significantly higher BPRS scores than T-carriers (50.1 +- 5.7 vs. 55.8 +- 10.5, F=1A, p = 0.0091). No evidence for significant associations with negative symptoms was observed. Conclusions Polymorphisms in the GRM3 gene may be associated with refractory global psychosis symptoms but not negative symptoms in persons with schizophrenia.