Genetic polymorphisms of the RGS4 and dorsolateral prefrontal cortex morphometry among first episode schizophrenia patients

Abstract

Polymorphisms of the gene encoding the regulator of G-protein signaling subtype 4 (RGS4) may confer risk for schizophrenia.¹ DNA microarray studies of postmortem brain samples have shown RGS4 underexpression in the dorsolateral prefrontal cortex (DLPFC, area 9), motor and visual cortices in schizophrenia patients relative to control subjects.² Underexpression of RGS4 in DLPFC is pathophysiologically significant because DLPFC pathology in schizophrenia has been supported by neurocognitive,^3,4 structural⁵ and functional^6,7 imaging, postmortem,⁸ cellular^9,10 and molecular¹¹ pathological studies. For these reasons, we examined the association of DLPFC gray matter volume with RGS4 polymorphisms in a series of antipsychotic-naïve first-episode schizophrenia patients and control subjects. We hypothesized that volumetric alterations of the DLPFC would be associated with RGS4 polymorphisms and that these differences would be more pronounced in patients than in controls. We observed robust volumetric differences across the genotypes in the pooled sample of patients and control subjects; when separately analyzed, we observed differences within the patient group (n=30) but not in control subject (n=27) group. The findings suggest that RGS4 polymorphisms may contribute to structural alterations in the DLPFC.