FOXP2 expression and gray matter density in the male brains of patients with schizophrenia

Abstract

Common genetic variants ofFOXP2may contribute to schizophrenia vulnerability, but controversial results have been reported for this proposal. Here we evaluated the potential impact of the commonFOXP2rs2396753 polymorphism in schizophrenia. It was previously reported to be part of a risk haplotype for this disease and to have significant effects on gray matter concentration in the patients. We undertook the first examination into whether rs2396753 affects the brain expression ofFOXP2and a replication study of earlier neuroimaging findings of the influence of this genetic variant on brain structure.FOXP2expression levels were measured in postmortem prefrontal cortex samples of 84 male subjects (48 patients and 36 controls) from the CIBERSAM Brain and the Stanley Foundation Array Collections. High-resolution anatomical magnetic resonance imaging was performed on 79 male subjects (61 patients, 18 controls) using optimized voxel-based morphometry. We found differences inFOXP2expression and brain morphometry depending on the rs2396753, relating lowFOXP2mRNA levels with reduction of gray matter density. We detected an interaction between rs2396753 and the clinical groups, showing that heterozygous patients for this polymorphism have gray matter density decrease and lowFOXP2expression comparing with the heterozygous controls. This study shows the importance of independent replication of neuroimaging genetic studies ofFOXP2as a candidate gene in schizophrenia. Furthermore, our results suggest that theFOXP2rs2396753 affects mRNA levels, thus providing new knowledge about its significance as a potential susceptibility polymorphism in schizophrenia.