Dysbindin C-A-T haplotype is associated with thicker medial orbitofrontal cortex in healthy population

Abstract

The dysbindin (dystrobrevin-binding protein 1) gene has been indicated as one of the most important schizophrenia susceptibility genes. Several genetic variations of this gene have been investigated by using an "intermediate phenotype" approach showing a particular detrimental effect on the prefrontal function in schizophrenic patients. However, the nature of dysbindin function within the brains of healthy individuals is poorly understood, in particular as concerns brain anatomy. We examine relationships between a previously implicated three marker C-A-T dysbindin haplotype and regional cortical thickness in a wide population genotyped for risk carriers (n=14) and non-risk carriers (n=93). Surface-based analysis of the cortical mantle showed that the dysbindin haplotype was associated with structural differences in the medial orbitofrontal cortex, where the risk carriers showed the highest cortical thickness values and the non-risk carriers the lowest. Our study extends previous evidence found on schizophrenic patients to the healthy population, demonstrating the influence of dysbindin risk variants on the neuronal architecture of a specific brain region relevant to the neuropathology of schizophrenia.