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RESEARCH PRODUCT

229 – ERBB4 genotype effects on human brain structure

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Background:Disturbed functional and structural brain connectivity in schizophrenia has been shown in a large number of studies. There is evidence from several neuroimaging and post mortem studies that altered neuronal myelination may in part account for this deficit. Recent investigations have suggested that variations of the genes that encode the Neuregulin 1 (NRG1) ErbB4 receptor complex might be associated with schizophrenia illness. As NRG1 and ErbB4 have been implicated in myelination and neuronal proliferation. We investigated whether cerebral micro and macrostructure is predicted by two risk haplotypes of the ErbB4 gene. Methods: The effects of two single-nucleotide polymorphisms (SNPs) rs2289086 and rs4673628 were investigated by diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) analysis in 51 healthy subjects (mean age 22.6±1.8 years). Reaction time (RT) was measured during an attentional paradigm (visual oddball). Results: For both rs2289086 and rs4673628, we found higher fractional anisotropy (FA) in the A/A genotype group in left temporal lobe white matter. In addition, higher FA in the rs4673628 A/A genotype group was demonstrated in the subventricular zone. Conclusions: As FA is considered to index structural integrity of WM, to which neuronal fiber myelination is contributing, our results suggest that variations of the ErbB4 genotype may confer risk for schizophrenia illness via its impact on structural connectivity in human brain. References: Konrad A, Winterer G (2007). Schizophr Bull (online). Nicodemus KK, et al. (2006). Mol Psychiatry 11(12): 1062–5. Silberberg G, et al. (2006). Am J Med Genet B Neuropsychiatr Genet 141(2): 142–8.