Molecular-genetic dissection of anxiety/depression: From HAB phenotype to functional SNP

Two Wistar rat lines exhibiting either extremely high (HAB) or low (LAB) anxiety-related behavior on the EPM were established as a reliable psychopathological animal model for anxiety disorders and comorbid depression. In HABs neuroendocrine phenotyping revealed a pathological HPA axis function in correlation with AVP over-expression and -release within the PVN. The results led us to suggest AVP as a candidate gene of trait anxiety/depression. Whereas LABs all contained wildtype sequences, HABs showed 10 SNPs within the regulatory region of the AVP gene. One SNP in the distal promoter region contains a DNA-binding site of a transcriptional repressor which colocalizes with AVP. The hypothesis that reduced binding of this repressor to HAB alleles, found in vitro, may underlie, at least partly, AVP over-expression was reinforced by co-transfection experiments showing less inhibition of promoter activity in the HAB case.