To further characterize the functional relevance of the identified locus, we analyzed genotypic influences of associated SNPs on pre-mortem human hippocampus and lymphoblastoid cell line expression profiles. We also employed in vivo high resolution structural magnetic resonance imaging (MRI) and proton nuclear magnetic resonance spectroscopy (1H-NMR) with a focus on the hippocampal formation. We selected this brain region based on our gene expression results and because decreased neuronal integrity in this brain region had previously been identified as a risk factor for major depression (Frodl et al., 2002). Moreover, we investigated a possible role of the candidate locus in mediating stress vulnerability by interrogating its hippocampal expression in a well established mouse model of chronic social stress (Schmidt et al., 2007) as chronic stress represents an established risk factor for MD (Wang, 2005).
