These analyses were complemented by analyzing 1H-NMR markers of hippocampal integrity, including N-acetyl aspartate (NAA). While NAA serves mainly as marker of neuronal viability, it is also regarded as reservoir for glutamate (Benarroch, 2008). To investigate genotype effects of left hippocampal neurochemistry we focused on healthy, non-medicated control subjects (N=81) as mood state and medication might influence hippocampal neurochemistry. Multivariate analysis detected a significant genotype effect of rs1031681 on hippocampal metabolites (Wilks’ lambda: 0.683, F2,75=2.976, p=0.002) with univariate comparisons pointing towards NAA (F2,75=6.143, p=0.003, pcorr<0.05). More specifically, A-risk-allele-carriers of rs1031681 showed lower levels of hippocampal NAA and glutamate/glutamine (Glx) indicating impaired neuronal integrity and Glx signalling already in healthy carriers (NAA: F1,76=5.575, p=0.021; Glx: F1,76=5.752, p=0.019; Cr: F1,76=4.009, p=0.049, fig. S4b). For NAA, a similar effect was detected for A-carriers of rs1545843 (F2,75=5.333, p=0.024).
