Info

val/val val/met BDNF Genotype met/met val/val val/met BDNF Genotype met/met

Figure 6. Relationship between BDNF genotype and left medial temporal lobe NAA/Cre. (From: Egan et al.27). The effect of genotype was F(i,3oi)=1.76, p<0.02.

Another genetic variation that has been associated with NAA/Cre is a single nucleotide polymorphism (SNP) in intron 2 of the metabotropic glutamate receptor 3 gene (GRM3). Egan et al.28 reported that the A allele at SNP rs6465084 was overtransmitted in families to offspring with schizophrenia and that it predicted important aspects of prefrontal function ranging from cognitive performance on a verbal fluency task and a memory task that require prefrontal and medial temporal processing, to cerebral activation measured with fMRI. Also MRSI provided evidence in this same direction: people carrying the A allele had lower NAA/Cre ratios in the DLPFC than G carriers. Similar effects were found across all groups studied (normal controls, patients with schizophrenia and their siblings), but, as also true for BDNF, this effect was weakest in the siblings and strongest in the normal controls (Figure 7). These results were recently confirmed by Steele et al.29 using 3T methodology in a new group of normal controls, as shown in figure 8.

Left DLPFC NAA/Cre

Left DLPFC NAA/Cre

GRM3 Genotype

GRM3 Genotype

Figure 7. Effect of GRM3 genotype at rs6465084 on NAA/Cre ratios in the Left DLPFC. These data were acquired at 1.5T. (From Egan et a/.28).

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