Together with the demonstrated downregulation of SLC6A15 expression in stress-susceptible mice, human gene expression and imaging data support a role for hippocampal SLC6A15 function in stress sensitivity and the pathophysiology of MD. This would be in line with a proposed role of the SLC6A15 transporters in neuronal metabolism and the provision of substrates for neurotransmitters, and specifically glutamate synthesis (Broer et al., 2006). Thus, decreased hippocampal NAA and by extension glutamate neurotransmission (Benarroch, 2008), related to genetic factors, may limit excitatory signalling capacity with secondary effects on stress response regulation and hippocampal function in general (Herman et al., 2003).
