Temporal Dynamics of Antidepressant Ketamine Effects On Glutamine Cycling Follow Regional Fingerprints of Ampa and Nmda Receptor Densities

Introduction Subanesthetic dose of ketamine was repeatedly shown to improve depressive symptoms with a short latency of 24 hours. Objective We aimed to test if clinical time course of improvement is indeed mirrored by increased glutamine/glutamate ratio and if such effects would show a regional and temporal specificity in two anatomically and functionally distinct subdivisions of ACC. Method We used a glutamine sensitive magnetic resonance spectroscopy protocol at 7 Tesla to compare the longitudinal changes of glutamine/glutamate after 1 hour and 24 hours in pregenual ACC (pgACC, Figure 1A) and anterior mid-cingulate cortex (aMCC, Figure 1B) in 59 healthy controls which underwent a double-blind, placebo-controlled ketamine infusion. Result A significant interaction of time, region, and treatment was found (F = 3.881, p<0.028). Follow up analysis revealed that, only in pgACC and only after 24 hours, we found significantly increased glutamine/glutamate ratios in ketamine group compared with placebo (T = 2.331, p < 0.042) (Figure 2). We also found that the changes in pgACC over baseline are significant larger than changes in aMCC (T = 2.710, p