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

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Li, M., Demenscu, R., Metzger, C., & Walter, M. (2015). Temporal Dynamics of Antidepressant Ketamine Effects On Glutamine Cycling Follow Regional Fingerprints of Ampa and Nmda Receptor Densities. Poster presented at 23rd European Congress of Psychiatry (EPA 2015), Wien, Austria.


Cite as: http://hdl.handle.net/21.11116/0000-0000-F85E-0
Abstract
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<0.022) at 24 hours after ketamine infusion. Changes of glutamine/glutamate ratios were mainly driven by glutamine but not glutamate levels. Conclusion We found that elevated glutamine/glutamate after a single subanesthetic dose of ketamine infusion was specific to pgACC, a region previously reported glutamategic deficit in MDD. This change of glutamine/glutamate in the pgACC also showed a temporal specificity at 24 hours after infusion.