Abstract
Background
Ketamine-induced antidepressant effect has been reported in animal and human studies. The rapid efficacy of ketamine, a non-completive NMDA receptor antagonist, indicates different mechanisms compared to currently available drugs. However, the accompanying adverse effects and association to antidepressant properties remain unknown. This study investigated the change of mean global neuronal activity, also known as global signal (GS), 1h and 24h after ketamine infusion, and the relationship with the acute dissociative experience.
Methods
In a randomized, double-blind, placebo-controlled study, 81 healthy controls received single subanesthetic dose of ketamine (0.5 mg/kg within 40 min) or saline. For each subject, resting-state fMRI were acquired at baseline, 1h, and 24h post-infusion at 7T scanner. The dissociative side effects were evaluated using Clinician Administered Dissociative States Scale (CADSS) right after the infusion.
EPI data were preprocessed using scripts from the 1000 functional connectome project (FCP, version 1.1-beta). GS was extracted and transformed into Z-Score, and its change was assessed by implementing Teager-kaiser operator. Thirty-two ketamine and thirty placebo subjects were tested at threshold p<0.05.
Results
Larger fluctuation of GS was found 1 hour after ketamine administration (t=2.09, p=0.04). Moreover, in ketamine group, the GS at 1 hour associated with total CADSS (r=−0.353, p=0.04), more specifically with subscale derealization (r=−0.466, p=0.007).
Conclusions
GS changes and associated adverse effects were observed only in the acute phase after ketamine administration. This could imply that long-term antidepressant results are downstream effects from the acute phase, and GS can be seen as an early marker of underlying neuronal activity induced by ketamine.
