Neurophysiological evidence that frontoparietal connectivity and GABA-A receptor changes underpin the antidepressant response to ketamine.
Translational psychiatry February 24, 2024 Rachael L Sumner, Rebecca L McMillan, Anna Forsyth et al. 7 citations
Ketamine's antidepressant effects may be driven by acute changes in brain connectivity and GABA receptor dynamics, not primarily by NMDA receptor blockade. In 30 patients with major depressive disorder, resting-state EEG was recorded before and during a 0.44 mg/kg ketamine infusion. Computational modeling revealed a significant increase in parietal-to-frontal AMPA-mediated connectivity and a significant decrease in the frontal GABA time constant. Both changes correlated with antidepressant response. NMDA receptor changes did not survive correction and were not correlated with symptom improvement. The findings suggest that acute fronto-parietal connectivity and GABA-A/AMPA receptor dynamics mediate ketamine's antidepressant properties.