Synaptic Potentiation Is Critical for Rapid Antidepressant Response to Ketamine in Treatment-Resistant Major Depression
Biological Psychiatry, 04/26/2012Cornwell BR et al.
The findings suggest N–methyl–D–aspartate receptor (NMDAR) antagonism does not lead directly to increased cortical excitability hours later and thus might not be sufficient for therapeutic effects of ketamine to take hold. Rather, increased cortical excitability as depressive symptoms improve is consistent with the hypothesis that enhanced non–NMDAR–mediated glutamatergic neurotransmission via synaptic potentiation is central to the antidepressant effect of ketamine.
Twenty drug-free major depressive disorder patients received a single, open-label intravenous infusion of ketamine hydrochloride (.5 mg/kg).
Magnetoencephalographic recordings were made approximately 3 days before and approximately 6.5 hours after the infusion, whereas patients passively received tactile stimulation to the right and left index fingers and also while they rested (eyes-closed).
Antidepressant response was assessed by percentage change in Montgomery-Åsberg Depression Rating Scale scores.
Patients with robust improvements in depressive symptoms 230 min after infusion (responders) exhibited increased cortical excitability within this antidepressant response window.
Specifically, the authors found that stimulus-evoked somatosensory cortical responses increase after infusion, relative to pretreatment responses in responders but not in treatment nonresponders.
Spontaneous somatosensory cortical γ -band activity during rest did not change within the same timeframe after ketamine in either responders or nonresponders.
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