Translational psychiatry
July 27, 2024
Rubén Herzog, Florentine Marie Barbey, Md Nurul Islam et al.
13 citations
Ketamine increases redundancy in brain dynamics—copies of the same information retrievable from three or more electrodes—most notably in the alpha frequency band, as measured by portable low-density EEG. In a double-blind crossover trial with 30 male adults, racemic ketamine compared to saline infusion produced greater redundancy during resting state, linked to dissociative shifts in consciousness. During an auditory oddball task, the effect was stronger for predictable standard stimuli than for deviant ones. Associations between ketamine's high-order interactions and experiences of derealization were observed, suggesting these measures capture pharmacological alterations in consciousness.
The international journal of neuropsychopharmacology
June 1, 2024
Thomas Liebe, Lena Vera Danyeli, Zümrüt Duygu Sen et al.
5 citations
Ketamine, an NMDA antagonist used as a rapid-acting antidepressant, disrupts the functional connectivity between the locus coeruleus (LC) and the thalamus, which is linked to a reduction in behavioral alertness. In a placebo-controlled, cross-over study with 35 healthy male participants (average age 25.1 years), ultra-high field 7T functional MRI revealed that acute disruption of the LC alertness network by ketamine correlates with decreased alertness. These findings highlight ketamine's effects beyond the glutamatergic system, suggesting a new mechanism involving noradrenergic pathways that may contribute to its antidepressant properties.
Journal of psychiatric research
April 1, 2024
Lena Vera Danyeli, Zümrüt Duygu Sen, Lejla Colic et al.
3 citations
In healthy men, a thinner posterior cingulate cortex (PCC) is linked to a stronger feeling of disembodiment after a low dose of ketamine, a drug that can rapidly relieve depression. The study measured cortical thickness in two brain regions—the PCC and the pregenual anterior cingulate cortex (pgACC)—and found that only PCC thickness correlated with the altered sense of self (disembodiment). No such link appeared for the pgACC. These results suggest the PCC plays a key role in ketamine's effects on self-experience, a feature shared with other fast-acting antidepressants that also produce psychedelic-like effects.
Brain, behavior, and immunity
July 5, 2026
Bruno Pedraz-Petrozzi, Marta Marszalek-Grabska, Emilia Fornal et al.
In adults with treatment-resistant depression receiving six intravenous ketamine infusions over three weeks, higher baseline levels of the neuroprotective metabolite kynurenic acid (KYNA) in the kynurenine pathway were associated with greater symptom improvement by day 18. KYNA remained stable over time and did not track with symptom changes, suggesting it acts as a trait-like marker rather than a state-dependent one. Early shifts toward the neurotoxic branch of the pathway (kynurenine and 3-hydroxykynurenine) were linked to reductions in hopelessness and suicidality scores after the first infusion. These exploratory findings indicate that a kynurenine pathway profile biased toward neuroprotective metabolites may inform future biomarker studies of ketamine response, but require validation in larger samples.
Frontiers in psychiatry
January 1, 2025
Leonard Marx, Zümrüt Duygu Sen, Lena Vera Danyeli et al.
Ketamine's rapid antidepressant effects are thought to involve glutamate signaling and brain-derived neurotrophic factor (BDNF), but how these two factors interact is unclear. In a randomized, placebo-controlled crossover study with 35 healthy men, researchers measured glutamate levels in the pregenual anterior cingulate cortex using 7 Tesla magnetic resonance spectroscopy and plasma BDNF levels before and after infusions of S-ketamine or placebo. A significant interaction emerged between treatment condition and changes in glutamate on BDNF level changes, with a trend-level positive correlation between glutamate and BDNF changes only in the ketamine group. These findings offer initial in vivo evidence that ketamine's influence on BDNF is tied to its glutamatergic action.