Molecular Psychiatry
September 14, 2020
A. Mkrtchian, Jennifer W. Evans, C. Kraus et al.
110 citations
Ketamine increased fronto-striatal functional connectivity in people with treatment-resistant major depression toward levels seen in healthy volunteers, while shifting connectivity in healthy volunteers toward a state similar to depressed participants under placebo. These effects occurred largely without changes in inflammatory markers (C-reactive protein) and were associated with both acute and sustained symptom improvements in the depressed group. Ketamine thus normalized reward-related brain circuitry in depression but disrupted it in healthy individuals, highlighting the potential importance of this circuitry in ketamine's mechanism of action for motivational symptoms.
Drug Discovery Today
February 1, 2023
J. Johnston, Maximillian Greenwald, I. Henter et al.
64 citations
Stress triggers inflammation in the brain, a pattern also seen in the blood of people with depression. This stress-induced inflammation may contribute to treatment-resistant depression. The rapid-acting antidepressant ketamine works partly by reducing inflammation through effects on the HPA axis, the kynurenine pathway, or by suppressing cytokines. Understanding the link between ketamine, inflammation, and stress could reveal how ketamine works and lead to new rapid-acting antidepressants that target inflammation.
Current topics in behavioral neurosciences
March 22, 2022
Marina Kojić, J. Saelens, B. Kadriu et al.
11 citations
Ketamine, approved for treatment-resistant depression, and serotonergic psychedelics both show rapid antidepressant effects. Although they act on different primary targets, both may restore synaptic deficits and reconfigure brain networks. A glutamate surge activates AMPA receptor throughput and increases BDNF levels. Understanding these shared mechanisms could guide development of new rapid-acting antidepressants with fewer side effects.
October 23, 2018
B. Kadriu, Subha Subramanian, Z. Deng et al.
preprint
Major depressive disorder (MDD) is common, debilitating, and linked to suicide risk. Standard antidepressants can take weeks to work and have low remission rates, with about a third of patients not fully responding. Newer therapies targeting the glutamatergic system, such as ketamine, offer rapid antidepressant effects and high remission rates. This chapter reviews evidence for several novel therapeutics—ketamine, esketamine, nitrous oxide, scopolamine, GLYX-13, and buprenorphine—as well as interventional techniques like sleep deprivation. Ketamine and esketamine also rapidly reduce suicidal thoughts, making them useful in emergencies. Pivotal drug trials using rodents, neuroimaging, and electrophysiological studies are also reviewed to understand the neurocircuitry underlying MDD.