Ketamine-Associated Brain Changes: A Review of the Neuroimaging Literature
This review (2018) examines the neural correlates of ketamine-associated brain changes in patients with depression. Although ketamine affects different areas of the brain in various ways, its most notable effects were found in the subgenual anterior cingulate cortex, posterior cingulate cortex, prefrontal cortex, and hippocampus. Ketamine affects emotional blunting, which may be associated with reduced limbic responses to emotional stimuli, and increase neural activity in reward processing. It also reduces brain activation in regions, such as the Default Mode Network (DMN), associated with self-monitoring, which may be linked to its dissociative effects.
Authors
- Daniel Ionescu
Published
Abstract
Major depressive disorder (MDD) is one of the most prevalent conditions in psychiatry. Patients who do not respond to traditional monoaminergic antidepressant treatments have an especially difficult-to-treat type of MDD termed treatment-resistant depression. Interestingly, subanesthetic doses of ketamine-a glutamatergic modulator-have shown great promise for rapidly treating patients with the most severe forms of depression. As such, ketamine represents a promising probe for understanding the pathophysiology of depression and treatment response. Through neuroimaging, ketamine’s mechanism may be elucidated in humans. Here, we review 47 articles of ketamine’s effects as outlined by neuroimaging studies. Taken together, some important brain areas emerge, especially the subgenual anterior cingulate cortex. Furthermore, ketamine may decrease the ability to self-monitor, increase emotional blunting, and increase activity in reward processing. However, further studies are necessary to elucidate ketamine’s mechanism of antidepressant action.
Research Summary of 'Ketamine-Associated Brain Changes: A Review of the Neuroimaging Literature'
Introduction
Major depressive disorder (MDD) is common and often debilitating; a substantial subgroup—treatment-resistant depression (TRD), typically defined as failure to respond to at least two adequate antidepressant trials—carries high personal and economic burden. Subanesthetic doses of ketamine produce rapid (within hours), robust and often short‑to‑medium term antidepressant effects, with clinical studies reporting about 50% of TRD patients exhibiting substantial symptom reduction within 24 hours of a single intravenous dose. Preclinical work implicates NMDA receptor antagonism, an acute glutamate surge and downstream activation of synaptogenic pathways such as mTOR, but human neuroimaging findings about ketamine’s mechanism have been inconsistent and incomplete. Ionescu and colleagues set out to review the human neuroimaging literature to identify convergent brain regions and functional changes associated with ketamine, emphasising studies of patients with MDD but also including research in healthy volunteers because of the relative paucity of patient imaging. The review focuses on multiple imaging modalities (PET, MRS, fMRI, rsfMRI, MEG, diffusion and structural MRI), and aims to relate neuroimaging findings to clinical metrics (for example dissociation, baseline activity, and treatment response) to better characterise ketamine’s antidepressant mechanism and to suggest regions for future study.
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Ionescu, D. F., Felicione, J. M., Gosai, A., Cusin, C., Shin, P., Shapero, B. G., & Deckersbach, T. (2018). Ketamine-Associated Brain Changes: A Review of the Neuroimaging Literature. Harvard Review of Psychiatry, 26(6), 320-339. https://doi.org/10.1097/hrp.0000000000000179
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