Human brain mapping
May 1, 2020
Joana R A Loureiro, Amber Leaver, Megha Vasavada et al.
65 citations
Both electroconvulsive therapy (ECT) and ketamine reduce amygdala reactivity to positive and negative emotional faces in people with treatment-resistant depression. In a naturalistic study of 44 patients (17 receiving ECT, 27 receiving ketamine), fMRI showed decreased amygdala response after both treatments. Subtle differences between treatments appeared in the dorsolateral prefrontal cortex and insula. Changes in brain activity in the inferior parietal cortex correlated with overall symptom improvement, while frontal region changes correlated with anxiety for negative faces and anhedonia for positive faces. The findings suggest common and distinct neural mechanisms underlying fast-acting antidepressant effects on emotion processing.
Translational Psychiatry
March 21, 2021
Jennifer L. Kruse, Megha M. Vasavada, Richard Olmstead et al.
47 citations
Lower baseline levels of the inflammatory marker interleukin-8 (IL-8) in females, but not males, trended toward predicting a better response to ketamine for depression. In 46 depressed patients receiving a single ketamine infusion, changes in IL-8 over time also differed by sex and treatment response: increasing IL-8 was associated with decreasing depression scores in females, while the opposite pattern appeared in males. Other inflammatory markers showed no significant relationships. These preliminary findings suggest that sex differences in IL-8 may help explain how ketamine works and could guide personalized depression treatment.
Translational psychiatry
July 30, 2020
Ashish K Sahib, Joana Ra Loureiro, Megha M Vasavada et al.
37 citations
Ketamine produces rapid antidepressant effects even in people with treatment-resistant depression, but how it alters brain function is not fully understood. In this study, 47 patients with treatment-resistant depression and 32 healthy controls performed a brain-imaging task measuring response inhibition. After one and then four intravenous ketamine infusions, 37 patients repeated the task. Brain activation decreased in regions involved in inhibitory control, including prefrontal and parietal areas and visual cortex, following repeated treatment. Patients who achieved remission had lower activation in the supplementary motor area before treatment, which then normalized toward control levels after ketamine. These changes in the supplementary motor area during response inhibition were linked to reduced depressive symptoms and may predict treatment outcome.
Psychological medicine
October 1, 2022
Ashish K Sahib, Joana R Loureiro, Megha Vasavada et al.
36 citations
Ketamine infusion therapy can rapidly relieve depression, but its effects on whole-brain functional connections are not well understood. In patients with major depressive disorder (MDD), baseline resting-state functional connectivity (FC) differed from healthy controls in the somatomotor network and between association and default mode networks. After one and four ketamine infusions, these disrupted FC patterns trended toward those of controls. Serial ketamine treatment significantly decreased FC between the cerebellum and the salience network. Patients who remitted showed higher pre-treatment FC between the cerebellum and striatum that decreased after treatment, while non-remitters showed the opposite pattern. Ketamine induces neurofunctional plasticity in cortico-striatal-cerebellar loops involving the salience network, which may serve as a biomarker for treatment response.
Brain and behavior
June 1, 2024
Brandon Taraku, Joana R Loureiro, Ashish K Sahib et al.
11 citations
Ketamine infusions alter brain connectivity in people with major depressive disorder, particularly in circuits involving the habenula and nucleus accumbens, which are linked to reward processing. After four infusions, changes in functional connections between these regions and visual, parietal, and cerebellar areas correlated with improvements in mood and anhedonia. For example, decreased variability in connectivity between the left habenula and right precuneus/visual cortex was associated with better mood, while altered connectivity between the left habenula and visual/parietal cortices and between the left nucleus accumbens and visual/parietal cortices correlated with reduced anhedonia. No such changes occurred in healthy controls.
medRxiv Preprint Server
December 1, 2023
Brandon Taraku, Joana R. Loureiro, Ashish K. Sahib et al.
1 citation
preprint
In major depressive disorder, ketamine infusions alter brain connectivity in networks involving the habenula and nucleus accumbens, regions central to reward processing. After four subanesthetic ketamine infusions given to 58 adults with depression, resting-state fMRI scans showed specific changes in static and dynamic functional connectivity between these regions and visual, parietal, and cerebellar areas. Decreased variability in connectivity between the left habenula and right precuneus and visual cortex, and between the right nucleus accumbens and right visual cortex, correlated with reduced depression severity. Reduced connectivity between the left habenula and visual/parietal cortices, and increased connectivity between the left nucleus accumbens and visual/parietal cortices, correlated with improvements in anhedonia. Ketamine appears to modulate overlapping habenula and nucleus accumbens functional pathways related to therapeutic response.
medRxiv
July 29, 2025
Artemis Zavaliangos‐petropulu, Ginny Ghang, Toni Boltz et al.
preprint
Treatment-resistant depression affects 30-50% of people with major depressive disorder. Electroconvulsive therapy and ketamine can relieve it, but how they work is unclear. This transcriptome analysis of peripheral blood from 37 people receiving electroconvulsive therapy, 60 receiving ketamine, and 35 non-depressed controls found no longitudinal changes in gene expression for either treatment after correcting for multiple comparisons. In the ketamine group, one gene (IGKV1-9) differed between remitters and non-remitters at baseline. In the electroconvulsive therapy group, six co-regulated gene modules differed at baseline between patients and controls. Pre-treatment gene expression differences may have predictive value, but larger studies are needed.
Imaging neuroscience (Cambridge, Mass.)
January 1, 2025
Brandon Taraku, Jason S Nomi, Artemis Zavaliangos-Petropulu et al.
Ketamine treatment alters how brain networks dynamically interact in people with treatment-resistant depression. After four ketamine infusions over two weeks, patients spent less time in a visual-network brain state and more time in a central-executive-network state. Transitions between the salience network and central executive network increased, while salience-to-visual transitions decreased. Reduced time in the salience-network state was linked to less rumination. Before treatment, depressed patients differed from healthy controls in these same dynamic patterns, suggesting ketamine may shift network dynamics toward a healthier profile.