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.
Psychological medicine
September 1, 2022
Benjamin S C Wade, Joana Loureiro, Ashish Sahib et al.
18 citations
Before serial ketamine infusion, brain structure, function, and connectivity measures predicted how much depressive symptoms changed afterward. In 60 patients with depression, machine learning models using pretreatment MRI scans explained 19% of variance in core mood and anhedonia symptoms, 27% in a depression subscale, and 1% in rumination reflection. Greater connectivity in the right medial prefrontal cortex, anterior cingulate, and posterior insula, along with lower kurtosis of a white-matter tract, predicted larger symptom reductions. Connectivity of the left posterior cingulate, left insula, and right superior parietal lobule predicted changes in rumination. These findings suggest that anterior default mode network and posterior insula connectivity may serve as biomarkers for antidepressant 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.