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.
Translational Psychiatry
December 3, 2023
Laith Alexander, Peter C. T. Hawkins, Jennifer W. Evans et al.
26 citations
Ketamine's antidepressant effects involve changes in brain connectivity that depend on which part of the anterior cingulate cortex (ACC) is examined. In a double-blind, placebo-controlled crossover trial, patients with treatment-resistant depression and healthy volunteers received intravenous ketamine or placebo. Two days later, resting-state functional connectivity between ACC subregions and other brain areas differed between groups. Changes in perigenual ACC connectivity to the insula correlated with improved depression scores. Subgenual ACC connectivity was most altered by ketamine compared to placebo, and changes in its connectivity to other ACC subregions and the ventral striatum correlated with reduced anhedonia. Accurate ACC segmentation is needed to understand ketamine's effects.
Frontiers in Neuroimaging
June 27, 2023
Vasileia Kotoula, Jennifer W. Evans, Claire Punturieri et al.
26 citations
Functional magnetic resonance imaging (fMRI) can identify brain areas linked to depression symptoms and potential treatment targets. A review of fMRI studies on selective serotonin reuptake inhibitors (SSRIs) and ketamine found that both conventional and fast-acting antidepressants normalize amygdala hyperactivity in response to negative emotional stimuli, suggesting a common pathway for antidepressant action. Ketamine's rapid effects on brain activity and connectivity also trend toward normalizing depression-related abnormalities. While fMRI shows promise for identifying treatment targets, improved methodology and study design are needed before its findings can be used as primary clinical trial outcomes.
Progress in Brain Research
January 1, 2023
Vasileia Kotoula, Jennifer W. Evans, Claire Punturieri et al.
17 citations
Imaging studies of treatment-resistant depression (TRD) have examined brain activity, structure, and metabolite concentrations to identify critical areas of investigation and potential treatment targets. This chapter reviews findings from structural MRI, functional MRI, and magnetic resonance spectroscopy. Decreased connectivity and metabolite concentrations in frontal brain areas appear to characterize TRD, though results are not consistent across studies. Treatments including rapid-acting antidepressants and transcranial magnetic stimulation have shown some efficacy in reversing these changes while alleviating depressive symptoms. However, few TRD imaging studies exist, often with small sample sizes or varied methods, making firm conclusions difficult. Larger studies with unified hypotheses and data sharing could improve characterization of the illness and identify new treatment targets.
Scientific Reports
February 24, 2024
Jennifer W. Evans, Morgan C Graves, Allison C. Nugent et al.
9 citations
The hippocampus and amygdala are brain regions involved in major depressive disorder (MDD) and its treatment. Preclinical work suggests antidepressants, including ketamine, can reverse stress-related changes in these areas. Clinical studies show reduced volumes in MDD, worsened by early life stress and repeated episodes. This analysis of structural MRI data from a prior double-blind, placebo-controlled, crossover trial examined changes in hippocampal and amygdalar subfield volumes after ketamine treatment. Participants included healthy volunteers and unmedicated individuals with treatment-resistant depression scanned at baseline and twice after a single ketamine or saline infusion. At 10 days post-infusion, a slight increase in whole left amygdalar volume was observed in the ketamine group among those with depression. No other differences were found between groups at either 3T or 7T field strength.