Preliminary evidence that ketamine alters anterior cingulate resting-state functional connectivity in depressed individuals
Laith Alexander, Peter C. T. Hawkins, Jennifer W. Evans, Mitul A. Mehta, Carlos A. Zarate
Translational Psychiatry December 3, 2023 Peer reviewed DOI: 10.1038/s41398-023-02674-1 via DOAJ
Summary
Ketamine's effects on brain connectivity differ across regions of the anterior cingulate cortex (ACC) in patients with treatment-resistant depression (TRD) and healthy volunteers. Specifically, ketamine altered resting-state functional connectivity in the subgenual ACC, which correlated with improvements in depression and anhedonia symptoms. The study highlights the importance of distinguishing ACC subregions to fully understand ketamine's antidepressant effects.
Study at a glance
| Design | double-blind randomized placebo-controlled crossover trial |
|---|---|
| Population | patients with treatment-resistant depression and healthy volunteers |
| Key finding | Ketamine differentially modulated resting-state functional connectivity in specific ACC subregions, correlating with improvements in depression scores in patients with treatment-resistant depression. |
Abstract
Abstract Activity changes within the anterior cingulate cortex (ACC) are implicated in the antidepressant effects of ketamine, but the ACC is cytoarchitectonically and functionally heterogeneous and ketamine’s effects may be subregion specific. In the context of a double-blind randomized placebo-controlled crossover trial investigating the clinical and resting-state fMRI effects of intravenous ketamine vs. placebo in patients with treatment resistant depression (TRD) vs. healthy volunteers (HV), we used seed-based resting-state functional connectivity (rsFC) analyses to determine differential changes in subgenual ACC (sgACC), perigenual ACC (pgACC) and dorsal ACC (dACC) rsFC two days post-infusion. Across cingulate subregions, ketamine differentially modulated rsFC to the right insula and anterior ventromedial prefrontal cortex, compared to placebo, in TRD vs. HV; changes to pgACC-insula connectivity correlated with improvements in depression scores. Post-hoc analysis of each cingulate subregion separately revealed differential modulation of sgACC-hippocampal, sgACC-vmPFC, pgACC-posterior cingulate, and dACC-supramarginal gyrus connectivity. By comparing rsFC changes following ketamine vs. placebo in the TRD group alone, we found that sgACC rsFC was most substantially modulated by ketamine vs. placebo. Changes to sgACC-pgACC, sgACC-ventral striatal, and sgACC-dACC connectivity correlated with improvements in anhedonia symptoms. This preliminary evidence suggests that accurate segmentation of the ACC is needed to understand the precise effects of ketamine’s antidepressant and anti-anhedonic action.