What is it about?
This study investigates whether a single infusion of low-dose ketamine is associated with changes in brain network integrity in patients with treatment-resistant depression (TRD) and suicidal ideation. Using resting-state functional MRI and graph theory–based network metrics, the authors compared brain connectivity patterns before infusion and three days after treatment between ketamine and midazolam control groups.
Why is it important?
Disruptions in large-scale brain networks have been implicated in treatment-resistant depression and suicidality. Examining whether ketamine is associated with short-term changes in functional brain network organization may help clarify potential neurofunctional mechanisms underlying its rapid antidepressant and antisuicidal effects, while also highlighting the limits of linking neural changes directly to clinical outcomes.
Main findings
- Patients receiving ketamine showed greater reductions in depressive and suicidal symptom scores compared with the control group at day 3 post-infusion.
- Ketamine was associated with increased degree centrality in the right thalamus and increased degree centrality and clustering coefficient in the angular gyrus, a key region of the default mode network.
- These network changes were not present at baseline and differed from patterns observed in the control group.
- After correction for multiple comparisons, changes in network metrics were not significantly correlated with changes in depressive or suicidal symptoms.
What do the authors argue?
The authors suggest that low-dose ketamine may improve brain network integrity in patients with TRD and suicidal ideation, particularly within the default mode network and thalamic regions. However, because network changes were not robustly associated with symptom changes, they emphasize that these findings should be interpreted as neurofunctional correlates rather than direct mechanisms, underscoring the need for larger studies to clarify brain–symptom relationships following ketamine treatment.
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You can find the paper here.