Thalamocortical functional connectivity and rapid antidepressant and antisuicidal effects of low-dose ketamine infusion among patients with treatment-resistant depression.
Pei-Chi Tu, Wan-Chen Chang, Tung-Ping Su, Wei-Chen Lin, Cheng-Ta Li, Ya-Mei Bai, Shih-Jen Tsai, Mu-Hong Chen
Molecular psychiatry January 1, 2025 DOI: 10.1038/s41380-024-02640-3 via PubMed
Summary
AI-generated from the abstractIn two clinical trials involving a total of 96 patients with treatment-resistant depression, a single low dose of ketamine altered specific connections between the thalamus and frontal brain regions, measured by resting-state functional MRI three days after infusion. Some thalamocortical connections increased and others decreased in the ketamine groups compared to placebo or midazolam groups. However, these brain connectivity changes were not statistically significantly linked to improvements in depression or suicidal thoughts after correcting for multiple comparisons. The results suggest that while ketamine may modify thalamocortical connectivity, whether these changes underlie its antidepressant and antisuicidal effects remains uncertain and requires further study.
Study at a glance
| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 96 |
| Population | Patients with treatment-resistant depression (48 with TRD and 48 with TRD and strong suicidal ideation) |
| Interventions | Ketamine normal saline placebo midazolam |
| Dose | single subanesthetic dose |
| Duration | 3 days after infusion |
| Topics | Depression |
| Keywords | Ketamine therapy Neuroscience Brain connectivity Mental health treatment |
| Citations | 13 |
| Key finding | Ketamine altered thalamocortical connectivity in patients with treatment-resistant depression, but these changes were not significantly associated with clinical symptom improvements after correction for multiple comparisons. |
Abstract
Previous studies have shown an association between the thalamocortical dysconnectivity and treatment-resistant depression (TRD). Whether a single subanesthetic dose of ketamine may change thalamocortical connectivity among patients with TRD is unclear. Whether these changes in thalamocortical connectivity is associated with the antidepressant and antisuicidal effects of ketamine treatment is also unclear. Two resting-state functional MRIs were collected in two clinical trials of 48 patients with TRD (clinical trial 1; 32 receiving ketamine, 16 receiving a normal saline placebo) and 48 patients with TRD and strong suicidal ideation (clinical trial 2; 24 receiving ketamine, 24 receiving midazolam), respectively. All participants underwent rs-fMRI before and 3 days after infusion. Seed-based functional connectivity (FC) was analyzed in the left/right thalamus. FCs between the bilateral thalamus and right middle frontal cortex (BA46) and between the left thalamus and left anterior paracingulate gyrus (BA8) increased among patients in the ketamine group in clinical trials 1 and 2, respectively. FCs between the right thalamus and bilateral frontal pole (BA9) and between the right thalamus and left rostral paracingulate gyrus (BA10) decreased among patients in the ketamine group in clinical trials 1 and 2, respectively. However, the associations between those FC changes and clinical symptom changes did not survive statistical significance after multiple comparison corrections. Whether ketamine-related changes in thalamocortical connectivity may be associated with ketamine's antidepressant and antisuicidal effects would need further investigation. Clinical trials registration: UMIN Clinical Trials Registry (UMIN-CTR): Registration number: UMIN000016985 and UMIN000033916.