Effect of ketamine intervention on hemodynamic responses in patients with treatment-resistant depression.
Guan-jie She, Wei-chi Li, Chun-hsiang Chou, Li-Kai Cheng, Tung-Ping Su, Cheng-Ta Li, Wei-Chen Lin, Pei-Chi Tu, Shih-Jen Tsai, Ya-Mei Bai, Mu-Hong Chen, Li-Fen Chen
Scientific reports May 20, 2026 Peer reviewed DOI: 10.1038/s41598-026-51314-3 via PubMed
Summary
Ketamine infusion significantly altered hemodynamic response parameters in specific brain regions of patients with treatment-resistant depression. In a study of 45 patients, those receiving ketamine showed changes in time-to-peak and full-width at half-maximum in the bilateral olfactory cortex and right inferior parietal gyrus. Improvements in suicidal ideation were linked to changes in the thalamus and superior frontal gyrus. These findings suggest that ketamine affects brain regions involved in mood regulation and cognitive control.
Study at a glance
| Design | clinical trial |
|---|---|
| Sample size | 45 |
| Population | patients with treatment-resistant depression |
| Key finding | Ketamine significantly altered hemodynamic response parameters associated with improvements in suicidal ideation. |
Abstract
Emerging evidence shows that ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, can produce rapid anti-suicidal effects in treatment-resistant depression, yet its underlying neuropharmacological mechanisms remain elusive. The present study aimed at investigating the therapeutic effect of ketamine infusion on suicidal ideation by examining hemodynamic response changes in resting-state fMRI (rsfMRI) data. We analyzed data from clinical trials involving 45 patients with treatment-resistant depression, including either ketamine (N = 21) or midazolam (N = 24). T1-weighted images and rsfMRI data were collected before and three days after treatment. Three parameters, including response height (RH), time-to-peak (TTP), and full-width at half-maximum (FWHM), were extracted. Results showed that ketamine significantly altered TTP and FWHM in the bilateral olfactory cortex and right inferior parietal gyrus. Changes in TTP and FWHM within the thalamus and superior frontal gyrus were associated with improvements in suicidal ideation. Additionally, ketamine responders exhibited reduced TTP in the left precuneus. These findings suggest that ketamine induces region-specific HRF modulations in brain regions implicated in sensory-cognitive integration, mood regulation, and cognitive control. This supports a broader model in which ketamine's neuropharmacological effects may be understood through the lens of neurovascular coupling dynamics.