Brain functional network correlates and predictors of the perioperative antidepressant effect of esketamine in breast cancer patients: a double-blind randomized controlled trial using resting-state fMRI and graph theory.
Huimin Zhu, Qingfeng Wei, Shuang Xu, Yunwei Sun, Xuesheng Liu, Jiajia Zhu, Yongqiang Yu
Translational Psychiatry March 6, 2026 DOI: 10.1038/s41398-026-03929-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 35 |
| Population | Breast cancer patients with preoperative depressive symptoms |
| Intervention | Esketamine |
| Dose | 0.25 mg·kg⁻¹ |
| Duration | Administered over the initial 40 min of anesthesia; follow-up at postoperative day 1 |
| Topics | Depression Ketamine Esketamine |
| Keywords | Brain Humans Breast neoplasms Postoperative complications Antidepressive agents Magnetic resonance imaging Treatment outcome Double-blind method Adult Middle aged Female |
| Citations | 1 |
| Key findings | Intraoperative esketamine increased degree centrality of the left inferior frontal gyrus (opercular part) from baseline to postoperative day 1, which was related to improvement in depressive symptoms, whereas the placebo group showed no significant change. Baseline functional network measures were associated with short- and long-term antidepressant response to esketamine. |
Abstract
Postoperative depression adversely influences breast cancer patients' clinical outcomes. Our prior study demonstrated that intraoperative esketamine ameliorated postoperative depression in breast cancer patients, yet the underlying neural mechanism remains incompletely understood. We performed a double-blind randomized controlled trial in 35 breast cancer patients with preoperative depressive symptoms, who were randomly given intraoperative esketamine 0.25 mg·kg⁻¹ (n = 18) or saline placebo (n = 17) over the initial 40 min of anesthesia. Resting-state functional magnetic resonance imaging data were collected at preoperative baseline and postoperative day 1 follow-up to calculate brain functional network measures. In contrast to no significant change in the placebo group, the esketamine group showed increased degree centrality of the left inferior frontal gyrus, opercular part from baseline to follow-up, which was related to improvement in depressive symptoms. Additionally, we found significant associations of baseline network measures at the global, nodal, and edge levels with short-term and long-term improvements in depressive symptoms following esketamine administration. These findings may not only provide novel insights into the neural mechanism by which esketamine exerts its antidepressant efficacy during the perioperative period, but also highlight the prospect of functional network measures as useful predictors of antidepressant response to esketamine in patients with breast cancer.
Comparable studies
Other randomized controlled trials on esketamine for depression, most cited first.