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Background <p>Studies have demonstrated that subanesthetic-dose ketamine may modulate the functioning of specific depression-related brain regions, particularly the anterior cingulate cortex and prefrontal cortex. However, how subanesthetic-dose ketamine alters the global and regional graph theory metrics of resting-state functional connectivity in patients with treatment-resistant depression (TRD) and strong suicidal symptoms remains unclear.</p> Methods <p>We conducted a randomized, double-blinded, resting-state functional magnetic resonance imaging clinical trial in patients with TRD and strong suicidal symptoms. These patients received either subanesthetic-dose ketamine (0.5&#xa0;mg/kg, <i>n</i> = 21) or midazolam (0.045&#xa0;mg/kg, <i>n</i> = 22). Neuroimaging was performed before infusion and on day 3 after infusion. A graph theory analysis was conducted to calculate global and regional metrics after infusion.</p> Results <p>Compared with the midazolam group, the ketamine group exhibited a substantially lower mean global path length after infusion. Specifically, in patients who received subanesthetic-dose ketamine treatment, the regional path lengths were decreased in key depression-related brain regions such as the anterior cingulate cortex, posterior cingulate cortex, supplementary motor area, superior parietal lobule, and superior frontal gyrus.</p> Discussion <p>Decreased global and regional path lengths suggest improved network integration following subanesthetic-dose ketamine treatment in patients with TRD and strong suicidal symptoms. Further studies are required to validate our findings.</p>

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Shorter to be effective: subanesthetic-dose ketamine infusion reduces the global and regional path length of brain functional connectivity in patients with treatment-resistant depression and suicidal ideation

  • 期刊论文

  • 发表日期：

    2026年5月22日

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  • Wei-Chen Lin,
  • Li-Kai Cheng,
  • Tung-Ping Su,
  • Li-Fen Chen,
  • Pei-Chi Tu,
  • Cheng-Ta Li,
  • Ya-Mei Bai,
  • Shih-Jen Tsai,
  • Mu-Hong Chen

摘要

Background

Studies have demonstrated that subanesthetic-dose ketamine may modulate the functioning of specific depression-related brain regions, particularly the anterior cingulate cortex and prefrontal cortex. However, how subanesthetic-dose ketamine alters the global and regional graph theory metrics of resting-state functional connectivity in patients with treatment-resistant depression (TRD) and strong suicidal symptoms remains unclear.

Methods

We conducted a randomized, double-blinded, resting-state functional magnetic resonance imaging clinical trial in patients with TRD and strong suicidal symptoms. These patients received either subanesthetic-dose ketamine (0.5 mg/kg, n = 21) or midazolam (0.045 mg/kg, n = 22). Neuroimaging was performed before infusion and on day 3 after infusion. A graph theory analysis was conducted to calculate global and regional metrics after infusion.

Results

Compared with the midazolam group, the ketamine group exhibited a substantially lower mean global path length after infusion. Specifically, in patients who received subanesthetic-dose ketamine treatment, the regional path lengths were decreased in key depression-related brain regions such as the anterior cingulate cortex, posterior cingulate cortex, supplementary motor area, superior parietal lobule, and superior frontal gyrus.

Discussion

Decreased global and regional path lengths suggest improved network integration following subanesthetic-dose ketamine treatment in patients with TRD and strong suicidal symptoms. Further studies are required to validate our findings.