Triple-network model-based graph theory analysis of the effectiveness of low-dose ketamine in patients with treatment-resistant depression: two resting-state functional MRI clinical trials.
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
The British journal of psychiatry : the journal of mental science April 2, 2025 DOI: 10.1192/bjp.2025.14 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Secondary analysis of two randomized controlled trials Peer reviewed |
|---|---|
| Population | Patients with treatment-resistant depression; one trial included those with pronounced suicidal symptoms |
| Interventions | ketamine normal saline midazolam |
| Dose | 0.05 mg/kg ketamine, 0.045 mg/kg midazolam |
| Duration | Single infusion, with imaging pre and post infusion at Day 3 |
| Topics | Depression Ketamine Esketamine |
| Keywords | Triple-network model Graph theory Resting-state functional connectivity Ketamine therapy Brain connectivity Neuroscience research Mental health treatment |
| Citations | 2 |
| Key findings | Low-dose ketamine altered functional connectivity measures in the default mode, salience, and frontoparietal networks in patients with treatment-resistant depression. |
Abstract
Evidence suggests the crucial role of dysfunctional default mode (DMN), salience and frontoparietal (FPN) networks, collectively termed the triple network model, in the pathophysiology of treatment-resistant depression (TRD). Using the graph theory- and seed-based functional connectivity analyses, we attempted to elucidate the role of low-dose ketamine in the triple networks, namely the DMN, salience and FPN. Resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) data derived from two previous clinical trials of a single, low-dose ketamine infusion were analysed. In clinical trial 1 (Trial 1), patients with TRD were randomised to either a ketamine or normal saline group, while in clinical trial 2 (Trial 2) those patients with TRD and pronounced suicidal symptoms received a single infusion of either 0.05 mg/kg ketamine or 0.045 mg/kg midazolam. All participants underwent rs-fcMRI pre and post infusion at Day 3. Both graph theory- and seed-based functional connectivity analyses were performed independently. Trial 1 demonstrated significant group-by-time effects on the degree centrality and cluster coefficient in the right posterior cingulate cortex (PCC) cortex ventral 23a and b (DMN) and the cluster coefficient in the right supramarginal gyrus perisylvian language (salience). Trial 2 found a significant group-by-time effect on the characteristic path length in the left PCC 7Am (DMN). In addition, both ketamine and normal saline infusions exerted a time effect on the cluster coefficient in the right dorsolateral prefrontal cortex a9-46v (FPN) in Trial 1. These findings may support the utility of the triple-network model in elucidating ketamine's antidepressant effect. Alterations in DMN, salience and FPN function may underlie this effect.
Comparable studies
Other randomized controlled trials on ketamine for depression, most cited first.