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.