Vagus Nerve Stimulation Modulates Inflammation in Treatment-resistant Depression Patients
Bibliographic record
Abstract
Abstract Background The role of inflammation in major depression is increasingly recognized. Vagal neurostimulation (VNS) is used for the treatment of epilepsy and major medical-refractory depression. VNS has neuropsychiatric functions and systemic anti-inflammatory activity. The objective of this study is to measure the clinical efficacy and assess the impact on the modulation of VNS in depressive patients. Materials and Methods Six patients with refractory depression were enrolled. Depression symptoms were assessed with the Montgomery-Asberg Depression Rating, and anxiety symptoms with the Hamilton Anxiety Rating Scale Scale at baseline, 12 and 24 months and also at the time of post-implantation blood harvest. To assess modulation of inflammation, plasmas were harvested prospectively before implantation of VNS (baseline) and up to after four years or more of continuous therapy. 40 soluble molecules were measured in the plasma by multiplex assays. Data were analyzed using descriptive statistics and repeated measures multivariate ANOVAs were performed. Results At time of latter blood harvest, reduction of the mean depression severity score was 59,9% and response rate was 87%. Anxiety levels were also greatly reduced. We observed a modulation of several cytokines and inflammatory proteins in TRD patients after more than 4 years of continuous therapy. IL-7, CXCL8, CCL2, CCL13, CCL17, CCL22, Fms-like tyrosine kinase-1 (Flt-1) and Vascular endothelial growth factor-C (VEGF) levels were significantly lowered, whereas levels of basic Fibroblast growth factor (bFGF) were increased (p values ranging from 0.004 to 0.02). Conclusions This exploratory study is the first to focus on long term efficacy of VNS and its consequences on inflammation biomarkers. VNS was associated with a significant and sustained clinical response in patients with major refractory depression patients. Our results suggest that VNS may modulate inflammation via an increase in the blood-brain barrier integrity and a reduction in inflammatory cells recruitment. This opens the door to new pathways involved in the treatment of refractory depression.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.003 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".