ArticleClinical neuropsychiatry2025
Stratifying the Inflamed Endotype in Difficult-to-Treat Depression: A Roadmap from Biomarkers to Precision Immunopsychiatry.
Article in Clinical neuropsychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
3 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Multilevel Mechanisms and Clinical Efficacy of Psilocybin in Depression Treatment: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- Mitochondrial control of blood-brain barrier homeostasis in neuroinflammatory psychiatric disorders.Frontiers in molecular neuroscience · 2026Review
- Imbalance of the Brain-Gut-Microbiota Axis in Major Depressive Disorder: From Pathogenesis to Clinical Translation.Neuropsychiatric disease and treatment · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Difficult-to-treat depression (DTD) extends beyond pharmacological non-response to encompass persistent symptoms, disability, and functional impairment despite optimal therapeutic strategies. This opinion advances a paradigm-shifting thesis: a biologically distinct inflammatory endotype exists within DTD, characterized by low-grade systemic inflammation (hs-CRP ≥3 mg/L), where treatment failure reflects a fundamental mechanistic mismatch between the pathogenic driver (neuroinflammation) and conventional monoaminergic interventions. We propose a precision stratification workflow: screen with hs-CRP, confirm and phenotype using a parsimonious cytokine panel (IL-6, TNF-α, IL-1β), and align interventions to underlying biology. Therapeutic options include targeted anti-inflammatory agents, neuromodulation, psychotherapy, lifestyle modifications, and digital monitoring. Assessment should prioritize patient-centered outcomes: functioning, quality of life, and cognition alongside symptom reduction. We outline pragmatic implementation within phased-care and public health systems, emphasizing equitable biomarker access and biomarker-enriched clinical trials. Reframing DTD through neuroinflammation transforms clinical heterogeneity from an obstacle into an opportunity: biomarker-guided precision care that matches mechanism to intervention, improving outcomes for patients whose depression has proven refractory to standard approaches.
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.