# Video research insert: Inflammatory Depression Hypothesis

Draft narration and storyboard; no rendered video is claimed. Intended insert: roughly 60–90 seconds, depending on delivery.

Inflammation and depression are associated, and sustained therapeutic interferon exposure can precipitate a depressive syndrome in a defined setting. That does not validate every proposed high-CRP subtype of ordinary major depression. Original trial methods matter. The infliximab and MINDEP trials were null overall; their favorable CRP subgroups were exploratory. A prospectively stratified celecoxib trial did not establish the expected benefit. Acute inflammatory challenges measure changes over hours and cannot be equated with sustained major depression. Our Gamma rating preserves plausible amplification while leaving subgroup causality unresolved. INSTA-MD is an identifiable test of inflammation-targeted treatment, but the registry status is stale and no outcome is assumed. The next result must establish a prespecified interaction, target engagement and durable clinical benefit.

## Visual sequence

1. Show the exact registered hypothesis and its overall HSEF level.
2. Animate the selected publication milestones from research-timeline.json; label clinical trials, observational studies and models distinctly.
3. Contrast the strongest source result with its scope or endpoint limitation.
4. End on the registered boundary experiment, with primary-source links on screen.

Use newly authored schematic graphics. Do not turn Consensus meters into causal confidence graphics. If depicting a study endpoint, show its actual hierarchy; do not animate an exploratory subgroup as a confirmed treatment effect.

## Source cues

- 2001: [PMID 11274622](https://pubmed.ncbi.nlm.nih.gov/11274622/) — Antidepressant prophylaxis during prolonged interferon exposure tests clinically diagnosed depression.
- 2013: [PMID 22945416](https://pubmed.ncbi.nlm.nih.gov/22945416/) — Overall infliximab trial null with exploratory inflammation-related findings.
- 2021: [PMID 33504955](https://pubmed.ncbi.nlm.nih.gov/33504955/) — MINDEP overall null and exploratory higher-CRP subgroup.
- 2022: [PMID 36103181](https://pubmed.ncbi.nlm.nih.gov/36103181/) — Multicentre MinoTRD trial retains a null primary clinical result.
- 2024: [PMID 37635396](https://pubmed.ncbi.nlm.nih.gov/37635396/) — Prospectively stratified PREDDICT report challenges automatic CRP-subtype benefit.
- 2025: [PMID 40264292](https://pubmed.ncbi.nlm.nih.gov/40264292/) — Acute challenge tests anhedonia and time-dependent mood response.
- 2025: [PMID 40668551](https://pubmed.ncbi.nlm.nih.gov/40668551/) — Older-insomnia challenge tests transient mood effects, excluding recent MDD.