# Video research insert: Dopamine Hypothesis of Schizophrenia

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

Dopamine is relevant to psychotic symptoms, and antipsychotic treatment has demonstrated clinical effects. The specific hypothesis reviewed here makes a stronger claim: excess mesolimbic dopamine is the primary cause of psychotic symptoms across unselected schizophrenia. Imaging often finds its strongest abnormality in associative striatum, and prospective transition studies remain associations. Small treatment-resistance studies suggest heterogeneity, but a larger multicentre study did not reproduce a clear dopamine classifier. A muscarinic trial improved symptoms without establishing whether dopamine mediated that benefit. Our Gamma rating concerns the exact primary-cause claim. The strict treatment-mechanism subclaim is also limited by registration and mediator information not verified in this audit. A decisive trial would measure target engagement and a prespecified symptom trajectory with credible controls.

## 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

- 2000: [PMID 10739409](https://pubmed.ncbi.nlm.nih.gov/10739409/) — Double-blind PET/treatment study relates D2 occupancy to response and adverse effects.
- 2000: [PMID 10884434](https://pubmed.ncbi.nlm.nih.gov/10884434/) — Depletion imaging tests endogenous baseline occupancy differences.
- 2010: [PMID 20194823](https://pubmed.ncbi.nlm.nih.gov/20194823/) — Regional depletion study localizes a stronger associative than limbic signal.
- 2011: [PMID 21768612](https://pubmed.ncbi.nlm.nih.gov/21768612/) — Prospective high-risk PET study tests temporal association with transition.
- 2012: [PMID 23034655](https://pubmed.ncbi.nlm.nih.gov/23034655/) — Small responder/TRS comparison suggests heterogeneity.
- 2021: [PMID 32910150](https://pubmed.ncbi.nlm.nih.gov/32910150/) — Multicentre STRATA challenges a settled dopamine response classifier.
- 2024: [PMID 38691387](https://pubmed.ncbi.nlm.nih.gov/38691387/) — Registered muscarinic trial improves symptoms without resolving dopamine mediation.