203. Nigral Stress-Induced Dopamine Release in Clinical High Risk and Antipsychotic-Naive Schizophrenia
Bibliographic record
Abstract
Background: Dopamine (DA) synthesis capacity and release are elevated in schizophrenia (SCZ) and its putative prodrome, the clinical high risk state (CHR). Striatal DA results from the activity of midbrain DA neurons projecting mainly from the substantia nigra (SN). Elevated stress-induced DA release in SCZ and CHR was observed in the striatum, however whether it is also elevated in the SN is unclear. The current study aims to determine whether nigral DA release in response to a validated stress task is altered in CHR and in antipsychotic-naive SCZ. Further, we explore how DA release in the SN and striatum might be related. Methods: 24 CHR subjects, 9 antipsychotic-naive SCZ and 25 healthy volunteers (HV) underwent two positron emission tomography (PET) scans using the DA D2/3 agonist radiotracer, [11C]-(+)-PHNO, which allows simultaneous investigations of DA in the SN and striatum. Psychosocial stress-induced DA release was estimated as the percentage differences in BPND (%[11C]-(+)-PHNO displacement) between stress and sensory-motor control sessions. Results: We observed a significant group by sessions interaction on [11C]-(+)-PHNO BPND in the SN (F = 6.896, P = .002). The SCZ showed a 25.90% [11C]-(+)-PHNO binding change change in nigral [11C]-(+)-PHNO displacement, while HV showed -10.94% and CHR exhibited an intermediate response [11C]-(+)-PHNO binding change (−1.13%). Only among the CHR subjects, we found a positive trend of association between [11C]-(+)-PHNO binding changes displacement in the SN and the whole striatum (r = .382, P = .072). Conclusion: Our findings suggest a sensitized nigral DA response to stress in antipsychotic-naive SCZ. The unique trend association between nigral and striatal [11C]-(+)-PHNO binding changes, and a differential nigrostriatal DA pathway in CHR, which may suggest a stage specific biomarker warrants further investigation to confirm.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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 source (direct Gemma or distilled Codex), 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".