Stress‐induced cortical dopamine response is altered in subjects at clinical high risk for psychosis using cannabis
Bibliographic record
Abstract
Abstract Stress and cannabis use are risk factors for the development of psychosis. We have previously shown that subjects at clinical high risk for psychosis (CHR) exhibit a higher striatal dopamine response to stress compared with healthy volunteers (HV), with chronic cannabis use blunting this response. However, it is unknown if this abnormal dopamine response extends to the prefrontal cortex (PFC). Here, we investigated dorsolateral PFC (dlPFC) and medial PFC (mPFC) dopamine release using [ 11 C]FLB457 positron emission tomography (PET) and a validated stress task. Thirty‐three participants completed two PET scans (14 CHR without cannabis use, eight CHR regular cannabis users [CHR‐CUs] and 11 HV) while performing a Sensory Motor Control Task (control scan) and the Montreal Imaging Stress Task (stress scan). Stress‐induced dopamine release (Δ BP ND ) was defined as percent change in D 2/3 receptor binding potential between both scans using a novel correction for injected mass of [ 11 C]FLB457. Δ BP ND was significantly different between groups in mPFC ( F (2,30) = 5.40, .010), with CHR‐CUs exhibiting lower Δ BP ND compared with CHR (.008). Similarly, salivary cortisol response (Δ AUC I ) was significantly lower in CHR‐CU compared with CHR ( F (2,29) = 5.08, .013; post hoc .018) and positively associated with Δ BP ND . Furthermore, CHR‐CUs had higher attenuated psychotic symptoms than CHR following the stress task, which were negatively associated with Δ BP ND . Length of cannabis use was negatively associated with Δ BP ND in mPFC when controlling for current cannabis use. Given the global trend to legalize cannabis, this study is important as it highlights the effects of regular cannabis use on cortical dopamine function in high‐risk youth.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".