O8.4. CORTICAL DOPAMINE RELEASE IN RESPONSE TO A COGNITIVE CHALLENGE: PRELIMINARY RESULTS IN FIRST EPISODE PSYCHOSIS AND CLINICAL HIGH RISK
Bibliographic record
Abstract
Evidence from several lines of research suggest decreased dopamine (DA) release in the prefrontal cortex (PFC) as the neural correlate of cognitive deficits in schizophrenia (SCZ). Impaired executive functions, such as attention and working memory, are key features of the disease and are strong predictors of later functional status. However, there are currently no in-vivo studies examining cortical DA function in response to a cognitive task in putative prodromal stages of SCZ, despite the large amount of evidence pointing to the cortical hypodopaminergia hypothesis. We aim to investigate differences in cognitive task-induced cortical DA function indexed as DA release at the first episode psychosis (FEP) stage of the illness and then further in the clinical high risk (CHR) for psychosis stage using PET imaging with [11C]-FLB-457 radiotracer. In the first previously published study, we examined DA release between healthy controls (HC) and FEP patients and in the second study between HC and CHR participants. Study 1: 13 HC and 13 FEP, recruited from the Center for Addiction and Mental Health (CAMH). Study 2: 14 CHR and 15 HC and 14 CHR, recruited from the Focus on Youth Psychosis Prevention clinic at CAMH. HC participants for both studies were recruited from the community and had no current or past DSM-IV Axis I diagnosis and no family history of psychotic disorders. All FEP and CHR had no concurrent axis I disorder. The Repeatable Battery for the Assessment of Neuropsychological Status and Wisconsin Card Sorting Task (WCST) was administered to assess executive functions such as attention and working memory. Each participant underwent a 90-minute dual PET scan procedure using a high-resolution PET-CT during which they performed 6 trials of the Sensory Motor Control Task and the WCST. The main measure of interest is the difference in cortical DA release between groups, assessed by quantifying the displacement of the [11C]-FLB-457 radiotracer (ΔBPND) between the two scans in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) between groups in each study. Each participant also completed an MRI scan for anatomical delineation. Study 1: Significant differences in the cognitive task induced ΔBPND in ACC (HC=4.40 ± 6.00; FEP=-11.48 ± 15.08; t=3.52; p=0.003) and a trend level difference in ΔBPND in DLPFC (HC=-0.58 ± 8.45; FEP=-7.79± 11.28; t= 1.84; p=0.079). Study 2: No significant differences in the cognitive task induced ΔBPND in ACC (HC=4.33 ± 15.65; CHR=-2.10 ± 14.21; t=3.92; p=0.698) or DLPFC (HC=-2.47± 9.88; CHR=0.77± 14.27; t=0.71; p=0.486). Data from these studies provide for the first time, in-vivo evidence for impaired task induced DA release in the ACC and DLPFC in patients at FEP. The present results provide support for the cortical hypodopaminergia hypothesis of cognitive symptoms in SCZ. Further, because these DA abnormalities are not present in CHR phase, perhaps they develop once further down the illness progression. These findings can be used in identifying biological risk factors of SCZ and aid in developing preventative treatment measures.
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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 | 0.001 | 0.001 |
| 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".