O8.4. CORTICAL DOPAMINE RELEASE IN RESPONSE TO A COGNITIVE CHALLENGE: PRELIMINARY RESULTS IN FIRST EPISODE PSYCHOSIS AND CLINICAL HIGH RISK
Notice bibliographique
Résumé
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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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».