Molecular Abnormalities in Postmortem Brains of Subjects with Mood Disorders
Notice bibliographique
Résumé
Biochemical and structural abnormalities have been reported in postmortem brain tissue from patients with mood disorders. Studies of the molecular pharmacology of drugs used in the treatment of mood disorders have led to a reinterpretation of earlier models of neuropathology in these diseases. Noradrenergic and serotonergic hypotheses have been expanded to include postsynaptic intracellular signal transduction pathways, regulation of gene expression, and synaptic plasticity. Because much of this evidence was obtained from postmortem brain, the experiments in this study also used postmortem tissue to examine the neuropathology of mood disorders. Human postmortem brain tissue was obtained from the Stanley Consortium Neuropathology Foundation and consisted of pieces of temporal and occipital cortex, and slices of prefrontal cortex and hippocampus from patients with bipolar affective disorder (BD), major depressive disorder (MDD), schizophrenia (SCZ) and controls (N = 15 per group). Components of the cAMP system were examined, as were potential target transcription and neurotrophic factors. Morphological consequences arising from altered cAMP signalling such as sprouting and DNA fragmentation were also investigated. There was a trend towards blunted temporal cortex adenylyl cyclase activity in subjects with mood disorders, and decreased occipital cortex Gas in lithium-treated BD subjects. Temporal cortex CREB level~ were decreased in antidepressant-untreated MDD subjects compared to controls, and normal in those subjects treated by antidepressants at the time of death. Temporal cortex CREB levels were decreased in BD patients treated with anticonvulsants relative to those not treated by anticonvulsants at the time of death. When assessing the effect of suicide on cAMP signalling, subjects who died as a result of suicide had lower temporal cortex CREB levels and CRE-binding than subjects who died of other causes. This effect was most evident in the MDD group. In hippocampus, BDNF levels were increased in subjects treated by antidepressants compared to subjects not treated by these medications at the time of death. This finding was more pronounced in the MDD group. Hippocampal studies also showed that BD subjects had increased mossy fibre staining relative to controls and other diagnoses, suggesting increased sprouting of the dentate gyrus axons. These postmortem findings are consistent with recent animal and cell models of antidepressant and mood stabilizer pharmacology. The changes in post-receptor signalling and hippocampal sprouting are also consistent with current conceptualizations of the neurobiology of mood disorders. These studies support the use of postmortem brain tissue as a clinically relevant research model, and add to the growing literature elucidating the pathophysiology of mood disorders and the molecular pharmacology of their treatments.
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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 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 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 | 0,000 | 0,000 |
| 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 ».