A pilot study of serotonin-1A receptor genotypes and rapid eye movement sleep sensitivity to serotonergic/cholinergic imbalance in humans: a pharmacological model of depression
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Résumé
RATIONALE: The serotonergic and cholinergic systems are jointly involved in regulating sleep but this system is theorized to be disturbed in depressed individuals. We previously reported that cholinergic and serotonergic agents induce sleep changes partially consistent with monoamine models of sleep disturbances in depression. One potential cause of disturbed neurotransmission is genetic predisposition. The G(-1019) allele of the serotonin-1A (5-HT1A) receptor promoter region predicts an increased risk for depression compared to the wild-type C(-1019) allele. OBJECTIVE: The goal of this study was to investigate how serotonin-1A receptor genotypes mediate sleep sensitivity to pharmacological probes modeling the serotonergic/cholinergic imbalance of depression. METHODS: Seventeen healthy female participants homozygous for either C (n=11) or G (n=6) alleles aged 18-27 years were tested on four nonconsecutive nights. Participants were given galantamine (an anti-acetylcholinesterase), buspirone (a serotonergic agonist), both drugs together, or placebos before sleeping. RESULTS: As reported previously, buspirone significantly increased rapid eye movement (REM) latency (P<0.001), as well as awakenings, percentage of time spent awake, and percentage of time asleep spent in stage N1 (P<0.019). Galantamine increased awakenings, percentage of time spent awake, percentage of time asleep spent in stage N1, and percentage of time asleep spent in REM, and decreased REM latency and percentage of time asleep spent in stage N3 (P<0.019). Galantamine plus buspirone given together disrupted sleep more than either drug alone, lowering sleep efficiency and percentage of time asleep spent in stage N3 and increasing awakenings, percentage of time spent awake, and percentage of time asleep spent in stage N1 (P<0.019). There was no main effect of genotype nor was there a significant multivariate interaction between genotype and drug condition. CONCLUSION: These findings are partially consistent with the literature about sleep in depression, notably short REM latency, higher percentage of total sleep time spent in REM, lower percentage of time asleep spent in stage N3, and increased sleep fragmentation. The C/G mutation in the serotonin-1A receptor promoter region does not appear to cause noticeable differences in the sleep patterns of a relatively small sample of healthy young females. Future studies with larger sample sizes are required.
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Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| 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) | 0,000 | 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 découle