Modulation of functional networks related to the serotonin neurotransmitter system by citalopram: Evidence from a multimodal neuroimaging study.
J Psychopharmacol
; 37(12): 1209-1217, 2023 Dec.
Article
em En
| MEDLINE
| ID: mdl-37947344
ABSTRACT
BACKGROUND:
Selective serotonin reuptake inhibitors (SSRIs) potentiate serotonergic neurotransmission by blocking the serotonin transporter (5-HTT), but the functional brain response to SSRIs involves neural circuits beyond regions with high 5-HTT expression. Currently, it is unclear whether and how changes in 5-HTT availability after SSRI administration modulate brain function of key serotoninergic circuits, including those characterized by high availability of the serotonin 1A receptor (5-HT1AR).AIM:
We investigated the association between 5-HTT availability and 5-HTT- and 5-HT1AR-enriched functional connectivity (FC) after an acute citalopram challenge.METHODS:
We analyzed multimodal data from a dose-response, placebo-controlled, double-blind study, in which 45 healthy women were randomized into three groups receiving placebo, a low (4 mg), or high (16 mg) oral dose of citalopram. Receptor-Enhanced Analysis of functional Connectivity by Targets was used to estimate 5-HTT- and 5-HT1AR-enriched FC from resting-state and task-based fMRI. 5-HTT availability was determined using [123I]FP-CIT single-photon emission computerized tomography.RESULTS:
5-HTT availability was negatively correlated with resting-state 5-HTT-enriched FC, and with task-dependent 5-HT1AR-enriched FC. Our exploratory analyses revealed lower 5-HT1AR-enriched FC in the low-dose group compared to the high-dose group at rest and the placebo group during the emotional face-matching task.CONCLUSIONS:
Taken together, our findings provide evidence for differential links between 5-HTT availability and brain function within 5-HTT and 5-HT1AR pathways and in context- and dose-dependent manner. As such, they support a potential pivotal role of the 5-HT1AR in the effects of citalopram on the brain and add to its potential as a therapeutic avenue for mood and anxiety disturbances.Palavras-chave
Texto completo:
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Bases de dados:
MEDLINE
Assunto principal:
Citalopram
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Inibidores Seletivos de Recaptação de Serotonina
Limite:
Female
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Humans
Idioma:
En
Revista:
J Psychopharmacol
Assunto da revista:
PSICOFARMACOLOGIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Holanda