TY - JOUR
T1 - Modulation of functional networks related to the serotonin neurotransmitter system by citalopram
T2 - Evidence from a multimodal neuroimaging study
AU - Boucherie, Daphne E.
AU - Reneman, Liesbeth
AU - Booij, Jan
AU - Martins, Daniel
AU - Dipasquale, Ottavia
AU - Schrantee, Anouk
N1 - Funding Information: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Funding for this study was provided by ERA-NET PrioMed-Child (joined call of Priority Medicines for Children 40-41800-98-026). The brain-dedicated SPECT camera was funded by The Netherlands Organisation for Health Research and Development (ZonMw 91112002). AS is supported by an NWO ZonMw Veni 016.196.153. Publisher Copyright: © The Author(s) 2023.
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
KW - REACT
KW - SPECT
KW - Serotonin system
KW - citalopram
KW - functional connectivity
UR - http://www.scopus.com/inward/record.url?scp=85176725825&partnerID=8YFLogxK
U2 - https://doi.org/10.1177/02698811231211154
DO - https://doi.org/10.1177/02698811231211154
M3 - Article
C2 - 37947344
SN - 0269-8811
VL - 37
SP - 1209
EP - 1217
JO - Journal of psychopharmacology (Oxford, England)
JF - Journal of psychopharmacology (Oxford, England)
IS - 12
ER -