Abstract
AbstractSelective serotonin reuptake inhibitors (SSRIs) potentiate serotonergic neurotransmission primarily 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 serotonin 1A receptors (5-HT1AR). Here, we investigated the association between 5-HTT availability and 5-HTT- and 5-HT1AR-enriched functional connectivity (FC) after an acute citalopram challenge. 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 fMRI and task-based fMRI data. 5-HTT availability was determined using [123I]FP-CIT single-photon emission computerized tomography. 5-HTT availability was negatively correlated with resting-state 5-HTT-enriched FC, and with task-dependent 5-HT1AR-enriched FC. We also found lower 5-HT1AR-enriched FC in the low dose group compared to the high dose group at rest and to the placebo group during the task. Our findings provide evidence for differential links between 5-HTT availability and brain function within 5-HTT and 5-HT1AR pathways that are likely context- and dose-dependent, supporting a potential pivotal role of the 5-HT1AR in the effects of citalopram on the human brain and adding to the interest in this target as a potential therapeutic avenue for mood and anxiety disturbances.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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