Spatiotemporal brain activation pattern following acute citalopram challenge is dose dependent and associated with neuroticism: A human phMRI study

Background: The initial effects of selective serotonin reuptake inhibitors (SSRIs) in the human living brain are poorly understood. We carried out a 3T resting state fMRI study with pharmacological challenge to determine the brain activation changes over time following different dosages of citalopram. Methods: During the study, 7.5 mg i.v. citalopram was administered to 32 healthy subjects. In addition, 11.25 mg citalopram was administered to a subset of 9 subjects to investigate the dose-response. Associations with neuroticism (assessed by the NEO PI-R) of the emerging brain activation to citalopram was also investigated. Results: Citalopram challenge evoked significant activation in brain regions that are part of the default mode network, the visual network and the sensorimotor network, extending to the thalamus, and midbrain. Most effects appeared to be dose-dependent and this was statistically significant in the middle cingulate gyrus. Individual citalopram-induced brain responses were positively correlated with neuroticism scores and its sub-scales in specific brain areas; anxiety subscale scores in thalamus and midbrain and self-consciousness scores in middle cingulate gyrus. There were no sex differences. Limitations: We investigated only healthy subjects and we used a relatively low sample size in the 11.25 mg citalopram analysis. Discussion: Our results suggest that SSRIs acutely induce an increased arousal-like state of distributed cortical and subcortical systems that is mediated by enhanced serotonin neurotransmission according to levels of neuroticism and underpins trait sensitivity to environmental stimuli and stressors. Studies in depression are needed to determine how therapeutic effects eventually emerge. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'.