Introduction
depression, SSRI-induced, anxiety
DISORDERS
Selective serotonin reuptake inhibitors (SSRIs), such as citalopram, are frequently used to treat depression and anxiety disorders (While the exact mechanisms underlying the therapeutic effects of SSRIs remain contentious, the primary pharmacological mode of action entails blocking the serotonin (5-HT) transporter (5-HTT) (Our current knowledge of the effects of SSRIs on the human brain has greatly benefited from the use of non-invasive neuroimaging techniques. Particularly, the combination of functional magnetic resonance imaging (fMRI) with an acute pharmacological challenge, that is, pharmacological MRI (phMRI), has offered an unprecedented opportunity to investigate acute drug effects on brain function at the systems level, which is essential for understanding the psychopharmacological effects of drugs affecting widespread neuromodulatory systems such as 5-HT. Studies employing phMRI at rest have demonstrated that SSRIs modulate activity and connectivity both in brain regions with high 5-HTT density and in their projection areas, likely reflecting downstream effects via 5-HT (and other neurotransmitter) receptors. For example, SSRI administration has been found to alter connectivity within and with the default mode network (DMN) (Multimodal studies combining phMRI with molecular imaging have shed further light on the involvement of specific 5-HT receptors in modulating functional connectivity (FC) and SSRI-induced changes in brain function. For instance, one study found that 5-HTT availability following citalopram administration was associated with FC between the DMN and cortical regions (To this end, we conducted a multimodal study combining single-photon emission computerized tomography (SPECT) with Receptor-Enriched Analysis of functional Connectivity by Targets (REACT) (