How Antidepressants Work: SSRI Treatment Induces Adaptive Changes in Brain 5-HT phMRI Responses

Introduction Serotonin specific reuptake inhibitors (SSRIs), which are used to treat depression, typically require 10-14 days of administration before clinically beneficial effects are seen. The biological mechanisms that mediate antidepressant action are not well understood. Citalopram, a standard SSRI antidepressant, can be administered intravenously and its effects on the BOLD response assessed using phMRI. Acute 5-HT challenge as detected by phMRI has highlighted several brain areas enriched with 5-HT reuptake sites, which have also been implicated in the development and treatment of depression (McKie et al., 2005; Anderson et al., 2008). The therapeutic effect of SSRIs may be the result of adaptive changes in the 5-HT system to sustained reuptake inhibition. We hypothesised that chronic SSRI usage may down regulate raphe nuclei 5-HT1a and 5-HT2c receptor expression and enhance 5-HT1 signalling in post synaptic areas mediating the delayed therapeutic effect. Using citalopram challenge phMRI we examined the BOLD response to the acute and sub-chronic effects of SSRIs in order to explore adaptive changes to the 5-HT system.