Serotonin (5-HT) is thought to be critical for affect regulation in the brain and many antidepressants are thought to primarily work by altering 5-HT levels. However there has not been a validated means of directly imaging of endogenous 5-HT levels in humans. The main aims of this project are to image the effect of Citalopram on brain endogenous 5-HT levels and to determine the relationship between brain 5-HT and affect regulation.

Thirteen healthy volunteers (mean age 50.9yrs, range 35–63) underwent two Positron Emission Tomography (PET) scans with [¹¹C]-CUMI, a highly selective 5-HT_1A agonist radioligand. Subjects received either a slow intravenous infusion of citalopram 10mg or saline starting 45 minutes before each PET scan in a randomized design. All subjects had a functional MRI emotion processing task (block design) known to activate the amygdala on a separate day.

The citalopram infusion induced 6–11% increases in [¹¹C]-CUMI binding potential in anterior cingulate, insula and cortical brain regions (p<0.05 corrected for repeated measures).

BOLD response to fearful vs neutral faces in the left amygdala inversely correlated with baseline dorsal raphe BP (Pearson r² =−0.90, p<0.001) and directly correlated with dorsal raphe BP changes (r²=0.51, p=0.07).

The increase in [¹¹C]CUMI-101 availability would be consistent with a decrease in endogenous 5-HT availability in certain terminal regions. The relationship between brain emotion processing and [¹¹C]-CUMI binding in the raphe indicates the 5-HT levels at presynaptic receptors regulate emotional processing and suggests presynaptic 5-HT as a treatment target for affective disorders.