Differential modulation of emotion processing by single dose serotonergic and noradrenergic antidepressants – a pharmaco-fMRI study

The differential effect of serotonergic and noradrenergic drugs onto emotion processing related brain activation still is not clearly characterized. Neural correlates of a pessimistic attitude towards the future have been identified previously in a similarity of brain activation during the anticipation of unknown (positive/negative 50%) and negative stimuli, but not with positive anticipation. The pessimistic activation correlated with depressiveness: the more depressed, the more resembled the activation during unknown the negative expectation. Our goal was the differentiation of this brain activation concerning noradrenergic and serotonergic modulation to find main sites of action of the two systems. We used the acute application of a SSRI and a SNARI to boost the respective neurotransmission. 20 subjects ingested a single dose of 40mg citalopram, 8mg reboxetine or placebo in a single-blind randomized crossover-study prior to fMRI. During fMRI, subjects performed a task comprising the anticipation and perception of pictures of either known (positive, negative, neutral) or unknown valence (50% positive/negative). Reboxetine increased in the direct comparison with citalopram brain activity in the mediodorsal thalamus. Citalopram modulated more prefrontal and insular areas. Other frontal and parieto-occipital areas were modulated by both drugs. These findings could have implications for future selection criteria concerning antidepressant therapy in depression.