Tackling the effect of duloxetine on brain function in mood specific emotional processing in healthy volunteers: An fMRI study bridging pharmacotherapeutical and cognitive psychological approaches to depression

Enhancement of serotonin and/or norepinephrine neurotransmission is the main approach in the pharmacological treatment of depressive disorder. However, the precise neurobiological mechanisms on the system level are not fully understood yet. Our starting point is that cognitive psychological approaches emphasise the role of negative biases in perception, attention and memory in the development and maintenance of depressive disorder.
In an attempt to bridge the pharmacological and the cognitive psychological approach, a recent study by Harmer and colleagues (2004) in healthy volunteers has shown that administration (for 7 days) of a selective serotonin reuptake inhibitor (SSRI, citalopram) as well as of a selective norepinephrine reuptake inhibitor (reboxetine) had similar effects in reducing the negative biases of emotional stimuli. In particular, the link between depression and bias for memory appears to be of most importance: A depressed individual retrieves preferentially negative memories, which in turn maintains or aggravates depressive symptomatology, resulting in a vicious cycle. Moreover, negative retrieval reinforces an interpretation bias potentially affecting the formation of new memories by preferring negative information.

The current study wants extend this research and to further elucidate the mechanisms of action at a neuronal level of the new ‘dual action’ antidepressant duloxetine in the modulation of negative biases in information processing of the emotional stimuli in connection with depressive mood with a special emphasis on memory. Like Harmer and colleagues, we will investigate these mechanisms in healthy volunteers and not in patients with a depression. The use of healthy volunteers enables us to shed light on the direct action of the antidepressant unconfounded by symptom remission or mood improvement that may be seen in patients.

The main hyothesis of the experiments is that a dual action antidepressant (duloxetine) modulates functions in specific brain areas involved in the processing bias of emotional stimuli in the context of neutral versus depressed mood.

- after 14 days of use of duloxetine

- after 14 days of use of placabo

This study will be a double-blind, placebo-controlled, cross-over study. Volunteers will be randomly assigned to one of two treatment sequences. Each volunteer will receive the dual action antidepressant duloxetine for 14 days and placebo for 14 days with an interval of 14 days between each treatment.