Differential effects of serotonergic and noradrenergic antidepressants on cognitive flexibility, sleep and CREB-phosphorylation in depressed patients

Recently it has been hypothesized, that impaired neuroplasticity in depression causes cognitive deficits, most prominently as a decline in tasks of cognitive flexibility and fluency. There is preclinical evidence that noradrenergic and serotonergic antidepressants differ considerably in their capacity to increase the activity of the transcription factor CREB, which is essential for positive effects on cellular and synaptic plasticity. But to date it is unclear if the activation of pro-plastic signaltransduction cascades by antidepressants is in fact relevant for the remission of cognitive deficits in patients. We adressed this issue by treating depressed patients exclusively with SSRIs (citalopram), NRIs (reboxetine) or psychotherapy. We tested cognitve performance within the first 4 weeks of treatment. Furthermore we investigated changes in slow wave activity during sleep, presumably reflecting plasticity processes in the cortical circuitry, in the course of treatment. We also probed CREB-phosphorylation in patients T-lymphocytes previously demonstrated to be a suitable peripheral cellular model. We will present preliminary data from 30 patients, with 10 patients in each treatment group. Results suggest that cognitive performance is differentially modulated by antidepressants.