Changes in CREB-phosphorylation during recovery from major depression

For decades psychiatrists have been looking for biological state markers measurable by easy blood test in order to follow up and predict early on treatment response in patients with major depression. In the present study we investigated whether or not measuring CREB (cAMP-response-element-binding-protein) phosphorylation in peripheral blood T lymphocytes is a state marker of treatment response. CREB is an ubiquitous key-element of intracellular signal transduction cascades and its transcriptional activity depends on phosphorylation at Ser-133. Several studies in animals demonstrated that the transcriptional activity of CREB is up-regulated by antidepressant treatment. Therefore, it has been hypothesized that antidepressant treatment exerts its therapeutic effect by this mechanism. In the present study, we investigated CREB-phosphorylation in T-lymphocytes of 20 patients before and in the end of week one and two of either psychopharmacological or psychotherapeutic treatment. After two weeks, 15 patients fulfilled the criteria of treatment response (i.e. 30% reduction in HAMD score compared to baseline), whereas five patients did not. In the end of week two, the responders showed a significant increase in CREB-phosphorylation ( P=0.018) compared to the non-responders. This was true for all patients with either treatment regimen. In conclusion, these results indicate for the first time that the increase in CREB-phosphorylation might be a molecular state marker for the response to antidepressant treatment.