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Objective´ The molecules related With the intracellular signal transduction system are one of the main targets for the mode of mechanisms of antidepressant treatment m depressive patients In vivo and In vitro studies have provided the evidence that the transcription factor, CREB (c-AMP response element binding protein) is the key mediator of the therapeutic response to antidepressants we investigated the relationship between the treatment response to fluoxetine for 6 weeks and the change of CREB immunoreactivity in peripheral T lymphocyte Methods CREB-expression and phosphorylation were quantified via western blot, and binding activity between transcription factor and CRE-oligonucleotide via electrophoretic mobility shift assay (EMSA) m nuclear extracts from 14 normal controls and 31 depressed patients at 0 and 6th week during fluoxetine treatment (20 mg/day) Responder was defined as the 250% of reduction or ≤7 of HAM-D score. We compared the changes of CREB during 6 weeks of fluoxetine treatment between drug responders and non-responders using SPSSll.0. Results : After six weeks of treatment with fluoxetine, the drug responders showed a significant increase in CREB (p=0.024 by t-test) and p-CREB (p=0.045 by Mann-Whitney U test) compared with the non-responders, The change of CREB immunoreactivity was positively correlated with the change of p-CREB (r=0.770, p=0.000 by Spearman´s rho), and the change of p-CREB was also positively correlated with CRE-DNA binding (r=0.753, p=0.000 by Spearman´s rho) Conclusion These results suggest that CREB response in penpherallymphocyte may reflect and mediate the response to antidepressant treatment m depressed patients. (Korean J Psychopharmacol 2004;15(4):440-448)
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