말초 T 림프구 내의 CREB 유전자 발현과 항우울제에 대한 반응성

CREB Expression in Peripheral Lymphocyte and Antidepressant Response

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)