CREB Expression in Peripheral Lymphocyte and Antidepressant Response.
- Author:
Ji Young SHIN
1
;
Shinn Won LIM
;
Sung Ho CHUNG
;
Hyeran KIM
;
Doh Kwan KIM
Author Information
1. Department of Neuropsychiatry, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. paulkim@smc.samsung.co.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
CREB;
Depression;
Antidepressant;
Lymphocyte
- MeSH:
Antidepressive Agents;
Blotting, Western;
Depression;
Electrophoretic Mobility Shift Assay;
Fluoxetine;
Humans;
Lymphocytes*;
Phosphorylation;
Response Elements;
Signal Transduction;
Transcription Factors
- From:Korean Journal of Psychopharmacology
2004;15(4):440-448
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
OBJECTIVE: The molecules related with the intracellular signal transduction system are one of the main targets for the mode of mechanisms of antidepressant treatment in 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) in 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 > or =50% of reduction or < 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 SPSS11.0. 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 peripheral lymphocyte may reflect and mediate the response to antidepressant treatment in depressed patients.
