T-lymphocyte CREB as a potential biomarker of response to antidepressant drugsopen access
- Authors
- Lim, SW[Lim, Shinn-Won]; Kim, S[Kim, Seonwoo]; Carroll, BJ[Carroll, Bernard J.]; Kim, DK[Kim, Doh Kwan]
- Issue Date
- Jun-2013
- Publisher
- CAMBRIDGE UNIV PRESS
- Keywords
- Antidepressant; biomarker; CREB; depression; perip
- Citation
- INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, v.16, no.5, pp.967 - 974
- Indexed
- SCIE
SCOPUS
- Journal Title
- INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
- Volume
- 16
- Number
- 5
- Start Page
- 967
- End Page
- 974
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/60402
- DOI
- 10.1017/S1461145712001125
- ISSN
- 1461-1457
- Abstract
- Response to drug treatment of major depression is variable and biomarkers of response are needed. Cyclic AMP response element binding protein (CREB) is considered a key mediator of antidepressant drug effect. We studied CREB in T-lymphocytes as a potential predictor of response to a selective serotonin reuptake inhibitor (SSRI) in 69 Korean depressed patients. We determined total CREB (tCREB), phosphorylated CREB (pCREB) and CRE-DNA binding using immunoblot and electrophoretic mobility shift assays, at baseline and after 6 wk treatment. Thirty-four healthy controls were also studied. The rate of response was 36 of 69 cases (52%). Baseline levels of tCREB and pCREB were lower in the total depressed group compared to controls (p = 0.044 and p < 0.001, respectively). Baseline tCREB values in responders were significantly reduced in comparison to non-responders and to controls. After 6 wk treatment, median values of change of all CREB measures were greater in responders (36) than in non-responders (33; p < 0.001 for tCREB, p = 0.003 for pCREB, and p = 0.072 for CRE-DNA binding). Similar but less robust changes in CREB variables distinguished remitters from non-remitters. The optimum value of baseline tCREB predicted response with a positive predicted value of 0.778 [21/27; 95% confidence intervals (CI) 0.621-0.935], negative predictive value of 0.643 (27/42; 95% CI 0.498-0.788) and accuracy of 0.695 (48/69; 95% CI 0.586-0.804). Patients with low baseline tCREB had a significantly greater rate of response (78%) than patients with high baseline tCREB (36%), p < 0.001. Moreover, the greatest changes in tCREB with treatment were observed in subjects who did respond. This preliminary study suggests that T-lymphocytic CREB biomarkers are reduced in depressed patients and may assist in the prediction of response to SSRI drugs in depression.
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