title: T-lymphocyte CREB as a potential biomarker of response to antidepressant drugs.
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.
authors.affiliation: Center for Clinical Research, Samsung Biomedical Research Institute, Seoul, Korea.
authors.forename: Shinn-Won
authors.initials: SW
authors.lastname: Lim
authors.forename: Seonwoo
authors.initials: S
authors.lastname: Kim
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Carroll
authors.forename: Doh Kwan
authors.initials: DK
authors.lastname: Kim
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017252:CD3 Complex / Q000378:metabolism; D000242:Cyclic AMP; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012372:ROC Curve; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; D017252:CD3 Complex; D000242:Cyclic AMP; D017362:Cyclic AMP Response Element-Binding Protein; D017367:Selective Serotonin Reuptake Inhibitors