T-lymphocyte CREB as a potential biomarker of response to antidepressant drugs

• Published in: The international journal of neuropsychopharmacology Vol. 16; no. 5; pp. 967 - 974
• Main Authors: Lim, Shinn-Won, Kim, Seonwoo, Carroll, Bernard J., Kim, Doh Kwan
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.06.2013; Oxford University Press
• Subjects: Aged; Aged, 80 and over; Antidepressants; Antidepressive Agents - pharmacology; Antidepressive Agents - therapeutic use; Biomarkers; CD3 Complex - metabolism; Cyclic AMP; Cyclic AMP Response Element-Binding Protein - metabolism; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - pathology; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; ROC Curve; Serotonin Uptake Inhibitors - pharmacology; T-Lymphocytes - drug effects; T-Lymphocytes - metabolism; Antidepressant; CREB; peripheral lymphocyte; depression; biomarker
• ISSN: 1461-1457; 1469-5111; 1469-5111
• DOI: 10.1017/S1461145712001125

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.