Circulating cytotoxic T cells and natural killer cells as potential predictors for antidepressant response in melancholic depression. Restoration of T regulatory cell populations after antidepressant therapy

There is a substantial unmet need for biomarkers to predict treatment response in major depressive disorder (MDD). Evidence has converged on activation of the inflammatory response system as a fundamental mechanism underlying MDD. By investigating circulating leukocyte subsets quantified by fluorescence-activated cell sorting (FACS) analysis before treatment, we aim to predict antidepressant response. Forty medication-free inpatients with melancholic, non-psychotic depression before treatment with either venlafaxine or imipramine and 40 age- and gender-matched healthy controls were included. Leukocyte subsets were quantified by FACS analysis using frozen peripheral blood mononuclear cells (PBMC) collected prior to and after 7 weeks of treatment with either venlafaxine (375 mg/day) or imipramine (blood level 200-300 ng/ml). Response was defined as at least 50 % reduction of the baseline Hamilton Rating Scale for Depression (HAM-D) score. Prior to treatment, MDD patients showed reduced percentages of CD4(+)CD25(high)Foxp3(+) T regulatory (T-reg) cells when compared with controls (1.5 +/- 0.6 vs. 1.8 +/- 0.6, p = .037). After treatment, robust rises in T-reg cells were observed in patients (1.8 +/- 0.7, p < .001), yet T-reg cells were not predictors of the clinical outcome of treatment. Antidepressant non-responders showed increased CD8(+) cytotoxic T cell percentages (24.0 +/- 8.6 vs. 15.9 +/- 5.9, p = .004) and decreased natural killer (NK) cell percentages (14.0 +/- 6.9 vs. 21.4 +/- 11.9, p = .020) compared with responders before treatment. Both lymphocyte levels were not significantly modulated by treatment. In melancholic MDD, FACS analysis of circulating leukocyte subpopulations might help to discriminate between patients with high or low responsiveness to antidepressant treatment.