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

Rationale: 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. Objectives: By investigating circulating leukocyte subsets quantified by fluorescence-activated cell sorting (FACS) analysis before treatment, we aim to predict antidepressant response. Methods: 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. Results: Prior to treatment, MDD patients showed reduced percentages of CD4+CD25highFoxp3+ T regulatory (Treg) cells when compared with controls (1.5 ± 0.6 vs. 1.8 ± 0.6, p =.037). After treatment, robust rises in Treg cells were observed in patients (1.8 ± 0.7, p <.001), yet Treg 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. Conclusion: In melancholic MDD, FACS analysis of circulating leukocyte subpopulations might help to discriminate between patients with high or low responsiveness to antidepressant treatment.

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