Flow-cytometric analysis of immune cell populations in patients with depression: relationship with depression severity and electroconvulsive therapy therapeutic outcomes

Abstract

Introduction: Immunological changes are implicated in the pathophysiology of depression. We aimed to assess phenotype and frequency of immune cell subtypes, including an assessment of regulatory T cells and production of cytokines by T cell subsets following stimulation.

Methods: Using a flow cytometric analysis, peripheral blood samples obtained from medicated patients with depression (n = 20) were analysed and compared to age-and sex-matched healthy controls (n = 21), and in patients with depression after electroconvulsive therapy (ECT) in a real-world clinical setting. Depression severity was assessed using the Hamilton Depression Rating Scale (HAM-D24).

Results: A reduction in the frequencies of CD19+ B cells and IL-17+ CD8 T cells was evident in depressed patients compared to healthy controls. For a subgroup of depressed patients assessed pre- versus post-ECT, there was no change in phenotype, frequency or function of immune cell subtypes within 72 hours of completing treatment. Further exploratory analyses found that baseline CD16-CD14+ classical monocyte frequency correlated with change in HAM-D24 score post-ECT, indicating that a higher frequency of classical monocytes at baseline is associated with greater symptom improvement after treatment. A reduced number of CCR7-CD45RO+ effector memory T cells was also found to be associated with an improvement in symptoms post-ECT.

Discussion: Overall, these results demonstrate that flow cytometry is useful for immune profiling to identify altered adaptive immune features in depression and potential biomarkers of ECT response. In particular, changes in classical monocytes and effector memory T cells were associated with treatment response in patients with unipolar depression.

Keywords: cytokine; depression; electroconvulsive therapy; flow cytometry; immune.

FIGURE 1

Immune cell populations and soluble immune markers associated with MDD.

FIGURE 2

(a) % CD19⁺ B-cells (of single cells): The frequency of CD19⁺ B-cells was significantly lower in the depressed patient group when compared to healthy controls. Each dot represents an individual subject. (b) % of IL-17⁺ (of CD8 T-cells): The frequency of IL-17⁺ CD8 T-cells was also significantly reduced in the depressed patient group relative to healthy controls. Each dot represents an individual subject. Data are presented as means ± SD. *p < 0.05.

FIGURE 3

Correlations between immune cell subsets and depressive symptom severity or change. (a) % CD16-CD14+ classical monocytes at baseline vs. Change in HAM-D24: Scatter plot showing the association between % CD16-CD14+ classical monocyte cell frequencies at baseline and the change in HAM-D24 scores over the study period. Each dot represents an individual subject; the red line indicates the line of correlation. (b) Change in Tem/CCR7^–CD45RO⁺ cells vs. Change in HAM-D24: Scatter plot depicting the relationship between the change in Tem/CCR7^–CD45RO⁺ cell frequencies and the change in HAM-D24 scores. Each dot represents an individual subject; the red line indicates the line of correlation. Abbreviations: HAM-D24, Hamilton Depression Rating Scale-24 item; Tem, effector memory T cells.