Objectives: To investigate the effect of long-term lithium treatment on very small embryonic-like stem cells (VSELs), haematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) circulating in peripheral blood (PB), in bipolar disorder (BD).
Methods: The study included 15 BD patients (aged 55 ± 6 years) treated with lithium for 8-40 years (mean 16 years), 15 BD patients (aged 53 ± 7 years) with duration of illness >10 years, who had never received lithium, and 15 healthy controls (aged 50 ± 5 years). The VSELs, HSCs, MSCs and EPCs were measured by flow cytometric analysis.
Results: In BD subjects not taking lithium the number of CD34+ VSELs was significantly higher, and MSCs and EPCs numerically higher, than in control subjects and the number of CD34+ VSELs correlated with the duration of illness. In lithium-treated patients these values were similar to controls and the number of CD34+ VSELs correlated negatively with the duration of lithium treatment and serum lithium concentration.
Conclusions: Long-term treatment with lithium may suppress the activation of regenerative processes by reducing the number of VSELs circulating in PB. These cells, in BD patients not treated with lithium, may provide a new potential biological marker of the illness and its clinical progress.
Keywords: Bipolar disorder; lithium; staging; stem cells; very small embryonic-like stem cells.