A dynamic course of T cell defects in individuals at risk for mood disorders.

Abstract Objectives T cell abnormalities have been repeatedly reported in adult patients with mood disorders, suggesting a role of these cells in the pathogenesis of these disorders. In the present study, we explored the dynamics of circulating T cell subsets over time in a population at high familial risk for developing a mood disorder. Methods Children of a parent with bipolar disorder (bipolar offspring, N  = 140) were assessed at three time-points: adolescence, young adulthood and adulthood. We carried out a detailed fluorescence-activated cell sorting (FACS) analysis to determine various T cell subsets from frozen stored peripheral blood mononuclear cells of bipolar offspring and age- and gender-matched healthy controls at each time-point. Results Throughout the period of observation reduced levels of CD3+ and CD3+ CD4+ T cells were observed. In bipolar offspring T h 1, T h 2, T h 17 and natural T regulatory cells (T regs ) followed a dynamic course over time with reduced levels of T regs in adolescence and a reduced relative number of T h 1, T h 17 cells in young adulthood. In post hoc analysis T regs were inversely associated with the pro-inflammatory monocyte state determined previously ( r s  = −0.220 , p =  0.001). Significant associations between T cell subset abnormalities and psychopathology such as mood disorders were not found. Conclusions A subtle partial T cell defect was present in bipolar offspring from adolescence through adulthood. Within this defect the dynamic change of inflammatory and regulatory T cell subsets suggests a high inflammatory state during adolescence, a reduced inflammatory state during young adulthood and a virtually normalized state at adulthood.