Full-length ArticleA dynamic course of T cell defects in individuals at risk for mood disorders

•A subtle, partial T cell deficiency has been found in bipolar offspring over time.•T cell subsets followed a dynamic course from adolescence into adulthood.•During adolescence, a high inflammatory state was detected in bipolar offspring.•T cell aberrancies do not directly predict mood disorder development.

ObjectivesT 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.MethodsChildren 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.ResultsThroughout the period of observation reduced levels of CD3+ and CD3+ CD4+ T cells were observed. In bipolar offspring Th1, Th2, Th17 and natural T regulatory cells (Tregs) followed a dynamic course over time with reduced levels of Tregs in adolescence and a reduced relative number of Th1, Th17 cells in young adulthood. In post hoc analysis Tregs were inversely associated with the pro-inflammatory monocyte state determined previously (rs = −0.220, p = 0.001). Significant associations between T cell subset abnormalities and psychopathology such as mood disorders were not found.ConclusionsA 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.