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.