Genetic and environmental influences on circulating NK and T cells and their relation to bipolar disorder

Background: In previous studies we found mild defciencies of circulating T cells in patients with bipolar disorder (BD) and children at risk for BD, correlating to a higher infammatory state. The genetic and environmental infuences on these T cell defciencies in association with BD development are unknown. Objectives: The aim is to quantify genetic and environmental factors that contribute to the association between the liability to develop BD and T cell defciencies. Methods: Participants of a Dutch bipolar twin study (11 monozygotic BD twin pairs, 15 dizygotic BD twin pairs, 15 monozygotic and 12 dizygotic healthy twin pairs) were included. A detailed FACS analysis of frozen stored leukocytes was carried out to determine the percentages of T cells and various other leukocyte and lymphocyte subsets. A bivariate liability threshold twin model was used to determine genetic and environmental (common and unique) infuences on the correlation between BD and the various subsets. Results: Lower percentages of T cells and higher percentages of NK cells were associated with the familial liability to develop BD. Neither genetic nor shared or unique environmental factors could explain the associations. Lithium usage explained part of the association for T cells, smoking in part that for NK cells. Conclusions: Our results confrm that BD is the result of a complex interaction between various genetic and environmental risk factors, in which T and NK cells act as important intermediate immune players.

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