33.1 PREDICTION VALUE OF NEUROIMMUNE ABNORMALITIES IN BIPOLAR OFFSPRING

Objectives: Several potential immune markers have been introduced in the field of mood disorders. However, the clinical implications of these markers are not clearly defined. The aim of this study is to investigate the predictive value of early phase peripheral neuroimmune biomarkers in a longitudinally study cohort of bipolar offspring. Confirmed immune markers of psychopathology in this high risk population may support the development of personalized prediction models in a routine clinical practice. Methods: Participants of the Dutch Bipolar Offspring Study (n = 140) were assessed during adolescence, young adulthood, and adulthood. T-cell percentages were measured by fluorescence-activated cell sorting analysis. A quantitative polymerase chain reaction case-control monocyte gene expression analysis was performed. Serum levels of thyroid peroxidase antibody (TPO-abs), S100 calcium-binding protein B (S100B), brain-derived neurotrophic factor (BDNF), insulin-like growth factor-binding protein 2 (IGFBP-2), soluble CD25, interleukin (IL)-7, stem cell factor (SCF), epidermal growth factor (EGF), pentraxin-related gene (PTX-3), and IL-1b were measured using a Luminex Cytometric Bead Array analyzer, in-house enzyme-linked immunosorbent assay, and electrochemiluminescence immunoassay. Results: In bipolar offspring, of the 13 percent who developed BD and 54 percent who developed a lifetime mood disorder at a 12-year follow-up, an activated immune and reduced neurotropic state was observed during adolescence. 1) The activation state of circulating monocytes, serum levels of proinflammatory cytokine PTX-3, and the seroprevalence of TPO-abs was significantly higher; 2) the percentages of anti-inflammatory natural regulatory T cells and serum BDNF, EGF, and S100B levels were markedly lower; and 3) neuroimmune growth/differentiation factors SCF, IL-7, and IGFBP-2 were raised in serum. During young adulthood, an anti-inflammatory was present in bipolar offspring. 1) The expression of proinflammatory genes was reduced; and 2) percentages of Th1 and Th17 cells were decreased significantly. At adulthood, these neuroimmune aberrancies virtually disappeared. Abnormalities were independent of the (future) psychopathology state at all stages. Conclusions: This study shows preexisting and fluctuating aberrancies in the immune/neurotrophic state in bipolar offspring. These neuroimmune aberrancies, however, do not predict the disorder directly. More complex risk profile construct