Abstract
We previously reported T cell deficits and pro-inflammatory gene activation in circulating monocytes of two cohorts of bipolar disorder (BD) patients, a cohort of postpartum psychosis patients and in bipolar offspring. Pro-inflammatory gene activation occurred in two clusters of mutually correlating genes, cluster 1 for inflammation-related cytokines/factors, cluster 2 for motility, chemotaxis, and metabolic factors. To verify these cellular immune abnormalities in yet another cohort [the bipolar stress study (BiSS) cohort] of relative old (52 years, median) BD patients and to relate immune abnormalities to hair cortisol levels, measured in this cohort and representing long-term systemic cortisol levels, and to the presence of the metabolic syndrome (MetS), which was prevalent in 29% of the BiSS patients. Monocyte immune gene activation (quantitative polymerase chain reaction) and T cell deficits (fluorescence-activated cell sorting analysis) were determined in 97 well-controlled, largely euthymic BiSS BD patients. Monocyte genes included the cluster 1 and 2 genes, the genes for the glucocorticoid receptor (GR) α and GRβ, and the gene for hepatocyte growth factor [HGF, a marker of monocyte-derived circulating angiogenic cells (CACs)]. CACs serve vessel repair. Abnormal numbers are found in patients with MetS and vascular damage. As compared to healthy controls: (1) the pro-inflammatory cluster 1 genes were downregulated, and the GRα and the HGF gene were upregulated in the monocytes of the BiSS patients and (2) T cell deficits were shown (reduced numbers of lymphocytes in particular of T cells). Within the reduced T cell population, a shift had taken place in the T-helper populations: T-helper 17 and T-helper 2 increased and T regulatory cells decreased. Correlations between hair cortisol, the MetS, monocyte gene activation, and T cell deficits were not found. T cell deficits most likely are a trait phenomenon of BD, since they have also been found in the other cohorts of BD patients and in bipolar offspring. Monocytes of this cohort showed an anti-inflammatory set point, suggesting that pro- and anti-inflammation are state characteristics of BD. The monocyte gene profile indicated an increased CAC activity; the question arises whether this is due to putative vessel damage in these relatively old patients with a high prevalence of the MetS.
Highlights
The last 10 years evidence has accumulated that dysfunctions of T cells, and monocytes/macrophages are important factors in the development of bipolar disorder (BD)
Monocyte gene expression of patients was compared to monocyte gene expression of 47 Healthy Controls (HCs) of whom blood was tested in the same assays
We are confident that this study shows that lymphopenia, and in particular a reduced percentage of T cells, is a characteristic of relatively old BD patients
Summary
The last 10 years evidence has accumulated that dysfunctions of T cells, and monocytes/macrophages are important factors in the development of bipolar disorder (BD). We have studied [1] a cohort of 56 BD patients from the Dutch site of the Stanley Foundation Bipolar Network (D-SFBN) cohort, mean age 42 years [2, 3], [2] a cohort of 90 BD patients, aged 43 years (mean) from the MOODINFLAME-Groningen-Leuven site [4], and [3] a cohort of 140 children of a bipolar parent in follow-up, from 16 through 29 years, the so-called Dutch bipolar offspring (DBO) study [5] In these studies, we detected that the monocytes of subjects were characterized by the abnormal expression of two coherent clusters of inflammation-related genes. Aim: To verify these cellular immune abnormalities in yet another cohort [the bipolar stress study (BiSS) cohort] of relative old (52 years, median) BD patients and to relate immune abnormalities to hair cortisol levels, measured in this cohort and representing long-term systemic cortisol levels, and to the presence of the metabolic syndrome (MetS), which was prevalent in 29% of the BiSS patients
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