title: T Cell Deficits and Overexpression of Hepatocyte Growth Factor in Anti-inflammatory Circulating Monocytes of Middle-Aged Patients with Bipolar Disorder Characterized by a High Prevalence of the Metabolic Syndrome.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Immunology, Erasmus Medical Center , Rotterdam , Netherlands.
authors.forename: Rogier J
authors.initials: RJ
authors.lastname: Vogels
authors.affiliation: Department of Mood Disorders, PsyQ , Rotterdam , Netherlands.
authors.forename: Manja A
authors.initials: MA
authors.lastname: Koenders
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, Netherlands; Obesity Center CGG, Rotterdam, Netherlands.
authors.forename: Elisabeth F C
authors.initials: EF
authors.lastname: van Rossum
authors.affiliation: Department of Mood Disorders, PsyQ , Rotterdam , Netherlands.
authors.forename: Annet T
authors.initials: AT
authors.lastname: Spijker
authors.affiliation: Department of Immunology, Erasmus Medical Center , Rotterdam , Netherlands.
authors.forename: Hemmo A
authors.initials: HA
authors.lastname: Drexhage
keywords: T cell deficits; angiogenic cells; bipolar disorder; gene expression; hypothalamic–pituitary–adrenal axis