title: A dynamic course of T cell defects in individuals at risk for mood disorders.
abstract: OBJECTIVE
  T 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.
  
  
  METHODS
  Children 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.
  
  
  RESULTS
  Throughout 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 Tregsin adolescence and a reduced relative number of Th1, Th17 cells in young adulthood. In post hoc analysis Tregswere 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.
  
  
  CONCLUSIONS
  A 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.
authors.affiliation: Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: g.j.l.j.snijders@umcutrecht.nl.
authors.forename: G
authors.initials: G
authors.lastname: Snijders
authors.affiliation: The University Psychiatric Centre KU Leuven, Leuven, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Schiweck
authors.affiliation: Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Mesman
authors.affiliation: Department of Psychiatry, University of Munster, Münster, Germany; Radiology Morphological Solutions, Rotterdam, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Grosse
authors.affiliation: Erasmus Medical Center Rotterdam/Department of Immunology, Rotterdam, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: De Wit
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands.
authors.forename: W A
authors.initials: WA
authors.lastname: Nolen
authors.affiliation: Erasmus Medical Center Rotterdam/Department of Immunology, Rotterdam, The Netherlands.
authors.forename: H A
authors.initials: HA
authors.lastname: Drexhage
authors.affiliation: Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: M H J
authors.initials: MHJ
authors.lastname: Hillegers
mesh_terms: D000293:Adolescent; D001714:Bipolar Disorder / Q000235:genetics; D002648:Child; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000276:immunology; D007694:Killer Cells, Natural / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000378:metabolism; D019964:Mood Disorders / Q000150:complications / Q000235:genetics* / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D055815:Young Adult
keywords: Bipolar disorder; Gene expression; High risk; Inflammation; Mood disorder; Natural T regulatory cells; T cells