title: Monocyte activation, brain-derived neurotrophic factor (BDNF), and S100B in bipolar offspring: a follow-up study from adolescence into adulthood.
abstract: OBJECTIVE
  There is increasing evidence that both immune and neurochemical alterations are involved in the pathogenesis of bipolar disorder; however, their precise role remains unclear. In this study, we aimed to evaluate neuro-immune changes in a prospective study on children of patients with bipolar disorder.
  
  
  METHODS
  Bipolar offspring, from the prospective Dutch bipolar offspring study (n = 140), were evaluated cross-sectionally within a longitudinal context at adolescence, young adulthood, and adulthood. We examined the expression of 44 inflammation-related genes in monocytes, the cytokines pentraxin 3 (PTX3), chemokine ligand 2 (CCL2), and interleukin-1β (IL-1β), and brain-derived neurotrophic factor (BDNF) and S100 calcium binding protein B (S100B) in the serum of bipolar offspring and healthy controls.
  
  
  RESULTS
  During adolescence, bipolar offspring showed increased inflammatory gene expression in monocytes, high serum PTX3 levels, but normal CCL2 levels. BDNF levels were decreased, while S100B levels were normal. During young adulthood, monocyte activation remained, although to a lesser degree. Serum PTX3 levels remained high, and signs of monocyte migration became apparent through increased CCL2 levels. BDNF and S100B levels were not measured. At adulthood, circulating monocytes had lost their activation state, but CCL2 levels remained increased. Both BDNF and S100B were now increased. Abnormalities were independent of psychopathology state at all stages.
  
  
  CONCLUSIONS
  This study suggests an aberrant neuro-immune state in bipolar offspring, which followed a dynamic course from adolescence into adulthood and was present irrespective of lifetime or future mood disorders. We therefore assumed that the aberrant neuro-immune state reflects a general state of vulnerability for mood disorders rather than being of direct predictive value.
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: Mesman
authors.forename: Manon Hj
authors.initials: MH
authors.lastname: Hillegers
authors.forename: Oliver
authors.initials: O
authors.lastname: Ambree
authors.forename: Volker
authors.initials: V
authors.lastname: Arolt
authors.forename: Willem A
authors.initials: WA
authors.lastname: Nolen
authors.forename: Hemmo A
authors.initials: HA
authors.lastname: Drexhage
mesh_terms: D000293:Adolescent; D000328:Adult; D001714:Bipolar Disorder / Q000175:diagnosis / Q000276:immunology / Q000523:psychology; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis; D016241:Child of Impaired Parents / Q000523:psychology*; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000276:immunology; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood*; D000683:Serum Amyloid P-Component / Q000032:analysis; D013223:Statistics as Topic; D000099153:Pentraxins
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002097:C-Reactive Protein; D053583:Interleukin-1beta; D064568:S100 Calcium Binding Protein beta Subunit; D000683:Serum Amyloid P-Component; D000099153:Pentraxins; C579160:S100B protein, human; C579455:BDNF protein, human
keywords: biomarker; bipolar disorder; brain-derived neurotrophic factor (BDNF); cytokines; high risk; inflammation