title: Inflammatory markers among adolescents and young adults with bipolar spectrum disorders.
abstract: OBJECTIVE
  Despite burgeoning literature in middle-aged adults, little is known regarding proinflammatory markers (PIMs) among adolescents and young adults with bipolar disorder. Similarly, few prior studies have considered potential confounds when examining the association between PIMs and bipolar disorder characteristics. We therefore retrospectively examined these topics in the Course and Outcome of Bipolar Youth (COBY) study.
  
  
  METHODS
  Subjects were 123 adolescents and young adults (mean [SD] = 20.4 ± 3.8 years; range, 13.4-28.3 years) in COBY, enrolled between October 2000 and July 2006. DSM-IV diagnoses were determined using the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS). Clinical characteristics during the preceding 6 months, including mood, comorbidity, and treatment, were evaluated using the Longitudinal Interval Follow-Up Evaluation (LIFE). Serum levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and high-sensitivity C-reactive protein (hsCRP) were assayed. Primary analyses examined the association of PIMs with bipolar disorder characteristics during the preceding 6 months.
  
  
  RESULTS
  Several lifetime clinical characteristics were significantly associated with PIMs in multivariable analyses, including longer illness duration (P = .005 for IL-6; P = .0004 for hsCRP), suicide attempts (P = .01 for TNF-α), family history of suicide attempts or completion (P = .01 for hsCRP), self-injurious behavior (P =.005 for TNF-α), substance use disorder (SUD) (P < .0001 for hsCRP), and family history of SUD (P = .02 for TNF-α; P = .01 for IL-6). The following bipolar disorder characteristics during the preceding 6 months remained significantly associated with PIMs in multivariable analyses that controlled for differences in comorbidity and treatment: for TNF-α, percentage of weeks with psychosis (χ(2) = 5.7, P =.02); for IL-6, percentage of weeks with subthreshold mood symptoms (χ(2)= 8.3, P = .004) and any suicide attempt (χ(2) = 6.1, P = .01); for hsCRP, maximum severity of depressive symptoms (χ(2) = 8.3, P =.004).
  
  
  CONCLUSIONS
  Proinflammatory markers may be relevant to bipolar disorder characteristics as well as other clinical characteristics among adolescents and young adults with bipolar disorder. Traction toward validating PIMs as clinically relevant biomarkers in bipolar disorder will require repeated measures of PIMs and incorporation of relevant covariates.
authors.affiliation: Department of Psychiatry, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, FG53, Toronto, Ontario, M4N-3M5 Benjamin.Goldstein@sunnybrook.ca.
authors.forename: Benjamin I
authors.initials: BI
authors.lastname: Goldstein
authors.forename: Francis
authors.initials: F
authors.lastname: Lotrich
authors.forename: David A
authors.initials: DA
authors.lastname: Axelson
authors.forename: Mary Kay
authors.initials: MK
authors.lastname: Gill
authors.forename: Heather
authors.initials: H
authors.lastname: Hower
authors.forename: Tina R
authors.initials: TR
authors.lastname: Goldstein
authors.forename: Jieyu
authors.initials: J
authors.lastname: Fan
authors.forename: Shirley
authors.initials: S
authors.lastname: Yen
authors.forename: Rasim
authors.initials: R
authors.lastname: Diler
authors.forename: Daniel
authors.initials: D
authors.lastname: Dickstein
authors.forename: Michael A
authors.initials: MA
authors.lastname: Strober
authors.forename: Satish
authors.initials: S
authors.lastname: Iyengar
authors.forename: Neal D
authors.initials: ND
authors.lastname: Ryan
authors.forename: Martin B
authors.initials: MB
authors.lastname: Keller
authors.forename: Boris
authors.initials: B
authors.lastname: Birmaher
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D012189:Retrospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein