title: Inflammatory Markers and Brain-Derived Neurotrophic Factor as Potential Bridges Linking Bipolar Disorder and Cardiovascular Risk Among Adolescents.
abstract: OBJECTIVE
  Bipolar disorder (BD) is associated with increased rates of cardiovascular disease (CVD). Brain-derived neurotrophic factor (BDNF) and inflammatory markers are leading biomarkers in BD. We examined whether these biomarkers underlie the link between BD and CVD proxies among adolescents with bipolar spectrum disorders.
  
  
  METHODS
  Subjects were 60 adolescents, 13-19 years old (40 with BD and 20 healthy controls [HCs]). Semistructured interviews determined diagnoses based on DSM-IV. Serum was assayed for BDNF, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Carotid intima media thickness (cIMT) and flow-mediated dilation were assessed using ultrasound. Procedures were conducted at a subspecialty clinic (January 2011-May 2014).
  
  
  RESULTS
  Adolescents with BD had significantly greater waist circumference (BD: 81.72 cm [11.67 cm], HC: 75.64 cm [8.63 cm]; U = 547.5, P = .021), body mass index (BMI) (BD: 25.50 kg/m²undefined[5.29 kg/m²], HC: 21.76 kg/m² [3.43 kg/m²]; U = 608.5, P < .0001), pulse pressure (BD: 42.31 mm Hg [10.57 mm Hg], HC: 33.84 mm Hg [6.69 mm Hg]; U = 561.5, P < .001), and IL-6 (BD: 8.93 pg/mL [7.71 pg/mL], HC: 4.96 pg/mL [6.38 pg/mL]; U = 516.0, P < .0001) than HC adolescents. Subjects with BD-I (n = 14) and BD-II (n = 16) had greater IL-6 versus HCs (F₃,₅₁ = 5.29, P = .003). Controlling for BMI and age did not alter these findings. IL-6 was higher in symptomatic (n = 19) and asymptomatic BD (n = 21) versus that found in HCs (F₂,₅₂ = 7.96, P = .001). In symptomatic BD, lower BDNF was associated with greater mean cIMT (ρ = -0.507, P = .037).
  
  
  CONCLUSIONS
  This study found evidence of increased inflammation among adolescents with BD. While present findings suggest a potential interplay between symptomatic status, biomarkers, and atherosclerosis proxies, there were no significant differences in cIMT or flow-mediated dilation in adolescents with BD compared to HCs. This may indicate that there is potential opportunity for CVD prevention strategies in adolescents with BD.
authors.affiliation: Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.|Department of Pharmacology and Toxicology, University of Toronto, Ontario, Canada.
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Hatch
authors.affiliation: Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Scola
authors.affiliation: Department of Medical Imaging, University of Toronto, Ontario, Canada.
authors.forename: Omodele
authors.initials: O
authors.lastname: Olowoyeye
authors.affiliation: Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
authors.forename: Jordan E
authors.initials: JE
authors.lastname: Collins
authors.affiliation: Department of Psychiatry, University of Toronto, Ontario, Canada.|Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Andreazza
authors.affiliation: Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.|Department of Medical Imaging, University of Toronto, Ontario, Canada.|Division of Cardiology, Department of Medicine, Sunnybrook Health Sciences Centre, Schulich Heart Program, Toronto, Ontario, Canada.
authors.forename: Alan
authors.initials: A
authors.lastname: Moody
authors.affiliation: Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Levitt
authors.affiliation: Division of Cardiology, Department of Medicine, Sunnybrook Health Sciences Centre, Schulich Heart Program, Toronto, Ontario, Canada.
authors.forename: Bradley H
authors.initials: BH
authors.lastname: Strauss
authors.affiliation: Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.|Department of Pharmacology and Toxicology, University of Toronto, Ontario, Canada.
authors.forename: Krista L
authors.initials: KL
authors.lastname: Lanctot
authors.affiliation: Department of Psychiatry, Sunnybrook Health Sciences Centre, FG-53, 2075 Bayview Ave, Toronto ON, Canada, M4N3M5. benjamin.goldstein@sunnybrook.ca.|Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.|Department of Pharmacology and Toxicology, University of Toronto, Ontario, Canada.
authors.forename: Benjamin I
authors.initials: BI
authors.lastname: Goldstein
mesh_terms: D000293:Adolescent; D001714:Bipolar Disorder / Q000097:blood* / Q000453:epidemiology; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D007406:Interview, Psychological; D008297:Male; D012307:Risk Factors; D013223:Statistics as Topic; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D017539:Tunica Intima / Q000503:physiopathology; D014664:Vasodilation / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C579455:BDNF protein, human