Inflammatory Markers and Brain-Derived Neurotrophic Factor as Potential Bridges Linking Bipolar Disorder and Cardiovascular Risk Among Adolescents.

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.

Impulsivity is associated with blood pressure and waist circumference among adolescents with bipolar disorder.

OBJECTIVE: Cardiovascular risk factors (CVRFs) and impulsivity are common in bipolar disorder (BD), and CVRFs are also linked with impulsivity through a number of mechanisms, both behavioral and biological. This study examines the association between CVRFs and impulsivity in adolescents with BD. METHODS: Subjects were 34 adolescents with BD and 35 healthy control (HC) adolescents. CVRFs were based on International Diabetes Federation metabolic syndrome criteria (triglycerides, high-density lipoprotein cholesterol, waist circumference, blood pressure (BP) and glucose). Impulsivity was measured using the computerized Cambridge Gambling Task (CGT). Analyses controlled for age, IQ, lifetime attention deficit hyperactivity disorder, and current antipsychotic use. RESULTS: Adolescents with BD had higher diastolic BP (73.36 ± 9.57 mmHg vs. 67.91 ± 8.74 mmHg, U = 401.0, p = 0.03), higher triglycerides (1.13 ± 0.60 mmol/L vs. 0.78 ± 0.38 mmol/L, U = 373.5, p = 0.008), and were more likely to meet high-risk criteria for waist circumference (17.6% vs. 2.9%, p = 0.04) vs. HC. Within the BD group, CGT sub-scores were correlated with CVRFs. For example, overall proportion bet was positively correlated with systolic (r = 0.387, p = 0.026) and diastolic (ρ = 0.404, p = 0.020) BP. Quality of decision-making was negatively correlated with systolic BP (ρ = -0.401, p = 0.021) and waist circumference (ρ = -0.534, p = 0.003). Significant interactions were observed, such that BD diagnosis moderates the relationship between both waist circumference and BP with CGT sub-scores. CONCLUSION: BP and waist circumference are associated with impulsivity in BD adolescents, but not in HC adolescents. Future studies are warranted to determine temporality and to evaluate whether optimizing CVRFs improves impulsivity among BD adolescents.