Cortisol, inflammatory biomarkers and neurotrophins in children and adolescents with attention deficit hyperactivity disorder (ADHD) in Taiwan

Background: Hypothalamus-Pituitary-Adrenal (HPA) axis dysregulation, inflammation and imbalance of neurotrophins have been suggested in attention deficit hyperactivity disorder (ADHD), but the results have not been conclusive. The aim of this study is to investigate the levels of salivary cortisol across 4-time points during the day, and of morning plasma inflammatory biomarkers and neurotrophins, in youth with ADHD and in typically developing youth (TD), with stratification by age, ADHD subtypes and oppositional defiant disorder (ODD) comorbidity in Taiwan. Methods: We conducted a case-control study measuring saliva cortisol levels at 4 different time points during the day (at awakening, noon, 1800 h and bedtime) and morning plasma levels of inflammatory and neurotrophins biomarkers in youth with ADHD (n = 98, age 6-18 years old with mean age 9.32 +/- 3.05 years) and TD (n = 21, age 6-18 years old with mean age 9.19 +/- 2.96 years) in Taiwan. Results: Our study showed that youth with ADHD had lower levels of bedtime salivary cortisol (effects size (ES) = -0.04, p =.023), with children with the combined form of the disorder (with inattention, hyperactivity and impulsivity all present) having the lowest awakening salivary cortisol levels. ADHD youth also had higher levels of plasma high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6 (ES = 0.85-1.20, p <.0001), and lower plasma tumor necrosis factor-alpha (ES = -0.69, p =.009) and brain-derived neurotrophic factors (BDNF) (ES = -1.13, p <.0001). Both ADHD groups regardless of ODD comorbidity had higher levels of IL-6 (p <.0001) and lower levels BDNF (p <.0001). Conclusion: The lower bedtime salivary cortisol levels and higher levels of inflammatory biomarkers in youth with ADHD further support the role of abnormal HPA axis and inflammation in ADHD. Moreover, the lower levels of BDNF in ADHD also indicate that BDNF may be a potential biomarker in this disorder that is part of a broader biological dysfunction.