Cortisol and inflammatory biomarker levels in youths with attention deficit hyperactivity disorder (ADHD): evidence from a systematic review with meta-analysis.

Several studies reported abnormal cortisol and inflammatory biomarker levels in youths with attention deficit hyperactivity disorder (ADHD), but the results have not been conclusive. We conducted a systematic review followed by a meta-analysis of case-control studies assessing blood or saliva cortisol levels and blood levels of inflammatory biomarkers in youth with ADHD. The effect sizes (ES) were synthesized by using a random-effects model. In the 19 studies on cortisol levels (totaling n = 916 youth with ADHD and n = 947 typically developing (TD), healthy youth), youth with ADHD have lower basal cortisol levels at any time-points during the day (effect size: .68; p = 0.004) and lower cumulative levels of cortisol (ES: .39, p = .008) throughout the day than TD youth. Moreover, morning cortisol levels were lower in ADHD youth when compared with TD youth (14 studies, n = 1679, ES: .84, p = 0.003), while there is no difference for the afternoon cortisol levels (p = 0.48). The meta-analysis on inflammation biomarker was conducted on 4 studies (totaling n = 404 youth) showed that Tumour Necrosis Factor-alpha (TNF-α) was lower in ADHD when compared with TD (3 studies, n = 257 youth, p = 0.004), while no differences for Interleukin-1β(IL-1β) (p = 0.21), IL-6 (p = 0.09) and IL-10 (p = 0.77). The lower cortisol in the context of low TNF-α levels may indicate a specific pattern of biomarkers in ADHD, and further investigation is warranted.