ABSTRACT
Inflammatory cytokines are involved in attention deficit hyperactivity disorder (ADHD), a highly prevalent neurodevelopmental disorder. To quantify the baseline levels of pro- and anti-inflammatory cytokines and their changes after methylphenidate (MPH), a total of 31 prepubertal children with ADHD were recruited and subclassified into only two ADHD presentations-ADHD attention deficit (n = 13) or ADHD combined (n = 18). The children were also screened for oppositional defiant conduct disorder (ODCD) and anxiety disorder. Blood samples were drawn at 09:00 and after 4.63 ± 1.87 months of treatment. Four pro-inflammatory cytokines (interleukin-1beta (IL-1ß), IL-5, IL-6, tumor necrosis factor-alpha (TNF-α)) and three anti-inflammatory cytokines (IL-4, IL-10, IL-13) were measured using a Luminex® assay. For statistics, a factorial analysis was performed in Stata 15.1. Overall, there were no statistically significant differences in the interleukin (IL) values induced by treatment. When grouped by presentation, the differences were present almost exclusively in ADHD-AD, usually with a profile opposite to that observed in ADHD-C, and with interactions between comorbid factors, with IL-1ß (p = 0.01) and IL-13 (p = 0.006) being the ones reaching the greatest statistical significance. These differences are probably related to the ODCD factor, and they disappear after treatment. In conclusion, the changes observed in cytokine levels in prepubertal children only in the ADHD-AD presentation are probably related to comorbidities (specifically ODCD) and are mitigated after treatment.
ABSTRACT
Although ADHD is one of the most prevalent diseases during childhood, we still do not know its precise origin; oxidative/nitrosative stress and the hypothalamic-pituitary-adrenal axis are suggested contributors. Methylphenidate, among others, is the main drug used in ADHD patients, but its effects on relevant markers and structures remain unclear. This study, involving 59 patients diagnosed with ADHD according to DSM-5 criteria, aimed to assess changes in cortisol levels (using cortisol awakening response, CAR) and oxidative/nitrosative status with the treatment. Blood samples before and 3 months after treatment with methylphenidate were used to measure oxidative and inflammatory markers, as well as the endogenous antioxidant activity, while saliva samples tracked cortisol awakening response (CAR). The results showed a treatment-related improvement in the redox profile, with the reduction in advanced oxidation protein products (AOPP), lipid peroxidation (LPO), and nitrite plus nitrate (NOx) levels, and the increase in the enzymatic activities of glutathione reductase (GRd) and catalase (CAT). Moreover, the area under the curve (AUC) of CAR increased significantly, indicating increased reactivity of the HPA axis. These results support, for the first time, the involvement of the endogenous antioxidant system in the pathophysiology of ADHD.