Effects of agmatine, glutamate, arginine, and nitric oxide on executive functions in children with attention deficit hyperactivity disorder

In this study, we aimed to investigate the effects of agmatine, nitric oxide (NO), arginine, and glutamate, which are the metabolites in the polyamine pathway, on the performance of executive functions (EF) in attention deficit hyperactivity disorder (ADHD). The ADHD group included 35 treatment-naive children (6-14 years old) who were ewly diagnosed with ADHD. The control group consisted of 35 healthy children with the same age and sex, having no previous psychiatric disorders. In the study groups, Stroop test (ST) and trail making test (TMT) were used to monitor EF, and blood samples were collected to measure agmatine with ultra-high-performance liquid chromatography and NO, glutamate, and arginine with enzyme-linked immunosorbent assay (ELISA). The EFs were significantly impaired in the ADHD group. The agmatine and arginine levels of the ADHD group were significantly higher than their peers. The NO and glutamate levels were also higher in the ADHD group compared to the control group, but these differences did not reach statistical significance. Children with ADHD had more difficulties during EF tasks compared to healthy children. The elevated NO and glutamate levels may be related with the impairment during EF tasks. Therefore, agmatine and arginine may increase to improve EF tasks through its inhibitory effect on the synthesis of NO and glutamate. Further studies are needed about polyamine pathway molecules to shed light on the pathophysiology of ADHD.