The L-Arginine/NO Pathway in Children with Attention-Deficit/Hyperactivity Disorder (ADHD)

Background: Attention-deficit/hyperactivity disorder (ADHD) is the most common psychiatric disorder in children. Adults with ADHD are known to be at higher risk for cardiovascular diseases. ADMA, an endogenous inhibitor of NO synthesis, has been identified as a risk factor for cardiovascular disease in adults. The L-arginine/NO pathway in children with ADHD is poorly investigated as well as its metabolites’ potential role as biomarkers for cardiovascular risk.

Methods: Twenty-four children with ADHD without medication, 19 ADHD children undergoing treatment with methylphenidate and 33 healthy children were included. We measured plasma and urine levels of nitrite, nitrate and the amino acids ADMA and L-arginine using gas chromatography-mass spectrometry.

Results: Children with ADHD had higher ADMA levels in plasma than healthy children (0.51 ± 0.07 µM vs. 0.57 ± 0.11 µM; p = 0.011) and higher nitrite plasma levels (2.64 ± 0.87 µM vs. 1.69 ± 0.7 µM; p = 0.0002). In ADHD patients treated with methylphenidate, the nitrite levels were even higher than in patients without medication (3.2 ± 0.53 µM vs. 2.64 ± 0.87 µM; p = 0.003). There was no difference in the urine levels of all measured metabolites.

Conclusion: Our results suggest a higher NO synthesis in children with ADHD. If these findings point to a protective mechanism regarding the development of cardiovascular disease or if these are secondary effects of ADHD itself (physical activity, sympathetic nervous system activation) needs to be further investigated. ADMA might serve as a biomarker for the development of cardiovascular disease in ADHD patients.