Attention-deficit/hyperactivity disorder, Tourette's syndrome, and restless legs syndrome: the iron hypothesis

Preliminary but increasing evidence suggests that attention-deficit/hyperactivity disorder (ADHD), Tourette's syndrome (TS), and restless legs syndrome (RLS) may be comorbid. In the present article, we hypothesize that ADHD, TS, and RLS may be part of a spectrum, and that iron deficiency contributes to the pathophysiology underlying this spectrum. Iron deficiency might lead to ADHD, RLS and TS symptoms via its impact on the metabolism of dopamine and other catecholamines, which have been involved into the pathophysiology of ADHD, TS, and RLS. We speculate that the catecholaminergic systems are differently impacted in each of the three disorders, contributing to a different specific phenotypic expression of iron deficiency. MRI studies assessing brain iron levels in ADHD, TS, and childhood RLS, as well as genetic studies on the specific molecular pathways involved in iron deficiency, are greatly needed to confirm the iron hypothesis underlying ADHD, TS, and RLS. This body of research may set the basis for controlled trials assessing the effectiveness and tolerability, as well as the most appropriate dose, duration and type (oral vs. intravenous) of iron supplementation. In conclusion, the iron hypothesis may help us progress in the understanding of pathophysiological links between ADHD, RLS, and TS, suggesting that iron supplementation might be effective for all these three impairing conditions.