Role of Oxidative Stress and Novel Insights in Therapies for Attention-Deficit/ Hyperactivity Disorder (ADHD)

Attention-deficit/hyperactivity disorder (ADHD) is a multiple symptom disorder, primarily of the young. It is diagnosed by signs and symptoms and its diagnosed incidence is increasing in the U.S. and worldwide. Its causation is incompletely understood, but surely multifactorial, and its treatment by pharmaceuticals and counseling is often problematic. I propose that to find a solution to this dilemma requires new thinking resulting in new actions in three areas: (1) ADHD definition/diagnosis, (2) its causation, and (3) its treatment. Regarding ADHD causation, I provide evidence for a new proposal for the involvement of oxidative stress. Indoleamine 2,3-dioxygenase (IDO1), with a hand in every pot, regulates the production of several metabolites that control relevant brain functions. This rate-limiting enzyme of the kynurenine pathway in the brain produces a large number of metabolites that both promote and retard oxidant stress, and also regulates via non-enzymatic functions involving Fe 2+ via oxidant stress mechanisms. Solutions for ADHD by scientific and medical community for more than a century have been limited, not for lack of trying, but because the problems arise in all three areas listed above, and each area is compound. For difficult problems, the first step towards solution is recognition. Currently, we are at the open doorway of applying artificial intelligence (AI) to scientific and medical problems. I propose that AI, by comprehensively assessing the literature on AI and by the ability to generate hypotheses, offers new hope that the hard work of finding solutions for the three stated areas relative to ADHD is achievable. In this perspective minireview I provide new insights for the role of oxidant stress and IDO1 in ADHD. I propose that AI should be applied to evaluate the oxidant stress hypothesis. I also propose initiation of an official process of organized cooperation among leading scientists and treating physicians, with appropriate funding, to incorporate AI fully to solve the problems and provide solutions for causation and treatment of ADHD.