Serum manganese concentrations in children with attention deficit/hyperactivity disorder: A systematic review

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in childhood, with both genetic predispositions and environmental toxic exposures playing a role in its etiology. In recent years, increasing attention has been directed toward manganese (Mn), an environmental neurotoxicant, due to its potential impact on children's neurodevelopment. Manganese may affect the dopaminergic system, which is known to be closely associated with the pathophysiology of ADHD. This thesis aimed to systematically review studies that evaluated manganese levels in children diagnosed with ADHD. A systematic literature search was conducted in PubMed, Scopus, Science Direct, and Web of Science databases. The study selection process was structured based on the PRISMA guidelines, and a total of 30 eligible studies were included in this systematic review. The included studies were analyzed in terms of diagnostic criteria (DSM-IV, DSM-V, ICD-10), types of biological samples (blood, hair, urine, saliva, teeth, etc.), and analytical methods used for manganese measurement (AAS, ICP-MS, XRF, etc.). The methodological quality and risk of bias were assessed using the critical appraisal checklists developed by the Joanna Briggs Institute. The analysis revealed that both elevated and reduced manganese levels may be associated with an increased risk of ADHD in children. These findings suggest a potential U-shaped relationship, indicating that both manganese deficiency and excess could have neurotoxic effects on neurodevelopment. However, due to variations in sample sizes, lack of control groups in some studies, and heterogeneity in measurement methods, the findings should be interpreted with caution, and causal inferences cannot be definitively established. Keywords: ADHD, Manganese, Manganese Toxicity