Blood manganese levels in relation to comorbid behavioral and emotional problems in children with attention-deficit/hyperactivity disorder

Patients with attention-deficit/hyperactivity disorder (ADHD) appear to be more vulnerable to the development of other psychiatric disorders than the general population. The proposed neurotoxic mechanisms of manganese involve striatal dopamine neurotransmission, implicated in the pathophysiology of ADHD. We investigated whether the adverse impact of manganese is particularly pronounced in children with ADHD. Blood manganese concentration and diagnosis of ADHD were assessed in a general population of 890 children, aged 8-11 years. The main outcome measure was the Child Behavior Checklist (CBCL). A significant interaction was found between ADHD status and blood manganese level in predicting CBCL total problems score as well as anxiety/depression, social problems, delinquent behavior, aggressive behavior, internalizing problems, and externalizing problems. The directions of the interactions indicated that blood manganese level was more positively correlated with CBCL scores in ADHD children than in the healthy population. In ADHD children, only the fifth quintile of blood manganese concentration was significantly associated with the CBCL total problems score. ADHD children may be more vulnerable than the general school-age population to the neurotoxic effects of manganese exposure, which lead to an elevated risk of developing comorbid mental conditions.