Researchers analyzed MRI data from children with attention deficit hyperactivity disorder (ADHD) and found that the age at which psychostimulant use begins may be linked to iron content in certain brain regions. The work was published in the journal Brain Research.
ADHD is a developmental disorder manifested by inattention, impulsivity and hyperactivity. It is associated with reduced signaling of dopamine, a chemical messenger that regulates movement, attention and the reward system. Doctors often prescribe psychostimulants that increase the availability of dopamine in the central nervous system.
Iron is needed for dopamine synthesis: the enzyme tyrosine hydroxylase, which is responsible for its production, does not work without iron. Iron also participates in the formation of myelin, the protective sheath of nerve fibers that speeds up signal transmission. It therefore accumulates in dopamine-rich zones such as the basal ganglia and the substantia nigra, deep brain structures important for movement control and learning.
It was previously noted that children with ADHD who did not take medication often have lower brain iron levels than peers without the disorder, while in those receiving psychostimulants it is closer to normal. This raised the question of whether treatment affects iron content.
A group led by Hugo A. E. Morandini of the Child and Adolescent Health Service in Perth, Australia, examined data from the Oregon ADHD-1000 project. The analysis included 29 children with ADHD who regularly took psychostimulants and 38 children without psychiatric diagnoses. All underwent MRI at the start of the study and two years later; iron concentration in tissues was assessed by their magnetic properties.
No statistically significant differences were found in the substantia nigra, thalamus and most parts of the basal ganglia between the groups. However, children with ADHD had less iron in the globus pallidus, a basal ganglia structure involved in regulating dopamine circuits and reward-related behavior. The authors suggested this may be linked to the shorter average duration of medication use in their sample compared with previous studies.
The researchers then focused on the children with ADHD. Duration of therapy was almost unrelated to iron content: only a very weak negative association was found for the thalamus, but it is unlikely to have clinical significance. Age at treatment start showed a different picture. The children were divided into those who began taking medication at age eight or earlier and those who began at age nine or later. In those who started earlier, iron content was higher in the thalamus, caudate nucleus, putamen and globus pallidus. The researchers suggested that early treatment initiation may coincide with periods of active development of iron and dopamine systems, making the dopamine system more sensitive to external influences.
The work has limitations. The sample was small, so the results require confirmation in larger groups. Data on treatment start and duration relied on parents' recollections, which may be inaccurate. There was no information on exact doses or strictness of adherence to the regimen. Because the scientists observed existing practice rather than prescribing treatment, the results indicate a statistical association rather than causation. It is possible that children who are prescribed medication earlier have more severe symptoms linked to baseline differences in brain biology. Iron levels before treatment began could not be measured, so isolating a direct effect of the drugs is difficult.
Further studies should follow patients from before treatment initiation into adulthood to understand whether differences in iron content persist over the years.