This is a story about iron: What does it do in the brain, and why should someone with attention-deficit/hyperactivity disorder (ADHD) care?
ADHD is a common neurodevelopmental disorder in school-age children and adolescents. The disorder is characterized by inattention, impulsivity, and hyperactivity. It can cause individuals to have significant challenges with everyday tasks and social interactions.
In my opinion, as a neuroscientist who specializes in brain chemistry, the underlying cause of such a complex psychiatric condition should never be distilled into the dysfunction of a single neurotransmitter system. For example, neuroscientists now realize that psychosis is not a problem with the health of dopamine neurons and that depression has very little to do with serotonin neuronal activity. (To learn more, click here.) Gross oversimplifications of the underlying mechanisms of these disorders have greatly slowed the discovery of effective therapies for them.
With these cautions in mind, let’s examine the role of iron in the function of dopamine neurons in the brains of children with ADHD.
Reduced activity of the brain’s dopamine neurons is thought to play a significant role in the pathophysiology of ADHD. This is why psychostimulants that increase the activity of dopamine neurons, and the subsequent release of dopamine within a small number of brain regions, have become the primary treatment for ADHD symptoms. The existing logic supporting this conclusion is that if increasing dopamine release reduces symptoms, then the symptoms of ADHD are due to too little release of dopamine somewhere in the brain.
Are ADHD meds that increase the release of dopamine from dopamine neuronal terminals effective?
Yes, ADHD medications are effective, usually within the first hour after taking the drugs, in reducing core symptoms like inattention, hyperactivity, and impulsivity, improving focus, behavior, and daily functioning (Parlatini et al., 2024).
How does iron play a role?
Brain iron found inside dopamine neurons controls the enzyme that leads to the synthesis of dopamine. It’s considered the rate-limiting step. People with iron‑deficiency anemia who do not absorb enough iron from their diet do not produce adequate amounts of dopamine. If the deficiency is severe, anemics may experience reduced motivation, poor concentration, and mood changes typical of someone with reduced dopamine production. As expected, in the brain, iron levels are high in regions that contain lots of dopamine neurons. New magnetic resonance imaging (MRI) techniques can provide estimates of brain iron levels. Under normal circumstances, the iron content of dopamine-rich brain regions rapidly increases throughout childhood and adolescence and is associated with the maturation of dopamine neurons.
Medication-naïve children with ADHD have lower brain iron content. MRI studies show that ADHD children given psychostimulants have higher brain iron content than medication-naïve children with ADHD. Furthermore, their brain iron content was similar to that of neurotypical children without ADHD. In addition, longer duration of psychostimulant treatment was associated with higher levels of iron. The elevated levels of iron have a functional consequence. Recent neuroimaging studies have shown that long-term treatment with standard psychostimulants directly increases dopamine function in the brain of children with ADHD (Kaminski et al., 2024).
When should children start taking these meds?
A recent study investigated the effect of age at treatment onset on increases in brain iron content and its impact on the function of dopamine neurons in patients with ADHD. There were two interesting discoveries: The duration of the treatment did not significantly affect brain iron level but the age of onset of therapy had a major impact on outcome. Children with ADHD who started psychostimulant therapy at 8, or earlier, showed significantly higher iron content in brain regions that have the highest levels of dopamine function, as compared to children with ADHD who started psychostimulant treatment at the age of 9 or later.
Summary
Medication-naïve children with ADHD have lower brain iron content, as compared to normal aged children. ADHD children medicated with standard psychostimulant therapy displayed the same level of brain iron as peers without ADHD. Starting psychostimulant treatment earlier, rather than later, was associated with more brain iron and, according to MRI studies, increased dopamine function. Important caveat: Psychostimulants are not considered a cure for ADHD; it is unknown whether iron levels would decline if the patients discontinued drug therapy.
