Brain Iron Levels a Potential ADHD Biomarker

Megan Brooks

June 17, 2014

Children with attention-deficit/hyperactivity disorder (ADHD) have reduced iron levels in the brain, which normalize with stimulant medication, new research suggests.

Investigators at the Medical University of South Carolina Center for Biomedical Imaging in Charleston found that medication-naive patients with ADHD had significantly lower brain iron levels compared with their counterparts who had been receiving psychostimulant medication.

The researchers also found that ADHD patients with a history of psychostimulant medication treatment had brain iron levels comparable with those of control individuals, suggesting that brain iron levels may increase to normal levels with psychostimulant treatment.

These findings have potential implications for diagnosis and treatment of ADHD, lead researcher Vitria Adisetiyo, PhD, told Medscape Medical News.

"Currently, ADHD diagnosis is based solely on behavioral questionnaires and clinical semistructured interviews with parents and the child," she explained. "If our findings of significantly lower brain iron in medication-naive ADHD patients are confirmed in a larger study, then lower brain iron may serve as a physiological biomarker for ADHD that can help inform clinical diagnosis, particularly in borderline cases," she added.

"If longitudinal studies of ADHD patients, before and after taking psychostimulant medications, confirm that brain iron levels do indeed normalize with psychostimulant medication, then this biomarker could also be used to help monitor the effectiveness of medication treatment," Dr. Adisetiyo said.

The study was published online June 17 in Radiology.

New Diagnostic Tool

The study included 27 healthy control participants and 22 patients with ADHD ― 12 who had never taken stimulant medication, and 10 with a history of stimulant use ― aged 8 to 18 years. The groups did not differ significantly with respect to age, sex distribution, IQ, or ethnicity.

On magnetic field correlation (MFC) imaging, medication-naive ADHD patients had significantly lower striatal and thalamic MFC indexes of brain iron than control participants and medicated ADHD patients.

Medicated ADHD patients had brain iron levels comparable with healthy control individuals, suggesting that brain iron may increase to normal levels with psychostimulant treatment, the researchers note.

Because there were no between-group differences in blood iron levels, "our research suggests that iron absorption into the brain may be abnormal in ADHD," Dr. Adisetiyo said in a statement.

Dr. Adisetiyo added that it is possible that brain imaging could aid in diagnosis of ADHD in borderline cases.

"If future studies pan out, measuring brain iron with advanced MRI methods such as magnetic field correlation imaging could be done routinely, as the acquisition time is clinically feasible (~7 minutes) and requires minimal postprocessing. Another advantage is that measuring brain iron with MRI does not require any contrast agent or radioactive label injections ― this is very important, given ADHD largely effects a pediatric population," she said.

Important Message for Parents

Naomi Steiner, MD, pediatrician and ADHD researcher with the Floating Hospital for Children at Tufts Medical Center in Boston, Massachusetts, who was not involved in the study, said, "It should be made clear that there were no differences between groups in serum iron indices. This is important because we do not want parents supplementing their children with iron. Iron supplementation should be supervised by a clinician, and in too large quantities can be toxic."

"This study brings us forward into thinking about the possible links between clinical presentation of ADHD and what might be going on in the brain," she added.

A "few concerns" regarding the study include the fact that there are more girls than boys in the control group, she said. "I understand that they noted this difference is not statistically significant, but it is a small group. I do wonder why this occurred, as it was probably not necessary from an enrollment perspective, and this might affect results one way or another," Dr. Steiner commented.

She also wondered about including children who had a history of stimulant use in the medicated group. In her view, "it would have been much cleaner with such a small sample size to have medication-naive participants compared to participants currently on stimulant medication."

As for diagnosing ADHD with MRI, Dr. Steiner said that if brain iron differences do correlate with the clinical picture, "it is still easier and much less expensive to ask a parent and teacher to fill out a questionnaire, and, yes, even in the 21st century, for a trained clinician to talk to the parent and child."

"On the other hand, this does not take away from the interest in continued research to enhance our understanding on how our brains work and how we might be able to better tailor therapies in the future, depending on brain biomarkers," said Dr. Steiner.

Dr. Adisetiyo and colleagues are currently recruiting a larger study cohort in an attempt to replicate these findings and have plans to conduct a larger longitudinal study looking at brain iron levels before and after use of psychostimulant medication in children and adolescents with ADHD.

The study was supported by the National Institutes of Health. The authors and Dr. Steiner report no relevant financial relationships.

Radiology. Published online June 17, 2014. Abstract

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