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ADHD: Brain Iron May Be Marker

— CHICAGO -- Low Fe levels in the brain may signal the presence of attention-deficit/hyperactivity disorder (ADHD), researchers reported here.

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CHICAGO -- Low Fe levels in the brain may signal the presence of attention-deficit/hyperactivity disorder (ADHD), researchers reported here.

In a small study of children and adolescents with ADHD, those who'd never taken any drugs for their condition had significantly lower levels of brain iron as seen on magnetic correlation field (MFC) imaging compared with controls and with those being treated with drugs for the condition, according to Vitria Adisetiyo, PhD, of the Medical University of South Carolina, and colleagues.

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  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

They reported their findings at the here.

ADHD is currently based on a subjective diagnosis. Having a biomarker to confirm that diagnosis could increase clinician and patient confidence in the diagnosis, Adisetiyo said.

"It would be beneficial when the psychiatrist is less confident of a diagnosis, if you could put a patient in a scanner for 15 minutes and confirm that brain iron is low," she said in a statement.

A better diagnosis could also help diminish the likelihood of addiction to the psychostimulant medications used to treat the condition, Adisetiyo added.

Researchers have been searching for , including genetic susceptibility, but few studies have looked at brain iron. One flawed study didn't account for previous use of stimulant medication, which likely confounded the results, Adisetiyo said.

She explained that there's a fundamental relationship between brain iron and dopamine, the neurotransmitter that is a key target of stimulant drugs for the condition. Iron is required for dopamine synthesis and regulation, and dopamine has been shown to be sensitive to changes in brain iron -- most recently in a study of restless legs syndrome, she said.

Thus, brain iron may be a reflection of dopamine levels and could offer insight into the diagnosis of ADHD. So the researchers hypothesized that they would see reduced iron levels in the brains of medication-naive ADHD patients.

They studied 27 healthy controls and 22 patients with ADHD: 10 of the ADHD patients had current or past use of psychostimulant drugs, while 12 were medication-naive. All of them had a fasting blood draw to confirm serum iron levels.

The researchers performed both MCF imaging and the more traditional MRI transverse relaxation rate imaging, and they focused on four central areas of the brain most impacted by ADHD: the globus pallidus, thalamus, putamen, and caudate nucleus.

With the MFC scan, Adisetiyo and colleagues found significantly lower levels of brain iron in ADHD patients who weren't medicated than in normal controls or those being treated with medications.

In statistical analyses that looked at the four brain regions individually, there were significantly lower levels of brain iron in medication-naive patients than in controls or drug-treated patients for three of those regions: the putamen, caudate nucleus, and thalamus. There were also differences in brain iron levels for the globus pallidus, but they were not significant.

Adisetiyo added that the traditional relaxation scans didn't detect differences in brain iron levels, and that this wasn't unexpected because MRI relaxation scans are not as specific as MFC scans.

She concluded that measuring brain iron levels with MFC may offer a noninvasive diagnostic biomarker that can be used to confirm diagnosis and medication prescription for ADHD patients.

The work also suggests that there's an abnormality in iron uptake in the brain with ADHD. Just giving iron supplements alone is unlikely to resolve symptoms, Adisetiyo said, because most of the kids in the study had normal serum levels of the element.

"It may be a problem with absorption in the brain [specifically]," she said. "It suggests iron supplementation is not the route to go."

, chief of neuroradiology at the University of Virginia, who was not involved in the study, said the technique would be especially beneficial in this young population, since it doesn't require contrast agents and uses non-ionizing radiation.

He added that it would also be reassuring to have some biomarker to give clinicians and patients and their families confidence in the diagnosis.

"There's a treatment, but it has side effects, so it's something you would like to be able to be sure of in your diagnosis," Wintermark told 51˶. "If it was possible to identify a specific biomarker that would be reliable for diagnosis and that could be used to monitor the treatment, that would be great."

Disclosures

Adisetiyo reported no conflicts of interest. A co-author reported relationships with Siemens.

Primary Source

Radiological Society of North America

Source Reference: Adisetiyo V, et al "Medication-naive attention-deficit/hyperactivity disorder patients have low brain iron levels as detected by magnetic field correlation imaging" RSNA 2013; Abstract SSE21-06.