MRI technique may help prevent ADHD misdiagnosis

This shows subgroup averages of parametric maps of MRI brain iron indices: magnetic field correlation (MFC: top row) and relaxation rates R2 (second row), R2*(third row), and R2' (bottom row). 

Parametric maps, masked for regions of interests (green): caudate nucleus (CN), putamen (PUT), globus pallidus (GP) and thalamus (THL), are shown for controls (n = 27), medication-naïve ADHD patients (ADHD-non-medicated; n = 12) and ADHD patients with a history of psychostimulant treatment (ADHD-medicated; n = 10). 

The ADHD-non-medicated subgroup displayed significantly reduced striatal (CN, PUT) and thalamic MFC compared to both controls and the ADHD-medicated subgroup. 

No significant differences were detected between the latter two groups. 

Credit: Radiological Society of North America 

Brain iron levels offer a potential biomarker in the diagnosis of attention deficit hyperactivity disorder (ADHD) and may help physicians and parents make better informed treatment decisions, according to new research published online in the journal Radiology.

ADHD is a common disorder in children and adolescents that can continue into adulthood. Symptoms include hyperactivity and difficulty staying focused, paying attention and controlling behavior. The American Psychiatric Association reports that ADHD affects 3 to 7 percent of school-age children.

Psychostimulant medications such as Ritalin are among the drugs commonly used to reduce ADHD symptoms.

Psychostimulants affect levels of dopamine, a neurotransmitter in the brain associated with addiction.

"Much debate and concern has emerged regarding the continual rise of ADHD diagnosis in the U.S. given that two-thirds of those diagnosed receive psychostimulant medications," said Vitria Adisetiyo, Ph.D., postdoctoral research fellow at the Medical University of South Carolina in Charleston, S.C.

"We wanted to see if we could identify brain iron as a potential noninvasive biomarker for medication-naïve ADHD to prevent misdiagnosis."

For the study, the research team measured brain iron levels in 22 children and adolescents with ADHD, 12 of whom had never been on medication for their condition (medication naïve), and 27 healthy control children and adolescents using a magnetic resonance imaging (MRI) technique called magnetic field correlation imaging.


The technique was introduced in 2006 by study co-authors and faculty members Joseph A. Helpern, Ph.D., and Jens H. Jensen, Ph.D. No contrast agents were used, and blood iron levels in the body were measured using a blood draw.

The results showed that the 12 ADHD medication-naïve patients had significantly lower brain iron levels than the 10 ADHD patients who had been on psychostimulant medication and the 27 children and adolescents in the control group.

In contrast, ADHD patients with a history of psychostimulant medication treatment had brain iron levels comparable to controls, suggesting that brain iron may increase to normal levels with psychostimulant treatment.

"Our research suggests that iron absorption into the brain may be abnormal in ADHD given that atypical brain iron levels are found even when blood iron levels in the body are normal," Dr. Adisetiyo said.

"We found no differences in blood iron measures between controls, medication-naïve ADHD patients or pscyhostimulant-medicated ADHD patients."

If the results can be replicated in larger studies, magnetic field correlation might have a future role in determining which patients would benefit from psychostimulants—an important consideration because the drugs can become addictive if taken inappropriately and lead to abuse of other drugs like cocaine.

"We want the public to know that progress is being made in identifying potential noninvasive biological biomarkers of ADHD which may help to prevent misdiagnosis," Dr. Adisetiyo said.

"We are currently testing our findings in a larger cohort to confirm that measuring brain iron levels in ADHD is indeed a reliable and clinically feasible biomarker."

More information: "Multimodal MR Imaging of Brain Iron in Attention Deficit Hyperactivity Disorder: A Non-invasive Biomarker that Responds to Psychostimulant Treatment?" Radiology, 2014.

Restless Legs Syndrome (RLS), Insomnia and Brain Chemistry

Johns Hopkins researchers believe they may have discovered an explanation for the sleepless nights associated with Restless Legs Syndrome (RLS), a symptom that persists even when the disruptive, overwhelming nocturnal urge to move the legs is treated successfully with medication.

Neurologists have long believed RLS is related to a dysfunction in the way the brain uses the neurotransmitter dopamine, a chemical used by brain cells to communicate and produce smooth, purposeful muscle activity and movement.

Disruption of these neurochemical signals, characteristic of Parkinson's disease, frequently results in involuntary movements.

Drugs that increase dopamine levels are mainstay treatments for RLS, but studies have shown they don't significantly improve sleep. An estimated 5 percent of the U.S. population has RLS.

Richard P. Allen

The small new study, headed by Richard P. Allen, Ph.D., an associate professor of neurology at the Johns Hopkins University School of Medicine, used MRI to image the brain and found glutamate—a neurotransmitter involved in arousal—in abnormally high levels in people with RLS.

The more glutamate the researchers found in the brains of those with RLS, the worse their sleep. The findings are published in the May issue of the journal Neurology.

"We may have solved the mystery of why getting rid of patients' urge to move their legs doesn't improve their sleep," Allen says.

"We may have been looking at the wrong thing all along, or we may find that both dopamine and glutamate pathways play a role in RLS."

For the study, Allen and his colleagues examined MRI images and recorded glutamate activity in the thalamus, the part of the brain involved with the regulation of consciousness, sleep and alertness.

They looked at images of 28 people with RLS and 20 people without. The RLS patients included in the study had symptoms six to seven nights a week persisting for at least six months, with an average of 20 involuntary movements a night or more.

The researchers then conducted two-day sleep studies in the same individuals to measure how much rest each person was getting.

In those with RLS, they found that the higher the glutamate level in the thalamus, the less sleep the subject got.

They found no such association in the control group without RLS. Previous studies have shown that even though RLS patients average less than 5.5 hours of sleep per night, they rarely report problems with excessive daytime sleepiness.

Allen says the lack of daytime sleepiness is likely related to the role of glutamate, too much of which can put the brain in a state of hyperarousal, day or night.

If confirmed, the study's results may change the way RLS is treated, Allen says, potentially erasing the sleepless nights that are the worst side effect of the condition.

Dopamine-related drugs currently used in RLS do work, but many patients eventually lose the drug benefit and require ever higher doses.

When the doses get too high, the medication actually can make the symptoms much worse than before treatment.

Scientists don't fully understand why drugs that increase the amount of dopamine in the brain would work to calm the uncontrollable leg movement of RLS.

Allen says there are already drugs on the market, such as the anticonvulsive gabapentin enacarbil, that can reduce glutamate levels in the brain, but they have not been given as a first-line treatment for RLS patients.

RLS wreaks havoc on sleep because lying down and trying to relax activates the symptoms. Most people with RLS have difficulty falling asleep and staying asleep.

Only getting up and moving around typically relieves the discomfort. The sensations range in severity from uncomfortable, to irritating, to downright painful.

"It's exciting to see something totally new in the field—something that really makes sense for the biology of arousal and sleep," Allen says.

As more is understood about this neurobiology, the findings may not only apply to RLS, he says, but also to some forms of insomnia.

ADHD: Brain scans reveal drugs' effects on attention

Scientists have developed a way to use PET scans to test if drugs are helping mice that have been genetically engineered to have a form of attention deficit.

In the brain of the altered mouse (right), low dopamine levels result in a brighter image. 

(Credit: David Gutmann, MD, PhD)

Scientists have developed a way to evaluate new treatments for some forms of attention deficit disorder.

Working in mice, researchers at Washington University School of Medicine in St. Louis showed that they can use brain scans to quickly test whether drugs increase levels of a brain chemical known as dopamine.

In a study published last year, the same group found that raising dopamine levels in mice alleviates attention deficits caused by neurofibromatosis type 1 (NF1), a condition that affects more than 100,000 people in the United States. Approximately 60 percent to 80 percent of children with NF1 have some type of attention deficit problem.

"Many kids with NF1 really struggle in school, and finding ways to help alleviate attention problems is a high priority," says David H. Gutmann, MD, PhD, the Donald O. Schnuck Family Professor of Neurology.

"The technique we've refined may make it possible to match specific treatments to the patients with NF1 and attention deficit who are most likely to benefit from those treatments."

The results appear online in Experimental Neurology.

Symptoms of NF1-related attention deficits are similar to those that affect children in the general population. But it's unclear whether the brain changes that underlie these problems in children with NF1 are similar to the brain changes that cause attention deficits in the general population.

"This mouse model may not be a perfect model for all forms of attention deficit, but it is a terrific model for one type of attention system dysfunction," Gutmann says. "Greater understanding of what goes wrong in some children with NF1 could lead to new insights into a broader variety of attention problems."

Gutmann is director of the Washington University Neurofibromatosis (NF) Center, a national referral center for patients with all forms of neurofibromatosis. The center is active in basic science research and clinical trials, with the goal of developing innovative new approaches for treating patients with NF.

Gutmann and his colleagues have developed genetically engineered mice that develop NF1-related attention problems and brain tumours.

Last year, Gutmann showed that one of these lines of mice had lower levels of dopamine in part of the brain. Following treatment with the drug Ritalin, both the brain dopamine levels and the attention deficits in these mice were restored to normal.

"Prior to our study, there was no molecular basis for using Ritalin to treat children with NF1 and attention deficits, so its use depended on the pediatrician's practice, the severity of the attention deficit and how comfortable the parents were with the use of medication," Gutmann says.

"In general, only the most severely affected kids are being treated, but that may change in the future."

Read more at Science Daily

Research Claims Ritalin Improves Ability to Learn

Research Claims Ritalin Improves Ability to Learn

Ritalin (methylphenidate), a drug prescribed for millions of children who have attention deficit hyperactivity disorder (ADHD), appears to improve the ability to learn by enhancing the speed of learning. Currently, Ritalin is prescribed to help inhibit impulsive behaviour, which in turn can improve a child’s ability to focus on tasks.

The new finding is the result of research by investigators at the University of California, San Francisco (UCSF). It is significant because it lets scientists know that Ritalin impacts and improves behaviour through two specific types of neurotransmitter receptors rather than just one. Neurotransmitters are chemicals that act as messengers to allow neurons to communicate with each other.

Previously experts knew that Ritalin enhanced the activity of the neurotransmitter dopamine receptor known as D2, which controls the ability to stay focused on a task. The new research shows that another dopamine receptor called D1, which is involved in the ability to learn and learning efficiency, is also affected by Ritalin. Apparently the drug produces these benefits by strengthening the ability of the neurons to communicate with each other at their meeting points, called synapses.

These new findings may allow researchers to develop more efficient drugs to treat ADHD and to improve the ability to focus and learn more efficiently, according to Antonello Bonci, MD, principal investigator at the Ernest Gallo Clinic and Research Center and professor of neurology at UCSF.