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Reuters, 11/29/04

BRAIN ABNORMALITY LINKED TO HYPERACTIVITY DISORDER

CHICAGO -- Brain scans of children with attention deficit hyperactivity disorder show abnormalities in the fiber pathways along which brain signals pass, scientists said on Monday.

The finding indicates the disorder may be more than just a chemical imbalance, they added.

Using an imaging technique called diffusion tensor imaging, researchers found subtle anatomical differences in children diagnosed with ADHD that may affect communication between key areas of the brain -- the frontal cortex, basal ganglia, brain stem and cerebellum.

"These areas are involved in the process that regulate attention, impulsive behavior, motor activity, and inhibition -- the key symptoms in ADHD children," said lead researcher Manzar Ashtari, an associate professor of radiology and psychiatry at North Shore-Long Island Jewish Health System in New Hyde Park, New York.

In another study, Ashtari found the brain irregularities diminished in children who had been medicated with stimulant drugs for an average of two and a half years.

"The findings ... indicate that the therapeutic effect of stimulants may involve a brain normalization process," said co-researcher Sanjiv Kumra, a psychiatrist at Zucker Hillside Hospital in Glen Oaks, New York.

"Typically, ADHD is described as a chemical imbalance, but our research has shown that there may also be subtle anatomical differences in areas of the brain that are important in this disorder," Kumra said.

Between 3 percent and 5 percent of American children are diagnosed with ADHD. Millions take stimulants to counteract the behavior, which can be disruptive both at home and in school and can lead to problems later in life.

The research was presented at the annual meeting of the Radiological Society of North America.

Copyright Reuters 2004

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American Medical News, 12/20/04

BRAIN SCANS MAY DETECT MARKERS
OF SOME MENTAL DISORDERS

Imaging could provide a biological basis for ADHD and bipolar disorder, but it is too soon to become a part of clinical practice.

by Victoria Stagg Elliott

In the early days of his career, John D. Port, MD, PhD, worked with a psychiatrist who suggested he go into radiology and develop tests to make it easier to pin down a diagnosis of mental illness.

"Psychiatry is really one of the last frontiers of medicine where you don't have a blood test," said Dr. Port, assistant professor of radiology and consultant at the Mayo Clinic in Rochester, Minn.

Now, if his recent efforts pan out, the wish of his mentor and that of many physicians who work with mentally ill patients may be fulfilled -- at least in terms of bipolar disorder.

This diagnosis, in particular, can be tricky to nail down.

According to a patient advocacy group, the Depression and Bipolar Support Alliance, most people with bipolar disorder have symptoms for a decade and see an average of four doctors before being diagnosed.

Dr. Port and his research team used magnetic resonance spectroscopy to compare the brains of 19 bipolar disorder patients who were not on any medication to the brains of healthy controls.

According to study findings presented at last month's Radiological Society of North America annual meeting in Chicago, magnetic resonance spectroscopy detected striking differences in the metabolites of four areas of the brains of those with bipolar disorder.

Dr. Port suggested that these markers could eventually be used to diagnose the condition.

"The psychiatric community clearly needs a tool to help diagnose bipolar disorder," said Dr. Port.

"We are hopeful that very high-field MR spectroscopy will prove helpful by identifying metabolic markers of the disease," Dr. Port added

Potential to unlock ADHD clues

Imaging may also offer insights that will aid in the diagnosis of other illnesses of the brain. Two papers presented at RSNA's annual meeting, for instance, suggested scanning could detect differences in the brains of children with attention-deficit/hyperactivity disorder and that usual treatment approaches seemed to address the problem directly.

In the first paper, researchers used diffusion tensor imaging to compare the brains of 18 children with ADHD to 15 normal controls. The scans detected a disruption in the cabling that connects the cerebellum to the frontal lobe in ADHD children. The second study compared the brains of 10 children with ADHD on medication to another 10 with ADHD but who were not being treated with any drugs. This paper found that stimulants seemed to correct the disruption.

"Typically ADHD is described as a chemical imbalance, but our research has shown that there may also be subtle anatomical differences in areas of the brain that are important in this disorder," said co-principal investigator Sanjiv Kumra, MD, a psychiatrist at the Zucker Hillside Hospital in Glen Oaks, N.Y.

There is hope that studies like these might reduce the stigma associated with ADHD, bipolar disorder and other mental illnesses by proving the biological basis underlying these conditions.

"Psychiatrists have long assumed that there were biological bases for many of the disorders that we treat, and it is encouraging and exciting to see that recent research confirms these beliefs," said David Fassler, MD, clinical associate professor of psychiatry at the University of Vermont College of Medicine in Burlington.

Researchers noted, though, that these scans were not ready for regular use. Experts agreed.

"It is absolutely not time for parents to be taking their children in for scans," said Manzar Ashtari, PhD, who presented the ADHD papers at the meeting. Dr. Ashtari is an associate professor of radiology and psychiatry at North Shore-Long Island Jewish Health System in New Hyde Park, N.Y.

Here and now

For the moment, most believe that these tools may make subject selection for trials more reliable and lead researchers to new drug targets and more tailored treatment.

"I could see more radiologic studies helping us understand which specific chemicals may help certain people. Having spent all the years that I have [treating ADHD], I still can't tell who is more likely to respond to what or not respond well to anything," said Susan Louisa Montauk, MD, professor of family medicine at the University of Cincinnati. She is also the medical director of the Affinity Center, which specializes in the care of adults and children with attention-deficit and related disorders.

Critics charged, however, that these studies were too small to draw any conclusions beyond that of the need for additional research. In the case of the ADHD papers, experts expressed concern that the findings could be confounded by other conditions such as oppositional defiant disorder or mood disorders that are particularly common for these children.

"The sample size was small," said Michael Wasserman, MD, a general pediatrician at Ochsner Clinic Foundation in New Orleans. "And how did they distinguish children who didn't have comorbid conditions?"

Some physicians also worried that these tests might add too much to the cost of the process of getting a diagnosis without providing much benefit. In the case of ADHD, some physicians said that history-taking and current questionnaires used for detecting cases were sufficient.

"It's not that hard to make a diagnosis [of ADHD]," said Thomas Bent, MD, associate clinical professor of family medicine at the University of California, Irvine. "We already have a lot of good studies that show that the tools we have have good sensitivity and specificity, and we could be spending a lot of money on a procedure that could be uncomfortable and frightening to the child."

SOURCES:

"Diffusion Tensor Imaging of Children with Attention Deficit/Hyperactivity Disorder," abstract, presented at the Radiological Society of North America's annual meeting, Nov. 28-Dec. 3 (rsna2004.rsna.org/rsna2004/V2004/conference/event_display.cfm?em_id=4411963)

"Stimulant Medications and Brain Normalization Effect in Treated ADHD Patients: A Preliminary Diffusion Tensor Imaging Study," abstract, presented at the Radiological Society of North America's annual meeting, Nov. 28-Dec. 3 (rsna2004.rsna.org/rsna2004/V2004/conference/event_display.cfm?em_id=4414822)

"Imaging Markers of Bipolar Disease: Evaluation of Proton Magnetic Resonance Spectroscopic Imaging at 3T," abstract, presented at the Radiological Society of North America's annual meeting, Nov. 28-Dec. 3 (rsna2004.rsna.org/rsna2004/V2004/conference/event_display.cfm?em_id=4411606)

Copyright 2004 American Medical Association

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