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Researchers Examine Brain Circuitry of ADHD

(Feb 1, 2009)

The view that 20th-century kids diagnosed with attention-deficit/hyperactivity disorder (ADHD) are just misbehaving is "antiquated, anachronistic, and wrong," according to Bradley Peterson, MD. His research includes the identification of anatomical abnormalities, including an enlarged hippocampus (Arch Gen Psychiatry 2006;63[7]:795- 807) and abnormal morphology in the frontal cortices in children and adolescents with ADHD (Lancet 2003;362[9397]:1699-1707).

Dr. Peterson believes that stimulant medication, one of the mainstays of ADHD treatment, can actually attenuate the anatomical abnormalities in the brain that underlie ADHD. "We don't know how it changes brain anatomy, but we believe that it is likely through the effects of the medication on activity within nerve cells, which ultimately alters gene expression and the proteins that determine brain structure," he said. "The circuit that we think is really important for controlling motor activity and unwanted impulses runs from the frontal cortex to the basal ganglia, the thalamus, and back to the frontal cortex. ADHD children have prominent abnormalities in the basal ganglia and thalamus that stimulants seem to normalize."

Currently, Dr. Peterson studies the effects of stimulant medication on the neural systems underlying the disorder at NewYork-Presbyterian Hospital/Columbia University Medical Center. Using functional magnetic resonance imaging (fMRI), Dr. Peterson and his colleagues have been able to show that stimulant medication can improve brain function in children with ADHD.

"Children with ADHD taking stimulant medication seem to be normalizing neural systems that either permit or suppress mindwandering," said Dr. Peterson. "When children with ADHD are not taking stimulant medication, they are unable to suppress the mind-wandering circuits – but when they take the stimulant medication, they are able to shut these off."

In addition to anatomical and fMRI methods, two sophisticated MRI techniques are used by Dr. Peterson to study children with ADHD: diffusion tensor imaging, which allows the imaging of nerve fibers, and magnetic resonance spectroscopy, which allows measurement of chemical compounds such as N-acetyl aspartate, a neuronal marker. Dr. Peterson recently co-authored a chapter on the neurobiology of impulsivity and self-regulatory control in children with ADHD (in press).

Margaret Hertzig, MD, reflected on the large number of children treated for ADHD in modern society: "Although criteria for the diagnosis of ADHD are clearly established, the contribution of social factors and expectations is still a somewhat gray area. To determine when these criteria are met still involves considerable clinical judgment." At NewYork-Presbyterian/Weill Cornell Medical Center, she emphasizes the importance of proper diagnosis. "When I teach residents about ADHD, I point out that one of the most important considerations in the differential diagnosis is normal variation. Many ADHD symptoms are extremes of such temperamental attributes as activity level, intensity, distractibility, attention span, and persistence. But when we make the diagnosis of ADHD, these are children who have both these characteristics and impairment in their ability to function in school and with peers and with adults, mostly their parents," said Dr. Hertzig.

Dr. Hertzig lauded the Child and Adolescent Psychiatry Residency Training Program at NewYork-Presbyterian Hospital, affiliated with both Columbia University College of Physicians and Surgeons and Weill Cornell Medical College, for utilizing the resources of both campuses to provide clinical experience and training opportunities for residents in child psychiatry who treat children with ADHD and other disorders. At NewYork-Presbyterian/Weill Cornell, there is an all-purpose child psychiatry clinic; NewYork Presbyterian/ Columbia has subspecialty clinics.

"The fact that we have different approaches to the assessment and treatment of children enriches the experience of residents in important ways. Both approaches are important to the educational training experiences of future child psychiatrists," she said.

Dr. Peterson added that although the current neurobiological concept of ADHD is that it is a brain disorder, the environment is also crucial. For example, prenatal factors, such as smoking during pregnancy, substantially increase the rate of ADHD. Early childhood experience, such as competent and authoritative caregiving, can help modify the expression and severity of this disorder. Having parents who help kids stay on task and attend to activities, provide appropriate stimulating environments, and help them organize their thoughts and behavior are important for these children. That does not mean that ADHD is caused by parental neglect or dysfunction, but the combination of certain styles of upbringing and life experience with a genetic predisposition appears to increase the rates of ADHD.

"Anxiety and depressive disorders may also be comorbid with ADHD," Dr. Hertzig added. "In addition, there is a great deal of overlap and controversy on the question of the relationship between ADHD and the manic, hypomanic, and mood labile states of bipolar disorder."

ADHD is a syndromic designation based on certain sets of observable behaviors. These clusters of symptoms include inattention/distractibility, impulsivity, and hyperactivity. Children may have symptoms that are primarily one or the other of these types or a combination of both inattention/distractibility and impulsivity/hyperactivity.

Contributing faculty for this article: Margaret Hertzig, MD, and Bradley Peterson, MD

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