Deficits in Brain's Reward System Observed in ADHD Patients

A brain-imaging study conducted at Brookhaven National Laboratory provides the first definitive evidence that patients suffering from attention deficit hyperactivity disorder (ADHD) have lower-than-normal levels of certain proteins essential for experiencing reward
and motivation.

"These deficits in the brain's reward system may help explain clinical symptoms of ADHD, including inattention and reduced motivation, as well as the propensity for complications such as drug abuse and obesity among ADHD patients," says lead author Nora Volkow, director of the National Institute on Drug Abuse and a long-time collaborator on neuroimaging research at Brookhaven Lab.

The study, published in the September 9, 2009, issue of the Journal of the American Medical Association, also has important implications for treatment. "Finding ways to address the underlying reward-system deficit could improve the direct clinical outcome of ADHD, and potentially reduce the likelihood of other negative consequences of this condition," says study co-author Gene-Jack Wang, chair of Brookhaven's medical department.

Prior to this study, it was not clear whether people with ADHD had abnormalities in the brain's dopamine-mediated motivation/reward system. Previous studies were relatively small and may have been complicated by the fact that some ADHD patients had undergone treatments, or had a history of drug abuse or other conditions that can affect the dopamine system.

To strengthen the statistics and control for these factors, the current study looked at 53 adult ADHD patients who had never received treatment and 44 healthy control subjects -- all of whom had been carefully screened to eliminate potentially confounding variables.

The scientists used positron emission tomography (PET) to measure two markers of the dopamine system -- dopamine receptors, to which the chemical messenger binds to propagate the "reward" signal, and dopamine transporters, which take up and recycle excess dopamine after the signal is sent.

Lying in a PET scanner, each patient was injected with a minute amount of a "radiotracer" compound -- a chemical labeled with a radioactive form of carbon and designed to bind specifically to one of the targets. Different tracers were used for each target, and patients were scanned for each at separate times. By detecting the signal from the radiotracers, the PET machine can measure the receptor and transporter locations and concentrations in various parts of the brain.

The results clearly showed that, relative to the healthy control subjects, the ADHD patients had lower levels of dopamine receptors and transporters in the accumbens and midbrain -- two key regions of the brain directly involved in processing motivation and reward. In addition, the measurements of dopamine markers correlated with measures of behavior and clinical observations of ADHD symptoms, such as reduced levels of attention as measured by standard
psychological tests.

"Our findings imply that these deficits in the dopamine reward pathway play a role in the symptoms of inattention in ADHD and could underlie these patients' abnormal responses to reward," Volkow says.

"This pathway plays a key role in reinforcement, motivation, and in learning how to associate various stimuli with rewards," she adds. "Its involvement in ADHD supports the use of interventions to enhance the appeal and relevance of school and work tasks to improve performance.

"Our results also support the continued use of stimulant medications - the most common pharmacological treatment for ADHD -- which have been shown to increase attention to cognitive tasks by elevating brain dopamine," she says.

The findings may also help explain why ADHD patients are more likely than control subjects to develop drug-abuse disorders and conditions such as obesity.

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Developmental, Behavioral Problems May Plague Kids With Asthma

Much of the research surrounding childhood asthma has sought new approaches to managing the disease. However, little was done to address other conditions that often appear along with asthma including depression and Attention Deficit Hyperactivity Disorder (ADHD), which can negatively affect a child's ability to cope.

Research completed at the University of Virginia Children's Hospital asserts that until these extra conditions or "co-morbidities" are addressed, asthma education programs will not be able to help young patients to the fullest. The results will be published in the April 12 issue of The Journal of Developmental and Behavioral Pediatrics.

"We can definitively state that families with asthmatic children not only report higher incidences of ADHD, but also of depression, anxiety and learning disabilities," says Dr. James Blackman, developmental pediatrician at the Kluge Children's Rehabilitation Center at UVa Children's Hospital and lead study author. "If we can manage these co-morbidities, we can better help children with asthma and their families to manage the disease in the healthiest way possible."

Data for the research came from the National Survey of Children's Health 2003, which was obtained from the Centers for Disease Control and Prevention (CDC) National Center for Health Statistics. The survey results came from telephone polls of households with children. Parents who reported that their child had asthma also were asked to report the severity of their children's asthma and any behavior problems. Information was gathered on a total of 102,353 children from ages 0-17 years during 2003-2004. The survey results were analyzed using SUDAAN, specialized software for analyzing clustered data.

The study uncovered depression, anxiety, behavioral problems, and learning disabilities as co-morbidities common among children with asthma. The more severe the child's asthma was, the higher the incidence of these types of problems. More than 10 percent of asthmatic children experienced problems that lasted longer than a year and required counseling or treatment.

What's more, these children often missed ten or more days of school, leading parents and caregivers to worry about their children's healthy academic and emotional development.

"What also is important about this research is that it shows how asthma can lead to psychosocial disadvantages for children in our society," adds Blackman.

While the medical and research establishment should continue to address the societal problems of poverty and poor education, Blackman believes that children with asthma need to receive tailored and precise treatments addressing their physical and mental and developmental health. This could lead to fewer missed days in school and fewer calls home to parents for behavioral and academic problems.


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