Study Evaluates Two Medications For ADHD

University of Illinois at Chicago researchers are comparing two drugs commonly used to treat attention deficit hyperactivity disorder to determine if genetic factors predict which children will respond to either or both drugs.

Many different medications are used to treat ADHD, including stimulants and non-stimulants, says Dr. Mark Stein, principal investigator of the National Institute of Mental Health-funded study and director of the Hyperactivity, Attention, and Learning Problems Clinic at UIC.

“Unfortunately, clinicians are unable to predict in advance who will respond or not respond to a particular medication,” Stein said.

The study will be conducted in Chicago and New York. Stein and colleagues will enroll 160 children and adolescents between ages 7 and 17 in Chicago. Dr. Jeffrey Newcorn of Mt. Sinai School of Medicine heads the New York site.

Participants will undergo psychiatric evaluations, IQ and achievement tests, a blood test, an electrocardiogram and a physical exam. They will then receive several doses of atomoxetine (a non-stimulant medication), melthylphenidate (a stimulant medication), and a placebo, during a carefully monitored blinded dosing sequence to determine their optimal response to each medication.

During the 12 to 15-week study, researchers will assess the children’s ADHD symptoms, social functioning, problem-solving skills and sleep patterns to determine the efficacy and tolerability of each medication.

Previous research conducted by Stein and colleagues found that children with a variant form of a dopamine transporter gene — a variant known to be associated with ADHD — responded poorly to stimulant medication and had more side effects at lower doses. The new study will test whether patients with this genetic marker respond better to non-stimulant medication.

“At the end of the study we hope to be able to look at a child’s biological characteristics to statistically predict who is more likely to respond to a certain medication and to determine who is more likely not to respond or to have a particular side effect,” Stein said.

“The study provides an idealized standard of care in that the children will be carefully evaluated during their treatment with two different medications, with frequent monitoring that typically does not occur during the normal course of ADHD treatment,” said Stein.

At the end of the trial, participants will be referred back to their primary care provider or given a referral for ongoing treatment with information learned from the study.

Popular ADHD Drug Safe And Effective For Pre-schoolers?

A new study by researchers from the Johns Hopkins Children’s Center and five other medical centers concludes that carefully measured, low doses of methylphenidate (Ritalin) are safe and effective for attention-deficit and hyperactivity disorder (ADHD) in preschoolers. Investigators warn, however, that 3- to 5-year-olds appear more sensitive to the drug’s side effects, which include irritability, insomnia and weight loss, than are older children with ADHD and require closer monitoring.

Children who took the drug also experienced somewhat slower growth rates. On average, children on the drug grew half an inch per year less than expected and gained 2.9 pounds less than expected. Researchers recommend that pediatricians weigh the risks of slowed growth rates against the benefits of treatment. Children on long-term treatment with methylphenidate should be monitored carefully several times a year to assess growth changes over time.

Methylphenidate is the most widely prescribed drug for the treatment of ADHD in children but is not approved by the Food and Drug Administration (FDA) for use in children younger than 6.

Results of the federally funded research, the first large-scale, long-term study of the safety and value of the drug in younger children, appear in a special section of the November issue of the Journal of the American Academy of Child and Adolescent Psychiatry.

“These results give us the missing links in the decision to prescribe a drug that’s been widely used off-label in preschool-age children,” says Mark Riddle, M.D., director of Child and Adolescent Psychiatry at the Children’s Center and a co-author on the study, which followed 303 children between 3 and 5 over 70 weeks. “We were able to confirm what many already suspected-that even lower doses in preschoolers can safely achieve the desired therapeutic effect and indeed that low doses are often optimal.”

Children in the study were started on a low-dose regimen of medication ranging from 3.75 mg total daily to 22.5 mg total daily. By comparison, the cumulative daily dose for older children ranges from 15 mg per day to 50 mg per day. The optimal dose needed to reduce symptoms ranged widely in preschool-age children, but on average, 14 mg daily was effective in reining in symptoms.

“One of the surprises was that in some cases, doses as low as even 3 to 4 mg a day were helpful to some preschoolers, which goes to show that lower doses need to be given a chance before higher doses are tried,” Riddle explains.

About 11 percent of those enrolled in the study experienced side effects severe enough to drop out. These included weight loss, anxiety, skin picking, mood disturbances and insomnia.

“We want parents to know that trained professionals can make an accurate diagnosis and prescribe helpful and safe treatment in preschoolers with ADHD,” Riddle says. “But do expect your prescribing physician to monitor side effects closely and regularly and to tweak the dose if necessary.”

ADHD is characterized by a wide range of symptoms, including inability to concentrate, being easily distracted, fidgeting and restlessness, among others. Left untreated, ADHD can interfere with academic progress and social and emotional development. More than 4.4 million children in the United States have ADHD, according to estimates by the Centers for Disease Control and Prevention. About 2 percent of preschool-age children are believed to have ADHD.

Brain Imaging Designs ADHD Treatment With Lower Risk Of Abuse

An article by Thomas J. Spencer, M.D, on a new study in the March 2006 issue of The American Journal of Psychiatry (AJP), the official journal of the American Psychiatric Association (APA), shows how brain imaging is used to identify a form of methylphenidate, a stimulant drug used to treat patients with attention deficit/hyperactivity disorder (ADHD), that is less likely to be abused during treatment.

The study, “PET Study Examining Pharmacokinetics, Detection and Likeability, and Dopamine Transporter Receptor Occupancy of Short- and Long-Acting Oral Methylphenidate,” conducted by Dr. Spencer, Assistant Director of Massachusetts General Hospital Pediatric Psychopharmacology Unit, investigates a new once-a-day capsule developed to release methylphenidate more slowly. Instead of dissolving in the gastrointestinal tract, it absorbs body fluids and uses osmotic pressure to slowly push the medication out of the capsule.

Methylphenidate increases attentiveness for patients with ADHD and lowers their hyperactivity. However, methylphenidate, like other stimulants, can also be abused by patients. Methylphenidate acts by blocking a protein called the dopamine transporter, which transports the neurochemical dopamine out of brain synapses. Blockade of the dopamine transporter by methylphenidate augments dopamine activity in the frontal cortex and improves the children’s ability to pay attention. Rapid increase of dopamine activity in other brain areas is perceived as pleasurable and can lead to patient abuse of methylphenidate.

Twelve healthy adults were randomly assigned to receive single doses of immediate-release methylphenidate or osmotic-release methylphenidate. Using positron emission tomography (PET), Spencer conducted a clinical comparison of conventional tablets and the new osmotic capsules. The new capsules succeeded in producing an adequate effect on neurotransmission, with fewer reports of pleasurable effects associated with abusable behavior.

PET scanning, the most sophisticated brain imaging technique for measuring dopamine transporter blockade, showed that the 90-mg capsule with sustained osmotic release produced the same blockade in the brains of healthy adults as 40 mg of immediate-release methylphenidate, but these effects occurred more slowly with the osmotic-release capsule.

“The study represents the first use of PET imaging to detect directly what is happening in the brain during the treatment of ADHD and to use that information to improve treatment,” said Robert Freedman, M.D., AJP editor-in-chief.

Study participants were asked about their subjective reactions to the two different capsules; those taking controlled-release methylphenidate reported significantly less detection of an effect and less liking of the effect. Detecting and liking a drug’s effects signal future abuse potential. Therefore, the controlled-release preparation offers the benefit of once-a-day dosing for patients with ADHD with less likelihood of future abuse.

The main features of ADHD include hyperactivity, impulsiveness, and an inability to sustain attention or concentration. These symptoms occur at levels that cause significant distress and impairment and are far more severe than typically found in children of similar ages and developmental levels. ADHD is a neurobiological disorder that can persist from childhood through adolescence and continue into adulthood.

The “PET Study Examining Pharmacokinetics, Detection and Likeability, and Dopamine Transporter Receptor Occupancy of Short- and Long-Acting Oral Methylphenidate,” study is supported by the National Institute of Mental Health and McNeil Consumer & Specialty Pharmaceuticals.

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Reference:
(Am J Psychiatry. 2006; 163: 387-395).

ADHD Often Improved After Tonsillectomy

In fact, about half of the children in the study who were found to have Attention-Deficit/Hyperactivity Disorder before tonsil surgery no longer met criteria for this diagnosis one year later. Other cognitive and behavioral issues also improved.

On the whole, the 78 children who had their tonsils out were much more likely than a comparison group of 27 children to have had behavior and sleep problems at the start of the study. But by the end of the study, tests showed little difference between the two groups.

The research paper is published online in the April issue of the journal Pediatrics by a team from the University of Michigan Health System. Data were collected from rigorous tests of sleep and breathing at night, and attention and behavior during the day. The results support previous observations of a link between children’s sleep-related breathing problems — such as snoring and breathing interruptions called apneas — and daytime behavior problems.

The researchers caution that their results do not yet prove cause and effect, and that tonsillectomy is not usually a “cure” for ADHD. But, they say, the growing body of evidence on this issue suggests that a significant number of children with inattention, hyperactivity, or sleepiness during the day – and also sleep-breathing problems at night – may benefit during both the night and day by tonsillectomy, an operation that was once performed on more than a million children a year but has become much less common in recent decades.

The procedure, also called adenotonsillectomy when both the tonsils and structures called adenoids are removed, is now performed on a few hundred thousand children a year. Nearly half of them have the surgery because enlarged tonsils and adenoids block the flow of air through their throat and impair their ability to breathe, and most of the rest because of repeated ear and throat infections. Almost all of the children who had surgery in the new study were thought by their surgeons to have symptoms of sleep apnea.

“These findings help support the idea that sleep-disordered breathing is actually helping to cause behavioral problems in children, and making them sleepy,” says lead author Ronald Chervin, M.D., M.S., director of the U-M Sleep Disorders Center and co-leader of the U-M Center for Sleep Science. “This is one of the first studies to document, using gold-standard measures, that all of these sleep and behavior problems tend to resolve one year after enlarged tonsils and adenoids are removed.”

One of the most striking findings – that children once diagnosed with ADHD no longer had the condition a year after tonsillectomy – occurred in 11 of 22 children with ADHD. This means that sleep and breathing problems are only part of the ADHD puzzle, and that tonsillectomy isn’t a cure-all for ADHD, notes Chervin, an associate professor of neurology at the U-M Medical School.

A few children even developed new ADHD a year after surgery. Chervin says this supports previous evidence that damage from sleep-disordered breathing may occur in early years, even though the result is not seen until later. If confirmed, this would mean that early diagnosis and treatment of sleep-disordered breathing are particularly important.

When they entered the study, and before any surgery, all the children in the study had their behavior assessed by a child psychiatrist, as well as by their parents, who completed standardized questionnaires. The children had their attention span and short-term memory measured using a standard computer-based test, and spent a night in the U-M Michael S. Aldrich Sleep Disorders Laboratory. There, they were monitored for breathing problems during sleep, and also for their level of sleepiness, as measured by how long it took them to fall asleep in a series of naps.

All the tests were repeated a year after the children had a tonsillectomy at U-M C.S. Mott Children’s Hospital or St. Joseph Mercy Health System, performed by otolaryngologists (ear, nose and throat doctors) from any of eight practices in the local area. For the comparison group, who had non-tonsil surgery or no surgery, the second round of testing was performed a year after initial tests. The researchers analyzed the test results using sophisticated statistical analysis.

Among those children scheduled for tonsillectomy, the sleep-breathing tests showed that before surgery, half of them had obstructive sleep apnea (OSA), usually in the mild to moderate range, in contrast to only one of the comparison children. At the end of the study, only 12 percent of the tonsillectomy patients had OSA, including one patient who hadn’t had it before tonsillectomy, compared with 3 children among the comparison patients who completed the sleep test series. In all, five children did not complete follow-up tests.

In people of any age, OSA occurs when breathing stops and starts repeatedly during the night, often in part because the throat is narrowed or blocked, keeping sufficient air from getting into the windpipe and lungs. People with sleep apnea often snore, or snort and gasp throughout the night, though not all snorers have sleep apnea. About one to three percent of children have OSA, including a good number of those children who snore regularly. Enlarged tonsils are a common cause of the sleep disorder in children, while obesity, allergies, acid reflux and structural abnormalities in the head and neck also contribute to it in children and adults.

Interruptions in breathing during sleep can cause the brain to “wake up” to some extent, even if the sleeping person is not aware of it. These repeated interruptions disturb the sleep patterns that are essential to a good night’s sleep – and are thought to be the reason why daytime behavior might be affected by poor breathing during the night. Sleep apnea is also linked to heart and blood pressure problems, and in children, to slow growth.

The researchers also compared the tonsillectomy patients who had had OSA before surgery with those who had not. In all, the children who had not had it before tonsillectomy were just as likely as the children with OSA to have a high score on standard tests of hyperactivity, and just as likely to have behavioral improvement after tonsillectomy.

As a result of this finding and other data, the study adds to an issue that’s currently puzzling sleep researchers: Why the results of sleep tests to monitor brain activity and breathing don’t always correlate with children’s daytime behavior. The standard measures used to assess children’s sleep problems, and the threshold levels that are used to assess the severity of a sleep problem, may need to be reevaluated, says Chervin.

To explore this issue further, he and his U-M colleagues are now recruiting patients for a study that will compare those standard measures with new ones, including a measure of how hard children work to breathe during the night, and another that looks for subtle changes in brain activity with every labored breathing cycle.

The bottom line for parents, Chervin and his colleagues say, is that any child who snores regularly, or has other signs of breathing problems during sleep, may benefit from an evaluation for sleep problems and perhaps from tonsillectomy – especially if the child is also having behavior problems at home or school.

“If you have a child who has difficulties with attention deficit, hyperactivity, or daytime sleepiness, there may be something that can be done about it if the child proves to have a sleep disorder,” Chervin says. “An undiagnosed sleep disorder is not the solution for all children with ADHD. But it could be something worth looking into for a substantial minority, especially those children with symptoms that suggest a sleep disorder such as sleep apnea.”

In addition to Chervin, the study’s authors are Deborah Ruzicka, R.N., Ph.D., of the Sleep Disorders Center; Bruno Giordani, Ph.D., Elise Hodges, Ph.D., and James Dillon, M.D., of the U-M Department of Psychiatry; Robert Weatherly, M.D., formerly of the U-M Department of Otolaryngology and now at the University of Kansas; Carole Marcus, MBBCh, of the Sleep Center at the Children’s Hospital of Philadelphia; and Kenneth Guire, M.S., of the U-M School of Public Health.

Study Suggests Strattera(R) Improved ADHD Symptoms In Patients With Comorbid Alcohol Abuse

Data from a recent clinical study showed Strattera(R) (atomoxetine HCl) improved symptoms of Attention- Deficit/Hyperactivity Disorder (ADHD) in patients with comorbid alcohol abuse disorder, suggesting ADHD can be treated safely and effectively with Strattera in patients with both disorders. Results from the 12-week study were presented today at a major medical meeting of psychiatrists.

The study was designed to test the hypothesis that Strattera is superior to placebo in the treatment of ADHD symptoms and prevention of relapse of alcohol abuse in adult patients with both ADHD and comorbid alcohol abuse disorder who were recently abstinent.

“ADHD is present in at least one-quarter of adults with alcohol abuse or dependence. Treating ADHD in adults with co-occurring alcohol abuse can be challenging, and up until now, no data have been available to help us know how to treat these patients. Often the first course of action is to treat the alcohol problem first, then later the ADHD,” said study author Timothy E. Wilens, M.D., director of substance abuse services in the Pediatric Psychopharmacology Clinics at Massachusetts General Hospital and associate professor of psychiatry at Harvard Medical School in Boston. “While additional studies are needed, this study is encouraging because it is the first to show that ADHD can be treated safely and effectively with Strattera in patients with ADHD and very recent alcohol abuse.”

Results of the study of 147 adults who met full DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders) criteria for ADHD and comorbid alcohol abuse, showed that Strattera was superior to placebo in the reduction of ADHD symptoms as measured by the ADHD Investigator Symptom Rating Scale (AISRS). At study endpoint of 12 weeks the reduction of ADHD symptoms in subjects with comorbid alcohol abuse disorder was significantly improved for the Strattera group (-13.63) relative to the placebo group (-8.31). The study showed no significant difference in time to alcohol abuse relapse between the Strattera and placebo treatment groups. However, an exploratory post hoc analysis undertaken to examine drinking throughout the study suggested a positive trend in reducing cumulative heavy drinking days by 26 percent in the treated group compared to placebo, though more study is needed to determine the validity of this specific finding.

ADHD is a potential risk factor for developing alcohol abuse problems.(1) In addition, alcohol abuse problems may be more common among people with ADHD than among those without ADHD. According to data from the National Comorbidity Survey Replication, nearly three times the number of individuals with ADHD (12 percent) have comorbid alcohol abuse or dependence disorder compared to the general population (4.4 percent).(2)

Strattera was generally well-tolerated in this study. Adverse events were similar to those noted in previous trials and discontinuations due to adverse events were not different between groups. The most common adverse events reported were nausea, dry mouth, decreased appetite, dizziness, fatigue, constipation and urinary hesitation. Discontinuation rates reported in this study from adverse events were 9.7 percent for the Strattera group compared to 2.7 percent for the placebo group.

Methods

In this randomized, placebo-controlled study, 72 patients received Strattera (25-100 mg daily) and 75 patients received placebo for approximately 12 weeks, at which time, their ADHD symptoms were measured using the AISRS. Study subjects were recently abstinent from alcohol at least four days before study randomization and included 125 men and 22 women, mean age approximately 34 years-old.

The study design allowed investigators to evaluate whether Strattera is superior to placebo in the treatment of ADHD symptoms and effective in preventing alcohol abuse relapse in adults with ADHD and comorbid alcohol abuse disorder. Time to relapse was defined as four standard alcoholic drinks for females or five standard alcoholic drinks for males within 24 hours, or at least three standard alcoholic drinks per day for at least one week. A standard alcoholic drink was defined in this study as 12 ounces of regular beer, 5 ounces of wine or 1.5 ounces of 80-proof distilled spirits. Cumulative heavy drinking days were measured post hoc with a stratified Andersen-Gill recurrent-event Cox model.

Does Stimulant Treatment For ADHD Increase Risk Of Drug Abuse?

Parents, doctors, and others have wondered whether common treatments for attention-deficit hyperactivity disorder (ADHD) inadvertently predispose adolescents to future drug abuse. The answer may depend on the age at which treatment is started and how long it lasts, say the authors of a new brain-imaging and behavioral study conducted in animals at the U.S. Department of Energy’s Brookhaven National Laboratory. The results appeared in the online issue of the journal Pharmacology, Biochemistry and Behavior.

“Our study shows that the brain’s reward pathways are definitely influenced by methylphenidate, one of the stimulant drugs commonly used to treat ADHD,” said Brookhaven researcher Panayotis (Peter) Thanos, lead author of the study. “But the brain chemistry changes we observed suggest that the developmental stage at which treatment begins and the duration of treatment are important variables that need further study.”

In the study, rats were given methylphenidate mixed with distilled water beginning one month after birth — early adolescence for rats. Animals received either 1 or 2 milligrams methylphenidate per kilogram of body weight, consistent with clinical doses given to children with ADHD. A control group of rats was handled under identical conditions but given plain water.

After two months of treatment, and again after eight months, the scientists performed positron emission tomography (PET) scans to measure the levels of dopamine D2 receptors, a type of brain receptor important for experiencing reward and pleasure that has been linked to pleasure and drug abuse. After the eight-month treatment, animals were also tested for their propensity to self-administer cocaine.

Rats given the 2mg/kg dose of methylphenidate were significantly less likely to press a lever to self-administer cocaine, and received fewer self-initiated infusions of the drug following eight months of treatment than the lower-dose group or the control rats.

The changes observed in brain chemistry were specific to the age and duration of methylphenidate treatment: Specifically, after two months of treatment, brain scans revealed that both groups of treated rats had lower levels of dopamine D2 receptors in their brains than did control animals.

In contrast, after eight months of treatment, the brain scans revealed elevated levels of dopamine D2 receptors in treated rats compared with controls, with the higher-dose treatment group showing the highest level of D2 receptors. In the control group, D2 receptor levels declined with age.

Research at Brookhaven and elsewhere has suggested that low levels of dopamine D2 receptors may increase the likelihood of drug abuse, while elevated levels of dopamine D2 receptors may attenuate the propensity to abuse drugs.

“This new study provides evidence that chronic methylphenidate treatment begun in adolescence affects the brain’s dopamine D2 receptor levels, and thus the brain’s reward circuitry, differently depending on the age and treatment duration,” Thanos said. The scientists’ observation of lower rates of cocaine self-administration in the animals treated for eight months with a 2kg/mg dose of methylphenidate supports this idea.

However, the observation of lower levels of D2 receptors after two months of treatment suggests that shorter lengths of treatment or the age at which treatment is evaluated could result in different effects. “Lower dopamine D2 receptor levels following short-term treatment could make the animals more vulnerable to drug self-administration during early adulthood,” Thanos said. “Unfortunately, we cannot compare cocaine self-administration following eight months of treatment with that obtained after two months of treatment in the same animals, since animals were not tested for cocaine self-administration at this earlier time,” Thanos said. “We wanted to avoid any confounding effect that might have resulted from cocaine exposure during this early developmental stage,” he explained.

Evaluating the effect of treatment duration is one avenue the researchers are exploring in follow-up studies “to help assess optimal duration of treatment regimes to minimize adverse effects on the propensity to abuse drugs,” Thanos said.

Thanos notes that the findings from this study cannot be directly extrapolated to treatment regimes used for ADHD. Also, these studies were done in healthy animals, not in rodent models of ADHD. All experiments were conducted in conformity with the National Academy of Sciences Guide for Care and Use of Laboratory Animals and Brookhaven National Laboratory Institutional Animal Care and Use Committee protocols.

ADHD In Adults Can Hurt Job Performance

Attention-deficit/hyperactivity disorder (ADHD) is a condition not limited only to childhood.

According to the April issue of Mayo Clinic Health Letter, more than half of children with ADHD can expect to contend with the condition as adults. ADHD in adults often is more subtle than in children, but still can be troublesome. It usually presents itself in one of two ways or a combination:

Inattention: Prioritizing and focusing on tasks can be enormous challenges. Organizing work or following instructions may be more difficult than it is for others.

Excessive levels of activity or difficult-to-control impulses: Adults with ADHD aren’t likely to be as physically active as hyperactive children with ADHD. Instead, adults may experience ongoing feelings of restlessness or have trouble relaxing. An adult may always feel the need to be on the go. Impulsivity may show up as impatience, mood swings, intense anger outbursts or trouble with relationships.

Tip-offs that a medical evaluation is needed include:

– A history of academic or career under achievement.

– Inconsistent work performance, such as frequently quitting or losing jobs.

– Difficulty managing daily responsibilities such as paying bills on time or completing household chores.

– Difficulty with relationships, perhaps related to such behaviors as forgetfulness, being easily angered or not completing tasks.

Interviews and detailed medical and behavioral histories are usually keys to diagnosis. Tests to measure attentiveness and concentration could be part of the evaluation.

Adult ADHD is generally managed with some combination of medication, psychotherapy or life coaching. Many adults with ADHD find counseling helpful. Counseling alone may be sufficient treatment for many adults with this illness.

Children With Both Autism And ADHD Often Bully

Children with both autism and attention deficit or attention deficit hyperactivity disorders are four times more likely to bully than children in the general population, according to a study released today in the journal, Ambulatory Pediatrics. However, the researchers caution against labeling these children simply as bullies.

“This is the first nationally representative study of bullying behaviors among children with autism. The majority of parents of children with autism and ADD or ADHD were concerned about their children’s bullying behaviors, but there is much we do not yet understand. It is too early to label these children as bullies.” said Guillermo Montes, Ph.D., senior researcher at Rochester, N.Y.-based Children’s Institute. “These children may have pent up energy that needs to be properly channeled, or they may have other underlying behavioral or medical issues that have not been addressed.”

The study pulled data from the 2003 National Survey of Children’s Health conducted by the National Center for Health Statistics. The sample included 53,219 children ages 6 to 17. The researchers were interested in finding out whether children with autism were more likely to bully other children. They hypothesized that that children with autism may bully more often because they are more often male (who are more likely to bully); they are more likely to be bullied (and victims are more likely to bully); and many children with autism require treatment for aggression (which potentially includes bullying).

But the researchers did not find that children with autism had a higher rate of bullying – unless they also had ADD or ADHD. Those with both disorders showed a rate four times higher than children with just autism and with children overall. They also had a higher rate of bullying than children with ADD or ADHD but no autism. This poses an important opportunity for health care providers who see children with autism and ADD or ADHD, which occurs in about half of children with autism spectrum disorders.

“It would be helpful for clinicians to be aware that so many parents of children with both autism and ADHD are describing bullying behaviors,” said Jill Halterman, M.D., M.P.H., associate professor of Pediatrics at the University of Rochester Medical Center and second author of the paper. “These children may benefit from additional support services, such as from a behavioral or mental health specialist, depending on the severity of symptoms. These services may be available through community based organizations or from the broader health care system.”

Effective Strategies For Decreasing Aggressiveness And Improving Behavior

Non-medicinal interventions are highly effective in preventing the behavioral and academic problems associated with Attention Deficit Hyperactivity Disorder (ADHD), according to a five-year study led by researchers at Lehigh University’s College of Education.

The study, titled “Project Achieve” and funded by the National Institute of Mental Health (NIMH), was the largest of its kind focusing on children aged 3 to 5 who have shown significant symptoms of ADHD. It also involved researchers from Lehigh Valley Hospital in Allentown, Pa.

The researchers, led by George DuPaul, professor of school psychology at Lehigh; Lee Kern, professor of special education at Lehigh; and Dr. John Van Brakle, chair of the pediatrics department at Lehigh Valley Hospital, studied 135 preschool students with ADHD symptoms. They evaluated the effectiveness of early intervention techniques in helping children decrease defiant behavior and aggression, while improving academic and social skills.

The study’s results are reported in a special series on ADHD in the most recent issue of School Psychology Review. Published by the National Association of School Psychologists, the quarterly is the world’s second-largest peer-reviewed psychology journal.

“Early identification and intervention are essential, but there has been a lack of research on how to identify and intervene effectively with these children during their preschool years,” said Thomas Power, editor of the journal and program director with the Center for Management of ADHD at The Children’s Hospital of Philadelphia.

“The investigation by Kern, DuPaul and their colleagues is the most ambitious study ever conducted of non-pharmacological, psychosocial interventions for young children with ADHD.”

The results were significant. Using a variety of early intervention strategies, parents reported, on average, a 17-percent decrease in aggression and a 21-percent improvement in their children’s social skills. Teachers saw similarly strong results; in the classroom, there was a 28-percent improvement in both categories. Early literacy skills improved up to three times over their baseline status.

“Medication may address the symptoms of ADHD,” says DuPaul, “but it does not necessarily improve children’s academic and social skills. And because this is a lifelong disorder, without any cure, it’s important that we start understanding what tools and strategies are effective for children with ADHD at such an early age.

“There’s simply a lack of understanding about the type of non-medicinal services that are available to preschool children and their families. Our goal is to address behavioral and academic issues before they become more problematic in elementary school.”

Early intervention techniques include highly individualized programs that often rely on positive supports to reinforce behavior. For example, in consultation with parents and preschool teachers, Project Achieve researchers modified the environments in home and school (such as altering tasks and activities in the classroom to accommodate for ADHD students) in an effort to improve behavior. The highly interactive techniques were presented as alternatives to medicine.

ADHD is a lifelong mental disorder that may become apparent in a child’s formative preschool years. The disorder, which makes it difficult for children to control their behavior and pay attention, affects about 7 percent of the school-aged population. The disorder has become a public health concern, however, because 40 percent of children who show signs of ADHD are suspended from preschool, while approximately 16 percent are eventually expelled.

The researchers suggest that a multi-tiered approach to intervention, offering more traditional services to at-risk children and more intensive services to children in greatest need, may be the most practical and cost-effective strategy for helping preschoolers overcome behavioral and academic challenges.

“While parents of children with ADHD usually trace the characteristic behaviors back to the preschool years,” says Van Brakle, “pediatricians have long questioned whether such children can accurately be identified, given the overlap with normal behaviors in young children. And if so, whether any intervention that does not involve medicine can be of value. Project Achieve suggests that with careful assessment, such children can be accurately identified and that appropriate behavioral interventions are an important part of the treatment plan.”

School Psychology Review’s special ADHD issue features two ADHD articles co-authored by researchers at Lehigh’s College of Education. DuPaul also contributed the Forward for the issue, which is titled, “School-Based Interventions for Students With Attention Deficit Hyperactivity Disorder: Current Status and Future Directions.”

As Cortex Normalizes In Teens With ADHD, Better Outcome Predicted By Gene

Brain areas that control attention were thinnest in children with attention deficit hyperactivity disorder (ADHD) who carried a particular version of a gene in a study by the National Institutes of Health’s (NIH) National Institute of Mental Health (NIMH). However, the areas, on the right side of the brain’s outer mantle, or cortex, normalized in thickness during the teen years in these children, coinciding with clinical improvement. Although this particular gene version increased risk for ADHD, it also predicted better clinical outcomes and higher IQ than two other common versions of the same gene in youth with ADHD.

“Since this gene version had similar structural effects in healthy children as in children with the disorder, our findings suggest that ADHD is at the far end of a continuum of normal traits,” said Philip Shaw, M.D., NIMH Child Psychiatry Branch, who led the research. “ADHD likely stems from interactions between several such genes and non-genetic factors.”

Shaw, Judith Rapoport M.D., and colleagues report on their magnetic resonance imaging (MRI) study in the August 2007 Archives of General Psychiatry.

“This study provides us with a first glimpse of how variation in a specific gene influences both brain development and clinical prognosis in ADHD,” said NIMH Director Thomas R. Insel, M.D.

When the NIMH researchers first reported last year that normalization of right cortex thickening was associated with better clinical outcomes in ADHD, there were few hints of a genetic connection. Yet evidence from several previous studies led them to suspect involvement of an ADHD-implicated version of a gene that codes for a receptor protein that binds to the brain chemical messenger dopamine.

This version of the dopamine D4 receptor gene, called the 7-repeat variant, accounts for about 30 percent of the genetic risk for ADHD, making it by far the strongest candidate gene implicated in the disorder. It’s called the 7-repeat because it contains the same repeating sequence in its genetic code seven times. Everyone inherits two copies of the D4 receptor gene, one from each parent, so some people have two copies of the same version while others may carry two different versions.

For the current study, the researchers scanned and determined the D4 gene types of 105 children with ADHD and 103 healthy controls and re-scanned them through their teen years.

They found that nearly one-fourth of youth with ADHD and in about one-sixth of the healthy controls had at least one copy of the 7-repeat version. Nearly two thirds of the ADHD youth and three-fourths of the healthy controls had the most common 4-repeat version; fewer than one-tenth in each group had a 2-repeat version.

While the 7-repeat version was linked to thinner attention-controlling cortex in both ADHD and healthy subjects, it appeared to confer advantage only among youth with ADHD. For example, participants with ADHD who lacked at least one copy of this 7-repeat variant had significantly lower IQs, and more than half of them still had pronounced ADHD symptoms when followed-up about six years later, compared to only 21 percent of those with at least one copy of the 7-repeat variant. There was also a trend toward better overall functioning among those with at least one copy of the 7-repeat variant at follow-up.

The MRI scans revealed that 7-repeat carriers with ADHD started out with the thinnest cortex areas important for controlling attention (right orbitofrontal and posterior parieto-occipital). The next thinnest were children with ADHD who did not have the 7-repeat version, followed by healthy children with the 7-repeat. Healthy children lacking the 7-repeat had the thickest cortex, but this did not appear to affect their IQ. However, the researchers note that other studies have found correlations between cortex thickness and certain measures of memory and intelligence.

In 7-repeat carriers with ADHD, the attention-controlling areas thickened to normal by age 16 (see time-lapse image below). Gene variants of two other dopamine system components showed few such anatomic correlates, confirming that the findings were specific to the D4 receptor gene.

“Some genes have a good side, even though they’re linked to disorder,” said Shaw, who noted that other traits linked to the 7-repeat version, such as novelty seeking and impulsiveness, might confer advantage in some settings. “Evidence suggests that the 7-repeat may be a relatively new variant that may have been favored through evolution because such traits proved adaptive for survival.”

The researchers are following up with studies on the relationship between cortex thickness and cognitive features of ADHD, such as working memory and the ability to inhibit responses.