Disorders that Appear in Childhood

by Dana Alliance for Brain Initiatives

January, 2006

Brain disorders that appear in childhood often spark controversy, with heated public debate about proper diagnosis and treatment. In 2005 researchers continued the effort to better understand the neurological basis of three such disorders: attention-deficit hyperactivity disorder, dyslexia, and autism.

Challenging Assumptions about ADHD

Attention-deficit hyperactivity disorder (ADHD) is the most commonly diagnosed psychiatric disorder in children, affecting an estimated 8 to 10 percent of schoolchildren,1 yet it is also one of the most controversial. Some people doubt that ADHD is a real disorder, chalking up any inattentiveness and hyperactivity in children to a lack of discipline or maturity. Others believe that the disorder is real but worry that children are being overmedicated. Research reported in 2005 helped clarify some issues, but in other cases raised new ones.

Two studies published in 2005 challenge the accepted wisdom about differences between boys and girls in ADHD. Although it is known that ADHD affects more boys than girls, the estimated prevalence rates vary depending on whether researchers are studying children being treated in clinics or analyzing a more general sampling of children who live in the community. One meta-analysis (a study that involves reviewing data from multiple separate but similar experiments), published in the Journal of the American Academy of Child and Adolescent Psychiatry, found that in clinics, the number of boys being treated is six to nine times greater than the number of girls, while in the community, only three times as many boys have the disorder.2

What accounts for the discrepancy? Until now, the prevailing view was that ADHD must manifest itself differently in boys and girls, causing different symptoms. In particular, boys with ADHD were believed to be more hyperactive and disruptive than girls, leading to problems in the classroom that prompted parents and teachers to seek referrals for treatment.

But a study published in 2005 by Joseph Biederman and colleagues at Massachusetts General Hospital challenged the belief that ADHD differs significantly in boys and girls. As reported in the June issue of the American Journal of Psychiatry, 3 Biederman and his team studied a sample of children in the community. Using standard diagnostic techniques, they diagnosed ADHD in a subset of children living in the community who had never been referred for treatment of ADHD.

Consistent with previous community studies, ADHD was about three times as prevalent in boys as in girls. But when Biederman and his colleagues delved deeper, they found no significant differences between the boys and girls in age of ADHD onset, symptoms, impairment, subtype (inattentive, hyperactive-impulsive, or combined), or the presence of other disorders along with ADHD.

Why are so many more boys than girls being referred for treatment? Although the reasons are not clear, the cause could be referral bias, says Biederman. In his experience, boys with ADHD tend to be more outwardly disruptive than girls, especially when they are young, and this slight gender variation in the way disruptive behavior is expressed probably is what leads to referrals. Yet this also means girls with ADHD may not be diagnosed and treated as often as they should. If the study is replicated in other community populations, it could have important implications for the detection and management of ADHD in girls.

Further support for the view that boy vs. girl differences in ADHD may be overrated is provided by a large study in twins and their siblings born singly, led by Florence Levy at the University of New South Wales in Australia.4 As reported in the April issue of the Journal of the American Academy of Child and Adolescent Psychiatry, the researchers found few differences between boys and girls in the occurrence of disorders frequently diagnosed along with ADHD, such as conduct disorder, oppositional defiant disorder (characterized by persistent uncooperativeness and hostility), and separation anxiety disorder. The one exception was that girls with ADHD were slightly more likely to be diagnosed with anxiety disorder. Otherwise, ADHD subtype and severity of ADHD symptoms, rather than gender, determined whether other disorders were present, and, if so, how severe they were.

ADHD subtype and severity of ADHD symptoms, rather than gender, determined whether other disorders were present, and, if so, how severe they were.

Other studies published in 2005 investigated the neurological basis of impulsivity and deficits in what are called “executive functions”—planning, organizing, and decision-making. These problems can affect school and work performance in ways that can limit an individual’s intellectual growth and professional achievement. Katya Rubia and colleagues at King’s College London used functional magnetic resonance imaging to identify patterns of brain activation in 16-year-old boys with ADHD who had never been treated with medication. As reported in the June issue of the American Journal of Psychiatry, 5 the researchers conducted brain scans while asking the boys to perform a task that measured inhibition control (a way to gauge impulsivity).

Researchers at King’s College London found that boys with attention deficit hyperactivity disorder show less activity in the right inferior prefrontal cortex when they perform a task successfully, as indicated by these scans. Reprinted with permission from the American Journal of Psychiatry, (© 2005). American Psychiatric Association.

When compared with the control group without ADHD, boys with the disorder showed reduced activation in the right inferior prefrontal cortex when they successfully performed the task, and reduced activation in the posterior cingulate and precuneus when they did not complete the task successfully. This pattern of brain activation not only differed from that seen in the control group, but also was nearly identical to the findings in a group of boys with ADHD who were medicated. This suggests that the problem is inherent to ADHD and not caused by medication.

Although questions remain about the brain basis of ADHD, the consensus about treatment remains the same. In June 2005, the American Academy of Pediatrics issued a detailed review of the evidence behind its current treatment guidelines to help pediatricians see how different treatment options compare and choose one over the others.6 As reported in the academy’s journal, Pediatrics, the medications studied in most detail were the stimulants methylphenidate (Ritalin), dextroamphetamine (Dexedrine), and pemoline, with some mention made of the tricyclic antidepressant desipramine (Norpramin) and the non-stimulant atomoxetine (Strattera).

Although questions remain about the brain basis of ADHD, the consensus about treatment remains the same.

The report strongly endorses treatment with stimulant drugs to treat core symptoms and concludes that all stimulant drugs are equally effective. Tricyclics and atomoxetine, which are antidepressant medications, provide options for children who do not respond to stimulants. (It should be noted, however, that the FDA required late in 2005 that a black box warning be added to atomoxetine because it may increase suicidal thoughts in some children.) The authors endorse what has become the consensus opinion about treatment, however: the best approach probably involves a combination of medication and behavioral therapy.

Investigating the Brain Basis of Dyslexia

Children with dyslexia usually have normal intelligence, but they have difficulty learning how to read. Exactly what brain abnormalities are responsible remains a matter of debate. Two studies published in 2005 may help provide answers.

Children with dyslexia also frequently are unable to correctly name objects such as those they see in pictures. Wondering if the same neurological abnormality might underlie both defects, researchers led by Eamon J. McCrory of the Institute of Psychiatry in London used positron emission tomography scans to map patterns of brain activation in children with dyslexia.

As reported in the February issue of Brain, they found that children with dyslexia showed reduced activation in the left inferior occipitotemporal cortex while trying to read words or name pictures—suggesting that the underlying problem is a deficit in the processing of sounds.7 The research, if confirmed, has practical implications: identifying preschool-age children who have trouble naming pictures, and then providing remedial help from a speech and language specialist, might help improve later reading ability.

Another study reported in 2005 provided a surprising new twist to the theory that dyslexia involves a problem in actually seeing words. Researchers led by Anne J. Sperling at the Georgetown University Medical Center reported in the July issue of Nature Neuroscience that the real problem may be an inability to discriminate visual cues from background signals called “noise.”8

The researchers asked children to look at a series of patterns, both flickering and static, on a computer screen and to say whether the patterns appeared on the left or right side. When the patterns alone appeared on the screen, children with dyslexia could identify them as often as other children. But when the researchers partly obscured the patterns by adding visual “noise” in the form of television-like “snow,” the children with dyslexia were less able than their peers to identify the patterns. The authors propose that the underlying problem in dyslexia may therefore involve an inability to screen out background “noise” and focus on important signals.

Seeking Early Signs of Autism

In 2005 scientists continued to provide evidence that the brain abnormalities that cause autism can be detected in the first months and years of life, even though this developmental disorder is usually not diagnosed until the child’s second or third year.

Already at a first birthday party, children with early-onset autism show symptoms of the disorder, as was the case with the baby on the right. Babies with later-onset autism and babies developing normally, such as the one on the left, also were studied. Screen captures courtesy of Dr. Geraldine Dawson

In the April/May 2005 issue of the International Journal of Neuroscience, Lonnie Zwaigenbaum and colleagues at McMaster University in Ontario report that some signs of autism are evident in babies as young as 6 months.9 Their pilot study involved 65 infant siblings of children with autism, recruited around age 6 months and followed until age 2 or older. (This pilot study has since mushroomed into what is now known as the High Risk Baby Autism Research Project, under way at 14 sites in Canada and the United States.)

The researchers tested the babies at 6 and 12 months to measure behaviors and emotional reactions that sometimes become abnormal in autism. They identified characteristics, noticeable in children by their first birthday, that may predict a diagnosis of autism later. These include reduced capacity to shift visual attention when there were competing stimuli, other abnormalities in visual behaviors such as orienting to name, and exaggerated reactions to stress.

Even at 6 months, babies later diagnosed with autism exhibited certain telltale behaviors. For example, babies who were passive and inactive at 6 months and who at 12 months became extremely irritable and tended to fixate on particular objects were more likely to be diagnosed with autism. The authors emphasize, however, that the results are based on a relatively small sampling and are preliminary. Nor have any of the observed behaviors been correlated with measures of early brain development; trying to do so by methods such as brain scans poses technical and ethical challenges in infants. Even so, the study, if replicated, may provide a way to identify earlier in life some children with autism.

Another study published in 2005 involved an analysis of home movies of children’s birthday parties that builds on a 1994 study now considered classic because it provided what is believed to be the first objective evidence that autistic regression exists. As reported in the August issue of the Archives of General Psychiatry, Geraldine Dawson at the University of Washington (who also authored the classic 1994 study) and her colleague Emily Werner viewed home birthday videos taken at the first and second birthdays of 56 children, 21 with early-onset autism, 15 with later-onset autism, and 20 who were developing normally.10

They found that the children with early-onset autism displayed symptoms of the disorder at the first birthday party, while those with later-onset autism displayed behaviors that were indistinguishable from the behaviors of the healthy babies. By the second birthday party, however, those babies who initially appeared healthy and were later diagnosed with autism had clearly regressed, supporting parents’ anecdotal reports. Research is now under way to better understand the cause and long-term prognosis of autistic regression.