From ScienceDaily.com

In youth with attention deficit hyperactivity disorder (ADHD), the brain matures in a normal pattern but is delayed three years in some regions, on average, compared to youth without the disorder, an imaging study by researchers at the National Institutes of Health’s (NIH) National Institute of Mental Health (NIMH) has revealed. The delay in ADHD was most prominent in regions at the front of the brain’s outer mantle (cortex), important for the ability to control thinking, attention and planning. Otherwise, both groups showed a similar back-to-front wave of brain maturation with different areas peaking in thickness at different times.

“Finding a normal pattern of cortex maturation, albeit delayed, in children with ADHD should be reassuring to families and could help to explain why many youth eventually seem to grow out of the disorder,” explained Philip Shaw, M.D., NIMH Child Psychiatry Branch, who led research team.

Previous brain imaging studies failed to detect the developmental lag because they focused on the size of the relatively large lobes of the brain. The sharp differences emerged only after a new image analysis technique allowed the researchers to pinpoint the thickening and thinning of thousands of cortex sites in hundreds of children and teens, with and without the disorder.

“If you’re just looking at the lobes, you have only four measures instead of 40,000,” explained Shaw. “You don’t pick up the focal, regional changes where this delay is most marked.”

Among 223 youth with ADHD, half of 40,000 cortex sites attained peak thickness at an average age of 10.5, compared to age 7.5 in a matched group of youth without the disorder.

Shaw, Judith Rapoport, M.D., of the NIMH Child Psychiatry Branch, Alan Evans, M.D., of McGill University, and colleagues report on their magnetic resonance imaging (MRI) study during the week of November 12, 2007, in the online edition of the Proceedings of the National Academy of Sciences.

The researchers scanned most of the 446 participants — ranging from preschoolers to young adults — at least twice at about three-year intervals. They focused on the age when cortex thickening during childhood gives way to thinning following puberty, as unused neural connections are pruned for optimal efficiency during the teen years.

In both ADHD and control groups, sensory processing and motor control areas at the back and top of the brain peaked in thickness earlier in childhood, while the frontal cortex areas responsible for higher-order executive control functions peaked later, during the teen years. These frontal areas support the ability to suppress inappropriate actions and thoughts, focus attention, remember things from moment to moment, work for reward, and control movement — functions often disturbed in people with ADHD.

Circuitry in the frontal and temporal (at the side of the brain) areas that integrate information from the sensory areas with the higher-order functions showed the greatest maturational delay in youth with ADHD. For example, one of the last areas to mature, the middle of the prefrontal cortex, lagged five years in those with the disorder.

The motor cortex emerged as the only area that matured faster than normal in the youth with ADHD, in contrast to the late-maturing frontal cortex areas that direct it. This mismatch might account for the restlessness and fidgety symptoms common among those with the disorder, the researchers suggested.

They also noted that the delayed pattern of maturation observed in ADHD is the opposite of that seen in other developmental brain disorders like autism, in which the volume of brain structures peak at a much earlier-than-normal age.

The findings support the theory that ADHD results from a delay in cortex maturation. In future studies, the researchers hope to find genetic underpinnings of the delay and ways of boosting processes of recovery from the disorder.

“Brain imaging is still not ready for use as a diagnostic tool in ADHD,” noted Shaw. “Although the delay in cortex development was marked, it could only be detected when a very large number of children with the disorder were included. It is not yet possible to detect such delay from the brain scans of just one individual. The diagnosis of ADHD remains clinical, based on taking a history from the child, the family and teachers.”

Also participating in the research were: Kristen Eskstrand, Wendy Sharp, Jonathan Blumenthal, Dede Greenstein, Liv Clasen, and Jay Giedd, M.D., NIMH.

The National Institute of Mental Health (NIMH) mission is to reduce the burden of mental and behavioral disorders through research on mind, brain, and behavior.

From Nature News

Does breast-feeding a child boost its brain development and raise its intelligence? Only if the child carries a version of a gene that can harness the goodness of breast-milk, say researchers.

The results add to the nature versus nurture debate over intelligence, by showing how the two effects can interact.

The question of whether people are born intelligent or made intelligent by their environment has been debated for decades. Research with identical twins separated at birth has shown that both genetics and rearing conditions are important in determining intelligence.

One of the important environmental effects seems to be breast-feeding. Children who are breast-fed generally perform better in IQ tests than do those fed on other types of milk. Researchers think that this might be because specific fatty acids found in human milk, but not in cows milk or infant formulas, improve brain development.

Avshalom Caspi and Terrie Moffitt, psychologists at Kings College, London, and their colleagues looked at the relationship between breast-feeding and intelligence to explore the possibility that in this case nature and nurture might be intimately linked.

The group first looked for genes that metabolize fatty acids, which in turn are important for the growth of neurons. Differences in such genes, they hypothesized, might moderate the intellectual advantage associated with breast-feeding. They searched the literature and gene databases and found a good candidate: a gene called FADS2 .

Class test

The team then looked at more than 1,000 children in New Zealand who were born in 1972 and IQ tested at ages 7, 9, 11, and 13; a record was kept of which children had been breast-fed. The study was repeated with about 2,200 children in Britain who were born in 199495 and IQ tested at age 5. DNA tests were used to look at a specific spot in their FADS2 genes, to see which version or allele of the gene they carried.

In children who carried at least one copy of a C allele for FASD2 , those who were breast-fed generally had a higher IQ than those who were not: by an average of 6.4 IQ points in the New Zealand study, and by 7.0 IQ points in the British one. By contrast, children carrying two G alleles had roughly the same IQ irrespective of their diet. About 10% of the population is thought to be GG.

We had a very strong hypothesis, but it could easily have turned out wrong, so we were pleased when the data fit the hypothesis in New Zealand, and then really delighted when it was confirmed in Britain, says Moffitt. The team reports their findings in the Proceedings of the National Academy of Sciences 1.

Why and how this genetic difference came into being is unclear. It is almost as though the G allele evolved as a protective genotype for children who might not get enough breast-milk, says developmental psychologist Linda Gottfredson at the University of Delaware in Newark.

Mother care

The result will help to settle the debate over whether breast-feeding is linked to intelligence because of the nutritional quality of the milk, or because mothers who breast-feed are the sorts of mothers who encourage child learning. I think this research will settle that debate, or at the very least bring it near a close, says epidemiologist Jean Golding at the University of Bristol, UK.

Many of us are starting to think that nature via nurture might be a better catch phraseAvshalom Caspi

From ScienceDaily.com

Three decades ago, medical investigators began sounding the alarm about how lead exposure causes IQ deficits in children. Today, researchers at the University of Virginia Health System say children with sleep disorders can face similar risks of intellectual impairment.

UVa researchers have been studying sleep disturbances in children with enlarged tonsils and adenoids for the past seven years. In a recent study, they discovered that youngsters who snore nightly scored significantly lower on vocabulary tests than those who snore less often.

“Vocabulary scores are known to be the best single predictor of a child’s IQ and the strongest predictor of academic success,” explains Dr. Paul M. Suratt, a pulmonologist who directs the UVa Sleep Laboratory.

According to Dr. Suratt, the vocabulary differences associated with nightly snoring are equivalent to the IQ dissimilarities attributed to lead exposure. “Studies show that, even at nontoxic levels, lead exposure can reduce a child’s IQ by more than seven points,” he notes.

Sleep disorders can be intellectually and behaviorally detrimental to children because they interrupt the deep sleep patterns needed for healthy development. At night, children with sleep disorders can be observed snoring, snorting, gasping, tossing and turning. During the day, these children can be irritable, hyperactive and unable to concentrate.

A key goal of the UVa researchers is to predict which children with sleep disorders are most likely to suffer cognitive impairment or develop behavior problems. “It’s more difficult than you would think,” Dr. Suratt explains. “Children with sleep disordered breathing may have cognitive impairment even if they don’t completely stop breathing, even if their oxygen levels don’t fall and even if they don’t totally wake up.”

In a series of studies involving six to twelve-year-olds, researchers have been piecing together a list of risk indicators. So far, snoring frequency combined with sleep lab results have proven to be the most reliable predictors of intellectual impairment and behavioral problems. Sleep duration and race appear to be important risk factors, too.

“One of our most recent studies found that kids who snore nightly and spend less time in bed score significantly lower on cognitive tests than children who snore less frequently and spend longer times bed,” Dr. Suratt explains. “We’ve also found that obstructive sleep disordered breathing (OSBD) occurs more often in African American children and, therefore, places them at greater risk of cognitive impairment.”

As part of their quest to accurately identify at-risk children, UVa researchers are now testing a device that records breathing sounds during sleep at home. When used in the lab, this method has proven more sensitive than existing equipment in detecting sleep apnea in children.

“We’re getting closer to the day when we can quickly establish risk profiles and effective treatment plans for children with sleep disorders. Our goal is to minimize the cognitive and behavioral problems that often develop,” says Dr. Suratt

From ScienceDaily

Daily television viewing for two or more hours in early childhood has been linked to behavioral problems and poor social skills, a U.S. study found.

A study of children ages 2.5 to 5.5 years, conducted by researchers at the Johns Hopkins Bloomberg School of Public Health in Baltimore, found that the impact of TV viewing on a child’s behavior and social skills varied by the age at which the viewing occurred, but heavy television viewing that decreased over time was not associated with behavior or social problems.

Lead author Kamila Mistry, a doctoral candidate at The Johns Hopkins Bloomberg School, analyzed data for 2,707 children collected from the Healthy Steps for Young Children national evaluation. Parents were surveyed about their child’s television viewing habits and behavior at 2.5 and at 5.5 years of age.

The study, published in the journal Pediatrics, found that having a television in the child’s bedroom at 5.5 years of age was associated with behavioral problems, poor social skills and poor sleep. Forty-one percent of the children in the study had a television in their bedroom.

Dr. Perlmutter’s comment:

Nice to see validation of our earlier publication in Raise a Smarter Child by Kindergarten

From Washington University

A team of researchers from the University of Virginia Health System and Washington University School of Medicine in St. Louis has found that drugs commonly used to anesthetize children can cause brain damage and long-term learning and memory disturbances in infant rats. The researchers report their findings in the Feb. 1 issue of the Journal of Neuroscience.

We frequently perform surgical procedures on children, including premature infants, and those procedures have become increasingly more complex and take longer to perform, says the studys lead author Vesna Jevtovic-Todorovic, M.D., associate professor of anesthesiology at the University of Virginia Health System. That means many pediatric patients are being exposed to anesthetic drugs more frequently and for longer periods of time. Our results would suggest that might be problematic.

Previously, Jevtovic-Todorovic was at Washington University School of Medicine in St. Louis, where the rest of the research team is located. The investigators anesthetized 7-day-old rats with a combination of three drugs

midazolam, nitrous oxide and isoflurane

commonly used in pediatric surgery.

As the animals recovered from the anesthesia, the researchers divided them into three groups: One group was sacrificed the next day and their brains examined, a second group grew to be about a month old and a third group grew into adulthood. The latter two groups were tested for effects of anesthesia on learning and memory. Members of the research team also recorded electrical activity in the hippocampus, a brain structure known to be important in learning and memory.

These infant rats were anesthetized during the brain growth spurt period called synaptogenesis, which lasts for the first few weeks of life in rats, but in humans it extends from the third trimester of pregnancy until about age 3, says senior investigator John W. Olney, M.D., the John P. Feighner Professor of Neuropsychopharmacology at Washington University School of Medicine in St. Louis. During this period, nerve cells in the brain make connections with one another and form large networks. But if something interferes with that process, the cells are programmed to kill themselves.

In this study, the team found moderately severe cell death had occurred in several brain regions in every brain examined. This included brain regions involved in learning and memory such as hippocampus.

In addition, the rats exposed to anesthesia in infancy had significant learning and memory deficits, both at 1 month of age and in adulthood. Rats were tested in several kinds of mazes that behavioral scientists commonly use to evaluate learning and memory. In all of these tests, rats that had been anesthetized in infancy were significantly worse than those that had not been given the standard anesthesia drug combination.

The researchers also examined brain slices from the hippocampus of month-old rats. They ran electrical currents through those slices to induce a process known as long-term potentiation (LTP), which is thought to occur during learning and memory formation. Brain slices from rats who had been anesthetized with the three drug cocktail had far less LTP activity than normal.

In each part of this study, we found essentially what we expected, Jevtovic-Todorovic says. Once we had confirmed cell death, we would have expected behavioral deficits, and we found those as the rats grew into adulthood. In the electrophysiological experiments, we also found evidence of disturbances in the neural circuits of the hippocampus, the brain region which, through those circuits, plays an important role in learning and memory.

The team also found that the rats appeared to behave normally in most other ways, and there were no outward signs of brain damage.

Thats important because if similar brain damage had occurred in a human infant, it appears there would not be any overt signs that would alert you to it, Olney says.

This study fits together with a line of research that has repeatedly identified a relationship between certain classes of drugs that inhibit nerve cell activity and damage to the developing brain. Anesthetic drugs work in one of two ways, both of which inhibit nerve cell activity: Either they inhibit excitatory neurotransmission in the brain or they enhance inhibitory neurotransmission.

The excitatory system that stimulates nerve cells is what scientists call the NMDA glutamate transmitter system. In 1998, Jevtovic-Todorovic discovered that the drug nitrous oxide, or laughing gas, work by inhibiting the NMDA glutamate system. Another anesthetic drug known as Ketamine, also works by inhibiting the NMDA glutamate system.

Other anesthetic drugs work by enhancing the inhibitory activity of GABA (Gamma Amino Butyric Acid). GABA is the primary inhibitory transmitter in the brain.

In related research, Olney and colleagues in Germany demonstrated that when the developing brain is exposed to drugs that block NMDA glutamate activity, nerve cells in the brain commit suicide. They also found that drugs that enhance GABA activity can cause nerve cells in the developing brain to self-destruct.

The above findings prompted them to study alcohol, which is known to block NMDA glutamate activity and also to enhance GABA activity. They found that alcohol powerfully triggers nerve cell suicide in the developing brain, providing a likely explanation for the learning and memory disturbances associated with the human fetal alcohol syndrome. More recently, Olney and colleagues demonstrated that sodium channel blocking drugs used in pediatric medicine to manage epilepsy also cause nerve cell suicide in the infant rat brain.

In all of these studies, we have found that drugs that enhance GABA inhibition or that inhibit glutamate excitation can trigger massive cell suicide in the developing brain, Olney says. If you put nerve cells to sleep when they are supposed to be making connections, it interferes with their timing, and nerve cells are programmed to kill themselves if they dont make their connections on time.

Part of the reason cells are programmed to self-destruct is that there is redundancy built into the system. An infant is born with an excess number of nerve cells, and some cell death is normal in the developing brain. But Olneys team has found that when drugs interfere with the cell and put it to sleep when it is trying to make connections, the suicide rate rises to abnormally high proportions.

Previous studies by these researchers have helped explain how abuse of certain drugs, including alcohol, can damage the developing brain. But in the present study by Jevtovic-Todorovic and colleagues, the investigators found that drugs used commonly in pediatric anesthesia also can damage the developing brain.

According to Olney, this is a serious dilemma because anesthesia is required to do surgery, and surgery is the only option for some infants with life-threatening problems.

But some pediatric surgery is elective, Olney says. In light of these findings, I would recommend that if surgery really does not have to be performed early in life, it would be prudent to postpone it.

The investigators also suggest that some surgical procedures might not require general anesthesia, or in some cases the duration of general anesthesia could be reduced. They also say that the common practice of keeping newborns continuously sedated in pediatric intensive care units should carefully be evaluated in order to minimize potential damage from the sedating drugs.