Posts tagged FASD
Articles and news from the latest research reports.
Prenatal Alcohol Exposure Alters Development of Brain Function
In the first study of its kind, Prapti Gautam, PhD, and colleagues from The Saban Research Institute of Children’s Hospital Los Angeles found that children with fetal alcohol spectrum disorders (FASD) showed weaker brain activation during specific cognitive tasks than their unaffected counterparts. These novel findings suggest a possible neural mechanism for the persistent attention problems seen in individuals with FASD. The results of this study will be published in Cerebral Cortex on August 4.
“Functional magnetic resonance imaging (fMRI) has been used to observe brain activity during mental tasks in children with FASD, but we are the first to utilize these techniques to look at brain activation over time,” says Gautam. “We wanted to see if the differences in brain activation between children with FASD and their healthy peers were static, or if they changed as children got older.”
FASD encompasses the broad spectrum of symptoms that are linked to in utero alcohol exposure, including cognitive impairment, deficits in intelligence and attention and central nervous system abnormalities. These symptoms can lead to attention problems and higher societal and economic burdens common in individuals with FASD.
During the period of childhood and adolescence, brain function, working memory and attention performance all rapidly improve, suggesting that this is a crucial time for developing brain networks. To study how prenatal alcohol exposure may alter this development, researchers observed a group of unaffected children and a group of children with FASD over two years. They used fMRI to observe brain activation through mental tasks such as visuo-spatial attention—how we visually perceive the spatial relationships among objects in our environment —and working memory.
“We found that there were significant differences in development brain activation over time between the two groups, even though they did not differ in task performance,” notes Elizabeth Sowell, PhD, director of the Developmental Cognitive Neuroimaging Laboratory at The Saban Research Institute and senior author on the manuscript. “While the healthy control group showed an increase in signal intensity over time, the children with FASD showed a decrease in brain activation during visuo-spatial attention, especially in the frontal, temporal and parietal brain regions.”
These results demonstrate that prenatal alcohol exposure can change how brain signaling develops during childhood and adolescence, long after the damaging effects of alcohol exposure in utero. The atypical development of brain activation observed in children with FASD could explain the persistent problems in cognitive and behavioral function seen in this population as they mature.
Paying closer attention to attention
Ellen’s (not her real name) adoptive parents weren’t surprised when the school counselor suggested that she might have attention deficit hyperactivity disorder (ADHD).
Several professionals had made this suggestion over the years. Given that homework led to one explosion after another, and that at school Ellen, who is eleven, spent her days jiggling up and down in her seat, unable to concentrate for more than ten minutes, it seemed a reasonable assumption. Yet her parents always felt that ADHD didn’t quite capture the extent of Ellen’s issues over the years. Fortunately the school counsellor was familiar with fetal alcohol spectrum disorder (FASD). When she learned that Ellen’s birth mother had consumed alcohol during pregnancy, she raised the possibility that Ellen’s problems could be attributable to FASD and referred her for further assessment.
It’s a familiar story, and most of us reading about Ellen would assume that she did indeed suffer from ADHD.
But now researchers from McGill have suggested that there may be an overreporting of attention problems in children with FASD, simply because parents and teachers are using a misplaced basis for comparison. They are testing and comparing children with FASD with children of the same physical or chronological age, rather than with children of the same mental age, which is often quite a lot younger.
“Because the link between fetal alcohol syndrome and ADHD is so commonly described in the literature, both parents and teachers are more likely to expect these children to have attention problems,” says Prof. Jacob Burack, a professor in McGill’s Dept. of Educational and Counselling Psychology and the senior author on a recent study on the subject. “But what teachers often don’t recognize is that although the child they are dealing with is eleven years old in chronological terms, they are actually functioning at the developmental age of an eight-year old. That’s a pretty big difference. And when you use mental age as the basis of comparison, many of the attention problems that have been described in children with FASD no longer seem of primary importance.”
The researchers recruited children with FASD whose average chronological age was just under twelve years old. But their average mental age, determined by standard tests, was actually closer to nine-and-a-half years old. (The children were recruited through the Asante Centre for Fetal Alcohol Syndrome in British Columbia, and though the number of children studied may appear small, this is a fairly typical size for studies on FASD, given the difficulties of the diagnostic process.)
These children were then compared with children who were developing typically and whose average chronological age was about eight-and-a-half years old and whose average mental age was similar to that of the group of children diagnosed with FASD.
After using tests to measure specific aspects of attention, the researchers then compared the performance of children with FASD on these tests with the results of children of the same mental age. What they found was that while children like Ellen had difficulties with certain kinds of attention skills, notably in terms of shifting attention from one object to another, there were other areas, such as focus, where they had no significant difficulties at all. So, if we were to compare these aspects of attention to a hockey game, typically these children would have no difficulty focusing on the puck in the arena, but would have problems following the puck being passed from one player to another.
This suggests to Dr. Kimberly Lane, the PhD student who conducted the research, that there is a need to develop a more nuanced understanding of attention skills. “We use words like attention loosely, but it’s really an umbrella term that covers various aspects of attending to different people or events or environments,” says Dr. Lane. “By using more complex assessment techniques of various aspects of attention it will be possible to get a better picture of the attention difficulties faced by children with FASD,” she adds.
“But no matter what the tests say, it’s important for teachers and parents to understand that.the difficulties these children have with attention may be less important than their more general problems, and we need to work with them as they are.”
(Source: mcgill.ca)
Prenatal Exposure to Alcohol Disrupts Brain Circuitry
Prenatal exposure to alcohol severely disrupts major features of brain development that potentially lead to increased anxiety and poor motor function, conditions typical in humans with Fetal Alcohol Spectrum Disorders (FASD), according to neuroscientists at the University of California, Riverside.
In a groundbreaking study, the UC Riverside team discovered that prenatal exposure to alcohol significantly altered the expression of genes and the development of a network of connections in the neocortex — the part of the brain responsible for high-level thought and cognition, vision, hearing, touch, balance, motor skills, language, and emotion — in a mouse model of FASD. Prenatal exposure caused wrong areas of the brain to be connected with each other, the researchers found.
These findings contradict the recently popular belief that consuming alcohol during pregnancy does no harm.
“If you consume alcohol when you are pregnant you can disrupt the development of your baby’s brain,” said Kelly Huffman, assistant professor of psychology at UC Riverside and lead author of the study that appears in the Nov. 27 issue of The Journal of Neuroscience, the official, peer-reviewed publication of the Society of Neuroscience. Study co-authors are UCR Ph.D. students Hani El Shawa and Charles Abbott.
“This research helps us understand how substances like alcohol impact brain development and change behavior,” Huffman explained. “It also shows how prenatal alcohol exposure generates dramatic change in the brain that leads to changes in behavior. Although this study uses a moderate- to high-dose model, others have shown that even small doses alter development of key receptors in the brain.”
Researchers have long known that ethanol exposure from a mother’s consumption of alcohol impacts brain and cognitive development in the child, but had not previously demonstrated a connection between that exposure and disruption of neural networks that potentially leads to changes in behavior.
Huffman’s team found dramatic changes in intraneocortical connections between the frontal, somatosensory and visual cortex in mice born to mothers who consumed ethanol during pregnancy. The changes were especially severe in the frontal cortex, which regulates motor skill learning, decision-making, planning, judgment, attention, risk-taking, executive function and sociality.
The neocortex region of the mammalian brain is similar in mice and humans, although human processing is more complex. In previous research, Huffman and her team created what amounts to an atlas of the neocortex, identifying the development of regions, gene expression and the cortical circuit over time. That research is foundational to understanding behavioral disorders such as autism and FASD.
Children diagnosed with FASD may have facial deformities and can exhibit cognitive, behavioral and motor deficits from ethanol-related neurobiological damage in early development. Those deficits may include learning disabilities, reduced intelligence, mental retardation and anxiety or depression, Huffman said.
Milder forms of FASD may produce no facial deformities, such as wideset eyes and smooth upper lip, but behavioral issues such as hyperactivity, hyperirritability and attention problems may appear as the child develops, she added.
Based on her earlier research, Huffman said, she expected to find some disruption of intraneocortical circuitry, but thought it would be subtle.
“I was surprised that the result of alcohol exposure was quite dramatic,” she said. “We found elevated levels of anxiety, disengaged behavior, and difficulty with fine motor coordination tasks. These are the kinds of things you see in children with FASD.”
The next phase of her research will examine whether deficits related to prenatal exposure to alcohol continue in subsequent generations.
The bottom line, Huffman said, is that women who are pregnant or who are trying to get pregnant should abstain from drinking alcohol.
“Would you put whiskey in your baby’s bottle? Drinking during pregnancy is not that much different,” she said. “If you ask me if you have three glasses of wine during pregnancy will your child have FASD, I would say probably not. If you ask if there will be changes in the brain, I would say, probably. There is no safe level of drinking during pregnancy.”
FASD impacts brain development throughout childhood and adolescence not just at birth
Medical researchers at the University of Alberta recently published findings showing that brain development is delayed throughout childhood and adolescence for people born with Fetal Alcohol Spectrum Disorder (FASD).
Christian Beaulieu and Carmen Rasmussen, the two primary investigators in the research study, recently published the results of their work in the peer-reviewed journal, The Journal of Neuroscience. Their team scanned 17 people with FASD, and 27 people without the disorder, who were between 5 and 15 years old. Each participant underwent two to three scans, with each scan taking place two to four years apart. This is the first research study involving multiple scans of the same FASD study participants.
Researchers used an advanced MRI method that examines white matter in the brain. White matter forms connections between various regions of the brain and usually develops significantly during childhood and adolescence. Those who took part in the study were imaged multiple times, to see what kinds of changes occurred in brain development as the participants aged. Those without the disorder had marked increases in brain volume and white matter – growth that was lacking in those with FASD. However, the advanced MRI method revealed greater changes in the brain wiring of white matter in the FASD group, which the authors suggest may reflect compensation for delays in development earlier in childhood.
“These findings may suggest that significant brain changes happened earlier in the study participants who didn’t have FASD,” says the study’s first author, Sarah Treit, who is a student in the Centre for Neuroscience at the U of A. “This study suggests alcohol-induced injury with FASD isn’t static – those with FASD have altered brain development, they aren’t developing at the same rate as those without the disorder. And our research showed those with FASD consistently scored lower on all cognitive measures in the study.”
Treit said the research team also made other important observations. Children with FASD who demonstrated the greatest changes in white matter development also made the greatest gains in reading ability – “so the connection seems relevant.” And those with the most severe FASD showed the greatest changes in white matter brain wiring. Scans also confirmed those with FASD have less overall brain volume – this issue neither rectified itself nor worsened throughout the course of the study.
Beaulieu is a researcher in the Department of Biomedical Engineering, while Rasmussen works in the Department of Pediatrics. Their research was funded by the Canadian Institutes of Health Research.
The team is continuing their research in this area, in hopes of finding a biomarker for FASD, and to examine how the brain changes from adolescence into adulthood in those with the disorder. The advanced MRI imaging the team used can pinpoint brain damage present in those with FASD, and could one day guide medical interventions for those with the disorder, which affects one in every 100 Canadians.
Clues to Fetal Alcohol Risk: Molecular switch promises new targets for diagnosis and therapy
Fetal alcohol syndrome is the leading preventable cause of developmental disorders in developed countries. And fetal alcohol spectrum disorder (FASD), a range of alcohol-related birth defects that includes fetal alcohol syndrome, is thought to affect as many as 1 in 100 children born in the United States.
Any amount of alcohol consumed by the mother during pregnancy poses a risk of FASD, a condition that can include the distinct pattern of facial features and growth retardation associated with fetal alcohol syndrome as well as intellectual disabilities, speech and language delays, and poor social skills. But drinking can have radically different outcomes for different women and their babies. While twin studies have suggested a genetic component to susceptibility to FASD, researchers have had little success identifying who is at greatest risk or what genes are at play.
Research from Harvard Medical School and Veterans Affairs Boston Healthcare System sheds new light on this question, identifying for the first time a signaling pathway that might determine genetic susceptibility for the development of FASD. The study was published online Feb. 19 in the journal Proceedings of the National Academy of Sciences.
“Our work points to candidate genes for FASD susceptibility and identifies a path for the rational development of drugs that prevent ethanol neurotoxicity,” said Michael Charness, chief of staff at VA Boston Healthcare System and HMS professor of neurology. “And importantly, identifying those mothers whose fetuses are most at risk could help providers better target intensive efforts at reducing drinking during pregnancy.”
The discovery also solves a riddle that had intrigued Charness and other researchers for nearly two decades. In 1996, Charness and colleagues discovered that alcohol disrupted the work of a human protein critical to fetal neural development—a major clue to the biological processes of FASD. The protein, L1, projects through the surface of a cell to help it adhere to its neighbors. When Charness and his team introduced the protein to a culture of mouse fibroblasts cells, L1 increased cell adhesion. Tellingly, the effect was erased in the presence of ethanol (beverage alcohol).
Charness and his team went on to develop multiple cell lines from that first culture, and that’s where they encountered the riddle: In some of those lines, alcohol disrupted L1’s adhesive effect, while in others it did not.
“How could it be possible that a cell that expresses L1 is completely sensitive to alcohol, and others that express it are completely insensitive?” asked Charness, who is also faculty associate dean for veterans hospital programs at HMS and assistant dean at Boston University School of Medicine.
Clearly, something else was affecting the protein’s sensitivity to alcohol — but what? Studies of twins provided one clue: Identical twins are more likely than fraternal twins to have the same diagnosis, positive or negative, for FASD. “That concordance suggests that there are modifying genes, susceptibility genes, that predispose to this condition,” Charness said.
The cellular cause of birth defects like cleft palates, missing teeth and problems with fingers and toes has been a tricky puzzle for scientists.
Professor Emily Bates and her biochemistry students at Brigham Young University studied an ion channel that regulates the electrical charge of a cell. In a new study published by the journal Development, they show that blocking this channel disrupts the work of a protein that is supposed to carry marching orders to the nucleus.
Without those instructions, cells don’t become what they were supposed to become – be that part of a palate, a tooth or a finger. Though there are various disorders that lead to birth defects, this newly discovered mechanism may be what some syndromes have in common.
Bates and her graduate student, Giri Dahal, now want to apply the findings toward the prevention of birth defects – particularly those caused by fetal alcohol syndrome and fetal alcohol spectrum disorder.
"What we think might be the case is that this is the target for a few similar disorders," Bates said. "The big thing that we have right now is that this ion channel is required for protein signaling, which means that developmental signaling pathways can sense the charge of a cell. And that’s exciting for a lot of different reasons."
For example, the new study might also have implications for the battle against cancer. With cancer, the problem is that cells are receiving a bad set of instructions that tells them to multiply and spread. If they can devise a way to block the ion channel, it may stop those cancerous instructions from getting through.
"This protein signaling pathway is the same one that tells cancer cells to metastasize," Bates said. "We’re planning to test a therapy to specifically block this channel in just the cells that we want to stop."