Posts tagged autism
Articles and news from the latest research reports.
Deep brain stimulation improves autistic boy’s symptoms
Electrodes implanted deep in the brain of a boy with severe autism have enabled him to live a more normal life. The treatment reduced his destructive behavior and allowed the formerly nonverbal boy to speak a few words, scientists report online January 21 in Frontiers in Human Neuroscience.
The results are the first to use brain stimulation to alleviate symptoms of autism. Scientists caution that interpreting the results broadly is impossible without larger, systematic studies, but even so neurosurgeon Ali Rezai of the Ohio State University Wexner Medical Center in Columbus calls the boys’ gains “intriguing and promising.”
The boy in the study, who was 13 at the time of his experimental surgery, suffered from severe autism symptoms: He couldn’t talk or make eye contact, woke up screaming repeatedly during the night, and habitually injured himself so badly that his parents restrained him almost constantly to protect him. Multiple rounds of psychiatric drugs failed to stave off his worsening symptoms.
In an effort to help him, doctors led by Volker Sturm of the University Hospital of Cologne in Germany implanted electrodes into the boy’s brain. Through trial and error, the doctors realized that stimulating a part of the amygdala, a brain structure important for emotions and memory, improved the boy’s symptoms. Stimulating other brain areas had no effect or worsened his symptoms.
After eight weeks of continuous electrical stimulation, the boy shifted on a clinical scale that measures irritability from “severely ill” to “moderately ill.” The boy also improved on a scale that measures autism symptoms. He began to make eye contact and was better able to control his behavior.
Prenatal inflammation linked to autism risk
Maternal inflammation during early pregnancy may be related to an increased risk of autism in children, according to new findings supported by the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health.Researchers found this in children of mothers with elevated C-reactive protein (CRP), a well-established marker of systemic inflammation.
The risk of autism among children in the study was increased by 43 percent among mothers with CRP levels in the top 20th percentile, and by 80 percent for maternal CRP in the top 10th percentile. The findings appear in the journal Molecular Psychiatry and add to mounting evidence that an overactive immune response can alter the development of the central nervous system in the fetus.
“Elevated CRP is a signal that the body is undergoing a response to inflammation from, for example, a viral or bacterial infection,” said lead scientist on the study, Alan Brown, M.D., professor of clinical psychiatry and epidemiology at Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, and Mailman School of Public Health. “The higher the level of CRP in the mother, the greater the risk of autism in the child.”
Exploring the Brain’s Relationship to Habits
The basal ganglia, structures deep in the forebrain already known to control voluntary movements, also may play a critical role in how people form habits, both bad and good, and in influencing mood and feelings.
"This system is not just a motor system," says Ann Graybiel. "We think it also strongly affects the emotional part of the brain."
Graybiel, an investigator at the McGovern Institute of the Massachusetts Institute of Technology and professor in MIT’s department of brain and cognitive sciences, believes that a core function of the basal ganglia is to help humans develop habits that eventually become automatic, including habits of thought and emotion.
"Many everyday movements become habitual through repetition, but we also develop habits of thought and emotion," she says."If cognitive and emotional habits are also controlled by the basal ganglia, this may explain why damage to these structures can lead not only to movement disorders, but also to repetitive and intrusive thoughts, emotions and desires."
Graybiel’s research focuses on the brain’s relationship to habits—how we make or break them—and the neurobiology of the habit system. She and her team have identified and traced neural loops that run from the outer layer of the brain—“the thinking cap,” as she calls it—to a region called the striatum, which is part of the basal ganglia, and back again. These loops, in fact, connect sensory signals to habitual behaviors.
Her work ultimately could have an impact not just on such classic movement disorders as Parkinson’s and Huntington’s diseases, but in other conditions where repetitive movements commonly occur, such as Tourette Syndrome, autism, or obsessive-compulsive disorder, the latter when sufferers experience unwanted and repeated thoughts, feelings, ideas, sensations or behaviors that make them feel driven to do something, for example, repeatedly washing their hands.
Moreover, the research could have an immediate value for trying to understand “what happens in the brain as addiction occurs, as bad habits form, not just good habits,” she says. “There are many psychiatric and neurologic conditions in which these same brain regions are disordered.
"These conditions may in part be influenced by the very system we are working on," Graybiel adds. "We are working with models of anxiety and depression, stress and some of these movement disorders."
It turns out that the emotional circuits of the brain have strong ties to the striatum, she says. Graybiel’s research suggests that activity in the striatum strongly affects the emotional decisions that people make: whether to accept a good outcome or a potentially bad one, for example, and that there are circuits favoring good outcomes, and, surprisingly, other circuits that favor bad ones.
"This work ties into new research suggesting that there are brain systems for ‘good’ and brain systems for ‘bad,’" she says. "What is intriguing is that we may have identified the circuits that decide between the two."
New Autism-Related Gene Variants Discovered
Genetics researchers have identified 25 additional copy number variations (CNVs)—missing or duplicated stretches of DNA—that occur in some patients with autism. These CNVs, say the researchers, are “high impact”: although individually rare, each has a strong effect in raising an individual’s risk for autism.
“Many of these gene variants may serve as valuable predictive markers,” said the study’s corresponding author, Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics at The Children’s Hospital of Philadelphia. “If so, they may become part of a clinical test that will help evaluate whether a child has an autism spectrum disorder.”
Hakonarson collaborated with scientists from the University of Utah and the biotechnology company Lineagen, Inc., in the study, published in the journal PLOS ONE.
The current study builds on and extends previous gene research by Hakonarson and other scientists on autism spectrum disorders (ASDs), a group of childhood neurodevelopmental disorders that cause impairments in verbal communication, social interaction and behavior. Estimated by the CDC to affect as many as one in 88 U.S. children, ASDs are known from family studies to be strongly influenced by genetics.
Professor Discovers New Information in the Understanding of Autism and Genetics
Research out of the George Washington University (GW), published in the journal Proceedings of the National Academy of Sciences (PNAS), reveals another piece of the puzzle in a genetic developmental disorder that causes behavioral diseases such as autism. Anthony-Samuel LaMantia, Ph.D., professor of pharmacology and physiology at the GW School of Medicine and Health Sciences (SMHS) and director of the GW Institute for Neuroscience, along with post-doctoral fellow Daniel Meechan, Ph.D. and Thomas Maynard, Ph.D., associate research professor of pharmacology and physiology at GW SMHS, authored the study titled “Cxcr4 regulation of interneuron migration is disrupted in 22q11.2 deletion syndrome.”
For the past nine years, LaMantia and his colleagues have been investigating how behavioral disorders such as autism, attention deficit hyperactivity disorder (ADHD), and schizophrenia arise during early brain development. His work published in PNAS focuses specifically on the effects diminished 22q11.2 gene dosage has on cortical circuit development.
This research shows for the first time that genetic lesions known to be associated with autism and other behavioral diseases disrupt cellular and molecular mechanisms that ensure normal development of a key type of cortical neuron: the interneuron. LaMantia and his colleagues had found previously that one type of cortical neuron, the projection neuron, is not generated in appropriate numbers during development in a mouse model of 22q11 Deletion Syndrome. In the current study published in PNAS, LaMantia found that interneurons, while made in the right numbers at their birthplace outside of the cortex, are not able to move properly into the cortex where they are needed to control cortical circuit activity. The research shows that the main reason they don’t move properly is due to diminished expression of activity of a key regulatory pathway for migration, the Cxcr4 cytokine receptor.
“This gives us two pieces of the puzzle for this genetic developmental disorder,” said LaMantia. “These two pieces tell us that in very early development, those with 22q11.2 deletion syndrome do not make enough cells in one case, and do not put the other cells in the right place. This occurs not because of some degenerative change, but because the mechanisms that make these cells and put them in the right place during the first step of development have gone awry due to mutation.”
The next step in LaMantia’s research is to probe further into the molecular mechanisms that disrupt the proliferation of projection neurons and migration of interneurons. “If we understand that better and understand its consequences, we can go about fixing it,” said LaMantia. “We want to understand why cortical circuits don’t get built properly due to the genetic deletion of chromosome 22.”
LaMantia recently received the latest installment of a 10-year RO1 grant from the National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health & Human Development for his project, titled “Regulation of 22q11 Genes in Embryonic and Adult Forebrain.” This will allow him to further his research.
(Image: iStockphoto)
Risk Genes for Alzheimer’s and Mental Illness Linked to Brain Changes at Birth
Some brain changes that are found in adults with common gene variants linked to disorders such as Alzheimer’s disease, schizophrenia, and autism can also be seen in the brain scans of newborns.
“These results suggest that prenatal brain development may be a very important influence on psychiatric risk later in life,” said Rebecca C. Knickmeyer, PhD, lead author of the study and assistant professor of psychiatry in the University of North Carolina School of Medicine. The study was published by the journal Cerebral Cortex on Jan. 3, 2013.
The study included 272 infants who received MRI scans at UNC Hospitals shortly after birth. The DNA of each was tested for 10 common variations in 7 genes that have been linked to brain structure in adults. These genes have also been implicated in conditions such as schizophrenia, bipolar disorder, autism, Alzheimer’s disease, anxiety disorders and depression.
For some polymorphisms – such as a variation in the APOE gene which is associated with Alzheimer’s disease – the brain changes in infants looked very similar to brain changes found in adults with the same variants, Knickmeyer said. “This could stimulate an exciting new line of research focused on preventing onset of illness through very early intervention in at-risk individuals.”
But this was not true for every polymorphism included in the study, said John H. Gilmore, MD, senior author of the study and Thad & Alice Eure Distinguished Professor and Vice Chair for Research and Scientific Affairs in the UNC Department of Psychiatry.
For example, the study included two variants in the DISC1 gene. For one of these variants, known as rs821616, the infant brains looked very similar to the brains of adults with this variant. But there was no such similarity between infant brains and adult brains for the other variant, rs6675281.
“This suggests that the brain changes associated with this gene variant aren’t present at birth but develop later in life, perhaps during puberty,” Gilmore said.
“It’s fascinating that different variants in the same gene have such unique effects in terms of when they affect brain development,” said Knickmeyer.
Dolphin-assisted therapy for children with mental disabilities has made a splash in the West, and China is now riding the experimental tide. Shi Yingying and Erik Nilsson examine the impact these marine mammals have on the children they come into contact with.
Zheng Jun says 15 sessions with a pair of bottle-nosed dolphins at Hangzhou Polar Ocean Park have helped his 5-year-old autistic son become “aware” and “alert” enough to become his kindergarten’s class monitor. The father believes the dolphin-assisted therapy has been more effective than any other treatment. “Now, you can’t tell he’s different from his classmates,” he says. Zheng became a believer after he visited an Australian dolphin-swim program years ago. He says his son is elated when he splashes with the creatures in the park in Zhejiang province’s capital.
More than 80 parents of children with severe mental disabilities have booked all of next year’s spots in the program (sessions only run in the summer because the water temperatures are too cold for the kids in other seasons).
So, newcomers must wait until 2014, says Liu Quansheng, manager of the park’s owner, Zhejiang Aquarium Investment Group. Despite the demand, dolphin-assisted therapy has not been scientifically proven. Still, many experts and parents of special-needs children swear by it.
(Image: dolphin-therapy.org)
Neuroscientists find excessive protein synthesis linked to autistic-like behaviors
Autistic-like behaviors can be partially remedied by normalizing excessive levels of protein synthesis in the brain, a team of researchers has found in a study of laboratory mice. The findings, which appear in the latest issue of Nature, provide a pathway to the creation of pharmaceuticals aimed at treating autism spectrum disorders (ASD) that are associated with diminished social interaction skills, impaired communication ability, and repetitive behaviors.
"The creation of a drug to address ASD will be difficult, but these findings offer a potential route to get there," said Eric Klann, a professor at NYU’s Center for Neural Science and the study’s senior author. "We have not only confirmed a common link for several such disorders, but also have raised the exciting possibility that the behavioral afflictions of those individuals with ASD can be addressed."
The study’s other co-authors included researchers from the University of California, San Francisco (UCSF) and three French institutions: Aix-Marseille Universite’; Institut National de la Santé et de la Recherche Médicale (INSERM); and Le Centre National de la Recherche Scientifique (CNRS).
The researchers focused on the EIF4E gene, whose mutation is associated with autism. The mutation causing autism was proposed to increase levels of the eIF4E, the protein product of EIF4E, and lead to exaggerated protein synthesis. Excessive eIF4E signaling and exaggerated protein synthesis also may play a role in a range of neurological disorders, including fragile X syndrome (FXS).
In their experiments, the researchers examined mice with increased levels of eIF4E. They found that these mice had exaggerated levels of protein synthesis in the brain and exhibited behaviors similar to those found in autistic individuals—repetitive behaviors, such as repeatedly burying marbles, diminished social interaction (the study monitored interactions with other mice), and behavioral inflexibility (the afflicted mice were unable to navigate mazes that had been slightly altered from ones they had previously solved). The researchers also found altered communication between neurons in brain regions linked to the abnormal behaviors.
To remedy to these autistic-like behaviors, the researchers then tested a drug, 4EGI-1, which diminishes protein synthesis induced by the increased levels of eIF4E. Through this drug, they hypothesized that they could return the afflicted mice’s protein production to normal levels, and, with it, reverse autistic-like behaviors.
The subsequent experiments confirmed their hypotheses. The mice were less likely to engage in repetitive behaviors, more likely to interact with other mice, and were successful in navigating mazes that differed from those they previously solved, thereby showing enhanced behavioral flexibility. Additional investigation revealed that these changes were likely due to a reduction in protein production—the levels of newly synthesized proteins in the brains of these mice were similar to those of normal mice.
"These findings highlight an invaluable mouse model for autism in which many drugs that target eIF4E can be tested," added co-author Davide Ruggero, an associate professor at UCSF’s School of Medicine and Department of Urology. "These include novel compounds that we are developing to target eIF4E hyperactivation in cancer that may also be potentially therapeutic for autistic patients."
(Source: eurekalert.org)
Video-based Test to Study Language Development in Toddlers and Children with Autism
Parents often wonder how much of the world their young children really understand. Though typically developing children are not able to speak or point to objects on command until they are between eighteen months and two years old, they do provide clues that they understand language as early as the age of one. These clues provide a point of measurement for psychologists interested in language comprehension of toddlers and young children with autism, as demonstrated in a new video-article published in JoVE (Journal of Visualized Experiments).
In the assessment, psychologists track a child’s eye movements while they are watching two side by side videos. Children who understand language are more likely to look at the video that the audio corresponds to. This way, language comprehension is tested by attention, not by asking the child to respond or point something out. Furthermore, all assessments can be conducted in the child’s home, using mobile, commercially available equipment. The technique was developed in the laboratory of Dr. Letitia Naigles, and is known as a portable intermodal preferential looking assessment (IPL).
"When I started working with children with autism, I realized that they have similar issues with strangers that very young typical children do," Dr. Naigles tells us. "Children with autism may understand more than they can show because they are not socially inclined and find social interaction aversive and challenging." Dr. Naigles’ approach helps make this assessment more valuable. By testing the child in the home, where they are comfortable, Dr. Naigles removes much of the anxiety associated with a new environment that may skew results.
While this technique identifies some similarities between typically developing toddlers and children with autism spectrum disorder, such as understanding some types of sentences before they produce them, this does not mean that these children are the same. “Some strategies of word learning that typical children have acquired are not demonstrated in children with autism.” Dr. Naigles says. By illuminating both strengths and weaknesses, the test is valuable for assessing language development. “JoVE is useful because in the past, I have gone to visit various labs to coach them in putting together an IPL. JoVE will enable other labs to set up the procedure more efficiently.” JoVE associate editor Allison Diamond stated, “Showing this work in a video format will allow other scientists in the field to quickly adapt Dr. Naigles’ technique, and use it to address the question of language development in autism, an extremely important field of research.”
Fragile X Protein Linked to Nearly 100 Genes Involved in Autism
Doctors have known for many years that patients with fragile X syndrome, the most common form of inherited intellectual disability, are often also diagnosed with autism. But little has been known about how the two diagnoses are related.
Now a collaborative research effort at Duke University Medical Center and Rockefeller University has pinpointed the precise genetic footprint that links the two. The findings, published online in the journal Nature on Dec. 12, 2012, point the way toward new genetic testing that could more precisely diagnose and categorize the spectrum of autism-related disorders.
Fragile X syndrome is the most well understood single-gene cause of autism. It results from defects on a small part of the genetic code for a protein that researchers have dubbed the fragile X mental retardation protein, or FMRP.
Normally, FMRP plays an important role controlling production of other proteins in the brain and other organs. It does this by looking for specific genetic patterns located on the messages encoding proteins. When it locates these genetic flags, it attaches to them and, along with other signals, controls where and when protein is made.
In fragile X syndrome, this process breaks down because a defect in the gene causes the body to produce too little, or in some cases, none of the FMRP protein. As a result, additional proteins it would normally regulate are made in the wrong place and at the wrong time. Until now, little was known about how this process worked in people with the autism.
Using a combination of laboratory experiments and advanced bioinformatics, the research team, led by Thomas Tuschl, PhD, a Howard Hughes Medical Institute investigator at Rockefeller University, and Uwe Ohler, PhD, an associate professor in Biostatistics and Bioinformatics at the Duke Institute for Genome Sciences & Policy, identified both the genetic flags that FMRP is looking for and the genes it targets.
(Image courtesy of www.sueblimely.com)