Posts tagged autism
Articles and news from the latest research reports.
When fear factors in
A little bit of learned fear is a good thing, keeping us from making risky, stupid decisions or falling over and over again into the same trap. But new research from neuroscientists and molecular biologists at USC shows that a missing brain protein may be the culprit in cases of severe over-worry, where the fear perseveres even when there’s nothing of which to be afraid.
In a study appearing the week of July 15 in the Proceedings of the National Academy of Sciences, the researchers examined mice without the enzymes monoamine oxidase A and B (MAO A/B), which sit next to each other in a human’s genetic code as well as on that of mice. Prior research has found an association between deficiencies of these enzymes in humans and developmental disabilities along the autism spectrum, such as clinical perseverance, the inability to change or modulate actions along with social context.
“These mice may serve as an interesting model to develop interventions to these neuropsychiatric disorders,” said University Professor and senior author Jean Shih, Boyd & Elsie Welin Professor of Pharmacology and Pharmaceutical Sciences at the USC School of Pharmacy and the Keck School of Medicine of USC. “The severity of the changes in the MAO A/B knockout mice compared to MAO A knockout mice supports the idea that the severity of autistic-like features may be correlated to the amounts of monoamine levels, particularly at early developmental stages.”
Shih is a world leader in understanding the neurobiological and biochemical mechanisms behind such behaviors as aggression and anxiety. In this latest study, Shih and her co-investigators — including lead author Chanpreet Singh, a USC doctoral student at the time of the research who is now at the California Institute of Technology (Caltech), and Richard Thompson, USC University Professor Emeritus and Keck Professor of Psychology and Biological Sciences at the USC Dornsife College of Letters, Arts and Sciences — expanded their past research on MAO A/B, which regulates neurotransmitters known as monoamines, including serotonin, norepinephrine and dopamine.
Comparing mice without MAO A/B with their wild-type littermates, the researchers found significant differences in how the mice without MAO A/B processed fear and other types of learning. Mice without MAO A/B and wild mice were put in a new, neutral environment and given a mild electric shock. All mice showed learned fear the next time they were tested in the same environment, with the MAO A/B knockout mice displaying a greater degree of fear.
But while wild mice continued to explore other new environments freely after the trauma, mice without the MAO A/B enzymes generalized their phobia to other contexts — their fear spilled over onto places where they should have no reason to be afraid.
“The neural substrates processing fear in the brain is very different in these mice,” Singh said. “Enhanced learning in the wrong context is a disorder and is exemplified by these mice. Their brain is not letting them forget. In a survival issue, you need to be able to forget things.”
The mice without MAO A and MAO B also learned eye-blink conditioning much more quickly than wild mice, which has also been noted in autistic patients but not in mice missing only one of these enzymes.
Importantly, the mice without MAO A/B did not display any differences in learning for spatial skills and object recognition, the researchers found, “but in their ability to learn an emotional event, the [MAO A/B knockout mice] are very different than wild types,” Singh said.
He continued: “When both enzymes are missing, it significantly increases the levels of neurotransmitters, which causes developmental changes, which leads to differential expression of receptors that are very important for synaptic plasticity — a measure of learning — and to behavior that is quite similar to what we see along the autism spectrum.”
(Source: news.usc.edu)
Foraging for thought – new insights into our working memory
We take it for granted that our thoughts are in constant turnover. Metaphors like “stream of consciousness” and “train of thought” imply steady, continuous motion. But is there a mechanism inside our heads that drives this? Is there something compelling our attention to move on to new ideas instead of dwelling in the same spot forever?
A research team led by Dr Matthew Johnson in the School of Psychology at The University of Nottingham Malaysia Campus (UNMC) may have discovered part of the answer. They have pinpointed an effect that makes people turn their attention to something new rather than dwelling on their most recent thoughts. The research, which has been published in the academic journal Psychological Science, could have implications for studying disorders like autism and ADHD.
Dr Johnson said: “We have discovered a very promising paradigm. The effect is strong and replicates easily – you could demonstrate it in any psychology lab in the world. The work is still in its early stages but I think this could turn out to be a very important part of our understanding of how and why our thoughts work the way they do.
The paper “Foraging for Thought: An Inhibition-of-Return-Like Effect Resulting From Directing Attention Within Working Memory” sheds new light on what makes us turn our attention to things we haven’t recently thought rather than ones we have. It was carried out in collaboration with Yale University, Princeton University, The Ohio State University, and Manhattanville College.
The “inhibition of return” effect is well-established in visual attention. At certain time scales, people are slower to turn their thoughts back to a location they have just paid attention to. They are much quicker to focus on a new location. Some have interpreted this effect as a “foraging facilitator,” a process that encourages organisms to visit new locations over previously visited ones when exploring a new environment or performing a visual search.
However, in this new study, the researchers weren’t focusing on visual search, but on the process of thought itself. Participants were shown either two words or two pictures, and when the items disappeared, they were instructed to turn their attention briefly to one of the items they were just shown and ignore the other. Immediately afterwards they were asked to identify either the item they had just thought about, or the one they had ignored. For both pictures and words the participants were quicker to react to the item they had ignored.
Dr Johnson said: “The effect was shocking. When we began we expected to find the exact opposite – that thinking about something will make it easier to identify. We were initially disappointed – but when the effect was replicated over multiple experiments we realised we were onto something new and exciting.”
Critically, the effect is temporary; on a later memory test participants remembered attended items better than ignored ones.
Dr Johnson said: “That’s important. If thinking about things made us worse at remembering them long-term, it would make no sense for real-world survival. That’s why we think we’ve tapped into something fundamental about how we think in the moment – a possible mechanism keeping our thoughts moving onto new things, and not getting stuck.”
The researchers have more experiments planned to explore this effect. They say the new task could have implications for studying disorders like autism and ADHD, where attention may persist too long or move on too easily, as well as conditions with more general cognitive impairments, such as schizophrenia and ageing-related dementia.
Future studies planned also include applying cognitive neuroscience techniques to determine the effect’s underlying neural foundations.
(Source: nottingham.ac.uk)
Autism Speaks Collaborative Releases First Full Genome Sequencing for Autism Spectrum Disorders
A collaborative formed by Autism Speaks, the world’s leading autism science and advocacy organization, has found full genome sequencing examining the entire DNA code of individuals with autism spectrum disorder (ASD) and their family members to provide the definitive look at the wide ranging genetic variations associated with ASD. The study published online today in American Journal of Human Genetics, reports on full genome sequencing on 32 unrelated Canadian individuals with autism and their families, participants in the Autism Speaks Autism Genetic Resource Exchange (AGRE). The results include both inherited as well as spontaneous or de novo, genetic alterations found in one half of the affected families sequenced.
This dramatic finding of genetic risk variants associated with clinical manifestation of ASD or accompanying symptoms in 50 percent of the participants tested is promising, as current diagnostic technology has only been able to determine a genetic basis in about 20 percent of individuals with ASD tested. The large proportion of families identified with genetic alterations of concern is in part due to the comprehensive and uniform ability to examine regions of the genome possible with whole genome sequencing missed in other lower resolution genome scanning approaches.
"From diagnosis to treatment to prevention, whole genome sequencing efforts like these hold the potential to fundamentally transform the future of medical care for people with autism," stated Autism Speaks Chief Science Officer and study co-author Robert Ring, Ph.D.
The study identified genetic variations associated with risk for ASD including de novo, X-linked and other inherited DNA lesions in four genes not previously recognized for ASD; nine genes previously determined to be associated with ASD risk; and eight candidate ASD risk genes. Some families had a combination of genes involved. In addition, risk alterations were found in genes associated with fragile X or related syndromes (CAPRIN1 and AFF2), social-cognitive deficits (VIP), epilepsy (SCN2A and KCNQ2) as well as NRXN1 and CHD7, which causes ASD-associated CHARGE syndrome.
“Whole genome sequencing offers the ultimate tool to advance the understanding of the genetic architecture of autism,” added lead author Dr. Stephen Scherer, senior scientist and director of the Centre for Applied Genomics at The Hospital for Sick Children (SickKids) and director of the McLaughlin Centre at the University of Toronto. “In the future, results from whole genome sequencing could highlight potential molecular targets for pharmacological intervention, and pave the way for individualized therapy in autism. It will also allow for earlier diagnosis of some forms of autism, particularly among siblings of children with autism where recurrence is approximately 18 per cent.”
This $1 million collaboration of Autism Speaks, SickKids, BGI and Duke University piloted Autism Speaks’ initiative to generate the world’s largest library of sequenced genomes of individuals with ASD announced in late 2011. “As we continue to test more individuals and their family members from the AGRE cohort, we expect to discover and study additional genetic variants associated with autism. This collaboration will accelerate basic and translational research in autism and related developmental disabilities,” concluded Autism Speaks Vice President for Scientific Affairs Andy Shih, Ph.D. who oversees the collaboration, “and this collection of sequenced genomes will facilitate new collaborations engaging researchers around the world, and enable public and private entities to pursue pivotal research.”
In this pilot effort, a total of 99 individuals were tested, including the 32 individuals with ASD (25 males and seven females) and their two parents, as well as three members of one control family not on the autism spectrum. Using families in the Autism Speaks AGRE collection, this Autism Speaks initiative will ultimately perform whole genome sequencing on more than 2,000 participating families who have two or more children on the autism spectrum. The data from the 10,000 AGRE participants will enable new research in the genomics of ASD, and significantly enhance the science and technology networks of Autism Speaks and its collaborators.
(Source: autismspeaks.org)
Children who were later diagnosed with autism spectrum disorder had excessive cerebrospinal fluid and enlarged brains in infancy, a study by a multidisciplinary team of researchers with the UC Davis MIND Institute has found, raising the possibility that those brain anomalies may serve as potential biomarkers for the early identification of the neurodevelopmental disorder.
The study is the first to follow the brain-growth trajectories from infancy in children who later develop autism and the first to associate excessive cerebrospinal fluid during infancy with autism. “Early Brain Development and Elevated Extra-Axial Fluid in Infants who Develop Autism Spectrum Disorder,” is published online today in the neurology journal Brain, published by Oxford University Press.
"This is the first report of an infant brain anomaly associated with autism that is detectable by using conventional structural MRI,” said MIND Institute Director of Research David Amaral, who co-led the study.
"This study raises the potential of developing a very early method of detecting autism spectrum disorder. Early detection is critical, because early intervention can decrease the cognitive and behavioral impairments associated with autism and may result in more positive long-term outcomes for the child,” Amaral said.
The study was conducted in 55 infants between 6 and 36 months of age, 33 of whom had an older sibling with autism. Twenty-two infants were children with no family history of the condition.
The researchers reported that the brain anomaly was detected significantly more often in the high-risk infants who were later diagnosed with autism between 24 and 36 months. Prior research by Sally Ozonoff, the vice chair for research and professor in the Department of Psychiatry and Behavioral Sciences, who co-led the study, has shown that the risk of autism is nearly 20 times greater in siblings of children with autism than in the general population. The U. S. Centers for Disease Control and Prevention puts the overall incidence of autism at 1 in 88.
The excessive cerebrospinal fluid and enlarged brain volume were detected by periodically measuring the infants’ brain growth and development using magnetic resonance imaging (MRI), and by regularly assessing their cognitive, social, communication and motor development. Both the high- and low-risk infants underwent their first MRI scans at 6 to 9 months. The second MRI scans occurred when they were 12 to 15 months old. The third was conducted between 18 and 24 months. The MRIs were conducted while the infants were sleeping naturally, without the need for sedation or anesthesia.
At 6 months, the researchers began intensive behavioral assessments of the infants’ development. Their parents also periodically completed questionnaires about their babies’ behaviors. These tests were conducted until the infants were 24 to 36 months old, when each child was evaluated as having autism spectrum disorder, other developmental delays, or typical development.
In addition to the 10 children diagnosed with autism, 24 percent of the high-risk and 13.5 percent of the low-risk infants were classified as having other developmental delays. Some 45.5 percent of high-risk and over 86 percent of low-risk babies were found to be developing normally.
The researchers found that by 6 to 9 months of age, the children who developed autism had elevated cerebrospinal fluid levels in the “extra-axial” space above and surrounding the brain, and that those fluid levels remained abnormally elevated between 18 to 24 months of age. The more fluid during early infancy, the more severe were the child’s autism symptoms when diagnosed, the study found.
In the infants who would go on to be diagnosed with autism, the ”extra-axial” fluid volume was, on average, 33 percent greater at 12 to 15 months and 22 percent greater at 18 to 24 months, when compared with typically developing infants. At 6 to 9 months, the extra-axial fluid volume was 20 percent greater, when compared with typically developing infants.
The study also provided the first MRI evidence of brain enlargement in autism prior to 24 months. The infants in the study diagnosed with autism had, on average, 7 percent larger brain volumes at 12 months, compared with the typically developing infants.
The excessive extra-axial fluid and enlarged brain volume were detected by brain imaging before behavioral signs of autism were evident. “The cause of the increased extra-axial fluid and enlarged brain size is currently unknown”, Amaral said.
Early diagnosis may be of particular benefit to infants whose older siblings have been diagnosed with autism, but the researchers caution that this finding must be replicated before it could aid in the early diagnosis of ASD. The MIND Institute is currently collaborating with other research institutions to replicate these findings and to evaluate how well the potential biomarker can accurately predict a later diagnosis of ASD.
“It is critical to understand how often this brain finding is present in children who do not develop autism, as well,” said Ozonoff. “For a biomarker to be useful in predicting autism outcomes, we want to be sure it does not produce an unacceptable level of false positives.”
“If this finding of elevated extra-axial fluid is replicated in a larger sample of infants who develop autism, and it accurately distinguishes between infants who do not develop autism, it has the potential of becoming a noninvasive biomarker that would aid in early detection, and ultimately improve the long-term outcomes of these children through early intervention,” said Mark Shen, UC Davis graduate student and the study’s lead author.
Breakthrough Study Reveals Biological Basis for Sensory Processing Disorders in Kids
Sensory processing disorders (SPD) are more prevalent in children than autism and as common as attention deficit hyperactivity disorder, yet it receives far less attention partly because it’s never been recognized as a distinct disease.
In a groundbreaking new study from UC San Francisco, researchers have found that children affected with SPD have quantifiable differences in brain structure, for the first time showing a biological basis for the disease that sets it apart from other neurodevelopmental disorders.
One of the reasons SPD has been overlooked until now is that it often occurs in children who also have ADHD or autism, and the disorders have not been listed in the Diagnostic and Statistical Manual used by psychiatrists and psychologists.
“Until now, SPD hasn’t had a known biological underpinning,” said senior author Pratik Mukherjee, MD, PhD, a professor of radiology and biomedical imaging and bioengineering at UCSF. “Our findings point the way to establishing a biological basis for the disease that can be easily measured and used as a diagnostic tool,” Mukherjee said.
The work is published in the open access online journal NeuroImage:Clinical.
‘Out of Sync’ Kids
Sensory processing disorders affect 5 to 16 percent of school-aged children.
Children with SPD struggle with how to process stimulation, which can cause a wide range of symptoms including hypersensitivity to sound, sight and touch, poor fine motor skills and easy distractibility. Some SPD children cannot tolerate the sound of a vacuum, while others can’t hold a pencil or struggle with social interaction. Furthermore, a sound that one day is an irritant can the next day be sought out. The disease can be baffling for parents and has been a source of much controversy for clinicians, according to the researchers.
“Most people don’t know how to support these kids because they don’t fall into a traditional clinical group,” said Elysa Marco, MD, who led the study along with postdoctoral fellow Julia Owen, PhD. Marco is a cognitive and behavioral child neurologist at UCSF Benioff Children’s Hospital, ranked among the nation’s best and one of California’s top-ranked centers for neurology and other specialties, according to the 2013-2014 U.S. News & World Report Best Children’s Hospitals survey.
“Sometimes they are called the ‘out of sync’ kids. Their language is good, but they seem to have trouble with just about everything else, especially emotional regulation and distraction. In the real world, they’re just less able to process information efficiently, and they get left out and bullied,” said Marco, who treats affected children in her cognitive and behavioral neurology clinic.
“If we can better understand these kids who are falling through the cracks, we will not only help a whole lot of families, but we will better understand sensory processing in general. This work is laying the foundation for expanding our research and clinical evaluation of children with a wide range of neurodevelopmental challenges – stretching beyond autism and ADHD,” she said.
Imaging the Brain’s White Matter
In the study, researchers used an advanced form of MRI called diffusion tensor imaging (DTI), which measures the microscopic movement of water molecules within the brain in order to give information about the brain’s white matter tracts. DTI shows the direction of the white matter fibers and the integrity of the white matter. The brain’s white matter is essential for perceiving, thinking and learning.
The study examined 16 boys, between the ages of eight and 11, with SPD but without a diagnosis of autism or prematurity, and compared the results with 24 typically developing boys who were matched for age, gender, right- or left-handedness and IQ. The patients’ and control subjects’ behaviors were first characterized using a parent report measure of sensory behavior called the Sensory Profile.
The imaging detected abnormal white matter tracts in the SPD subjects, primarily involving areas in the back of the brain, that serve as connections for the auditory, visual and somatosensory (tactile) systems involved in sensory processing, including their connections between the left and right halves of the brain.
“These are tracts that are emblematic of someone with problems with sensory processing,” said Mukherjee. “More frontal anterior white matter tracts are typically involved in children with only ADHD or autistic spectrum disorders. The abnormalities we found are focused in a different region of the brain, indicating SPD may be neuroanatomically distinct.”
The researchers found a strong correlation between the micro-structural abnormalities in the white matter of the posterior cerebral tracts focused on sensory processing and the auditory, multisensory and inattention scores reported by parents in the Sensory Profile. The strongest correlation was for auditory processing, with other correlations observed for multi-sensory integration, vision, tactile and inattention.
The abnormal microstructure of sensory white matter tracts shown by DTI in kids with SPD likely alters the timing of sensory transmission so that processing of sensory stimuli and integrating information across multiple senses becomes difficult or impossible.
“We are just at the beginning, because people didn’t believe this existed,” said Marco. “This is absolutely the first structural imaging comparison of kids with research diagnosed sensory processing disorder and typically developing kids. It shows it is a brain-based disorder and gives us a way to evaluate them in clinic.”
Future studies need to be done, she said, to research the many children affected by sensory processing differences who have a known genetic disorder or brain injury related to prematurity.
Clues about autism may come from the gut
Bacterial flora inhabiting the human gut have become one of the hottest topics in biological research. Implicated in a range of important activities including digestion, fine-tuning body weight, regulating immune response, and producing neurotransmitters that affect brain and behavior, these tiny workers form diverse communities. Hundreds of species inhabit the gut, and although most are beneficial, some can be very dangerous.
In new research appearing in the journal PLOS ONE, a team led by Rosa Krajmalnik-Brown, a researcher at Arizona State University’s Biodesign Institute, present the first comprehensive bacterial analysis focusing on commensal or beneficial bacteria in children with autism spectrum disorder (ASD).
After publishing earlier research exploring crucial links between intestinal microflora and gastric bypass, Krajmlanik-Brown convinced James Adams— director of the ASU Autism/Asperger’s Research Program—that similar high throughput techniques could be used to mine the microbiome of patients with autism. (Previously, Adams had been studying the relationship between the gut microbiome and autism using traditional culturing techniques.)
“One of the reasons we started addressing this topic is the fact that autistic children have a lot of GI problems that can last into adulthood,” Krajmalnik-Brown says. “Studies have shown that when we manage these problems, their behavior improves dramatically.”
Following up on these tantalizing hints, the group hypothesized the existence of distinctive features in the intestinal microflora found in autistic subjects compared to typical children. The current study confirmed these suspicions, and found that children with autism had significantly fewer types of gut bacteria, probably making them more vulnerable to pathogenic bacteria. Autistic subjects also had significantly lower amounts of three critical bacteria, Prevotella, Coprococcus, and Veillonellaceae.
Krajmalnik-Brown, along with the paper’s lead authors Dae-Wook Kang and Jin Gyoon Park, suggest that knowledge gleaned through such research may ultimately be used both as a quantitative e diagnostic tool to pinpoint autism and as a guide to developing effective treatments for ASD-associated GI problems. The work also offers hope for new prevention and treatment methods for ASD itself, which has been on a mysterious and rapid ascent around the world.
A disquieting puzzle
Autism is defined as a spectrum disorder, due to the broad range of symptoms involved and the influence of both genetic and environmental factors, features often confounding efforts at accurate diagnosis. The diseases’ prevalence in children exceeds juvenile diabetes, childhood cancer and pediatric AIDS combined.
Controversy surrounds the apparent explosive rise in autism cases. Heightened awareness of autism spectrum disorders and more diligent efforts at diagnosis must account for some of the increase, yet many researchers believe a genuine epidemic is occurring. In addition to hereditary components, Western-style diets and overuse of antibiotics at an early age may be contributing to the problem by lowering the diversity of the gut microflora.
In terms of severe developmental ailments affecting children and young adults, autism is one of the most common, striking about 1 in 50 children. The disorder—often pitiless and perplexing—is characterized by an array of physical and behavioral symptoms including anxiety, depression, extreme rigidity, poor social functioning and an overall lack of independence.
To date, studies of the gut microbiome in autistic subjects have focused primarily on pathogenic bacteria, some of which have been implicated in alterations to brain function. One example involves gram-negative bacteria containing lipopolysaccharides in their cell walls, which can induce inflammation of the brain and lead to the accumulation of high levels of mercury in the cerebrum.
A new approach
Krajmalnik-Brown and lead author Dae-Wook Kang are researchers in the Biodesign Institute’s Swette Center for Environmental Biotechnology, which is devoted to the use of microbial communities for the benefit of human and environmental health. Their new study is the first to approach autism from a different angle, by examining the possible role of so-called commensal or beneficial bacteria.
Up to a quadrillion (1014) bacteria inhabit the human intestine, contributing to digestion, producing vitamins and promoting GI health. Genes associated with human intestinal flora are 100 times as plentiful as the body’s human genes, forming what some have referred to as a second genome. Various environmental factors can destabilize the natural microbiome of the gut, including antibiotics and specific diets.
In the current study, a cohort of 20 healthy and 20 autistic subjects between 3 and 16 years of age were selected and their gut microflora from fecal samples analyzed by means of a technique known as pyrosequencing. Pyrosequencing is a high-throughput method, allowing many DNA samples to be combined as well as many sequences per sample to be analyzed.
Lower diversity of gut microbes was positively correlated with the presence of autistic symptoms in the study. The authors stress that bacterial richness and diversity are essential for maintaining a robust and adaptable bacterial community capable of fighting off environmental challenges. “We believe that a diverse gut is a healthy gut,” Krajmalnik-Brown says.
The new study detected decreased microbial diversity in the 20 autistic subjects whose fecal samples were analyzed. Specifically, three bacterial genera—Prevotella, Coprococcus and Veillonellaceae—were diminished in subjects with autism, when compared with samples from normal children. (Surprisingly, these microbial changes did not seem directly correlated with the severity of GI symptoms.)
The three genera represent important groups of carbohydrate-degrading and/or fermenting microbes. Such bacteria could be critical for healthy microbial-gut interactions or play a supportive role for a wide network of different microorganisms in the gut. The latter would explain the decreased diversity observed in autistic samples.
Bacteria: in sickness and in health
Among the fully classified genera in the study, Prevotella was the most conspicuously reduced in autistic subjects. Prevotella is believed to play a key role in the composition of the human gut microbiome. For this reason, the group undertook a sub-genus investigation of autistic subjects. They found that a species known as Prevotella copri occurred only in very low levels in the autistic samples. The species is a common component in normal children exhibiting more diverse and robust microbial communities.
“We think of Prevotella as a healthy, good thing to have,” Krajmalnik-Brown notes. (Michael Polan’s recent New York Times Magazine story on the microbiome points to the fact that he is proud that his gut microbiome is rich in Prevotella regarding it as a possible sign of a healthy non-Western diet. )
Jin Gyoon Park (the other lead author), who works in the Virginia G. Piper Center for Personalized Diagnostics, under Joshua LaBaer’s direction, conducted a rigorous bioinformatic and statistical analysis of the intestinal microflora. He believes that the microbiome can be mined in future work to find diagnostic biomarkers for autism and many other diseases. Quantitative diagnoses of this sort have so far been lacking for autism, a disease for which subjective behavior indices are typically used to identify the disorder.
In describing the next steps for the research group, Kang and Park point to more detailed, gene-level analyses aimed at probing bacterial function and further illuminating relationships between human health and the complexities of the microbiome. Additionally, the group will use the current results as a guide for new treatment studies for autism aimed at modifying bacterial composition in the gut.
IVF for male infertility linked to increased risk of intellectual disability and autism in children
In the first study to compare all available IVF treatments and the risk of neurodevelopmental disorders in children, researchers find that IVF treatments for the most severe forms of male infertility are associated with an increased risk of intellectual disability and autism in children.
Autism and intellectual disability remain a rare outcome of IVF, and whilst some of the risk is associated with the risk of multiple births, the study provides important evidence for parents and clinicians on the relative risks of modern IVF treatments.
Published in JAMA today, the study is the largest of its kind and was led by researchers at King’s College London (UK), Karolinska Institutet (Sweden) and Mount Sinai School of Medicine in New York (USA).
By using anonymous data from the Swedish national registers, researchers analysed more than 2.5 million birth records from 1982 and 2007 and followed-up whether children had a clinical diagnosis of autism or intellectual disability (defined as having an IQ below 70) up until 2009. Of the 2.5m children, 1.2% (30,959) were born following IVF. Of the 6,959 diagnosed with autism, 103 were born after IVF; of the 15,830 with intellectual disability, 180 were born after IVF. Multiple pregnancies are a known risk factor for pre-term birth and some neurodevelopmental disorders, so the researchers also compared single to multiple births.
Sven Sandin, co-author of the study from King’s College London’s Institute of Psychiatry says: “IVF treatments are vastly different in terms of their complexity. When we looked at IVF treatments combined, we found there was no overall increased risk for autism, but a small increased risk of intellectual disability. When we separated the different IVF treatments, we found that ‘traditional’ IVF is safe, but that IVF involving ICSI, which is specifically recommended for paternal infertility is associated with an increased risk of both intellectual disability and autism in children.”
Compared to spontaneous conception, children born from any IVF treatment were not at an increased risk of autism, but were at a small increased risk of intellectual disability (18% increase – from 39.8 to 46.3 per 100,000 person years). However, the risk increase disappeared when multiple births were taken into account.
Secondly, the researchers compared all 6 different types of IVF procedures available in Sweden – whether fresh or frozen embryos were used; if intracytoplasmic sperm injection (ICSI) was used, and if so, whether sperm was ejaculated or surgically extracted. Developed in 1992, ICSI is recommended for male infertility and is now used in about half of all IVF treatments. The procedure involves injecting a single sperm directly into an egg, rather than fertilization happening in a dish, as in standard IVF.
Children born after IVF treatments with ICSI (with either fresh or frozen embryos) were at an increased risk of intellectual disability (51% increase – 62 to 93 per 100,000). This association was even higher when a preterm birth also occurred (73% increase – 96 to 167 per 100,000). Even when multiple and pre-term births were taken into account, IVF treatment with ICSI and fresh embryos was associated with an increased risk of intellectual disability (66% increase for singleton birth, term birth following ICSI with fresh embryos– 48 to 76 per 100,000).
Children born after IVF with ICSI using surgically extracted sperm and fresh embryos were at an increased risk of autism (360% increase - 29 to 136 per 100,000) but the association disappeared when multiple births were taken into account.
(Source: kcl.ac.uk)
Children with delayed motor skills struggle more socially
Studies have shown that children with autism often struggle socially and now new research suggests that a corresponding lack of motor skills – including catching and throwing – may further contribute to that social awkwardness.
The findings, published in the July issue of Adapted Physical Activity Quarterly, add to the growing body of research highlighting the link between autism and motor skill deficits.
Lead author Megan MacDonald is an assistant professor in the College of Public Health and Human Sciences at Oregon State University. She is an expert on the movement skills of children with autism spectrum disorder.
In the study, researchers looked a group of young people ages 6 to 15 diagnosed with autism spectrum disorder. All 35 of the students were considered high-functioning and attended typical classrooms. The researchers looked at two types of motor skills – “object-control” motor skills, which involve more precise action such as catching or throwing – and “locomotion” skills, such as running or walking. Students who struggled with object-control motor skills were more likely to have more severe social and communication skills than those who tested higher on the motor skills test.
“So much of the focus on autism has been on developing social skills, and that is very crucial,” MacDonald said. “Yet we also know there is a link between motor skills and autism, and how deficits in these physical skills play into this larger picture is not clearly understood.”
Developing motor skills can be crucial for children because students often “mask” their inability to participate in basic physical activities. A student with autism may not be participating on the playground because of a lack of social skills, but the child may also be unsure of his or her physical ability to play in these activities.
“Something which seems as simple as learning to ride a bike can be crucial for a child with autism,” MacDonald said. “Being able to ride a bike means more independence and autonomy. They can ride to the corner store or ride to a friend’s house. Those kind of small victories are huge.”
She said the ability to run, jump, throw and catch isn’t just for athletic kids – physical activity is linked not only to health, but to social skills and mental well-being.
“I often show people photos of what I like to do in my spare time – canoeing, hiking, snowshoeing, and then point out that these require relatively proficient motor skills,” she said. “But that is not why I do those things. I’m doing it because I’m with my friends and having fun.”
MacDonald said the positive news for parents and educators is that motor skills can be taught.
“We have programs and interventions that we know work, and have measurable impact on motor skill development,” MacDonald said. “We need to make sure we identify the issue and get a child help as early as possible.”
(Source: oregonstate.edu)
An SDSU research team has discovered that autism in children affects not only social abilities, but also a broad range of sensory and motor skills.
A group of investigators from San Diego State University’s Brain Development Imaging Laboratory are shedding a new light on the effects of autism on the brain.
The team has identified that connectivity between the thalamus, a deep brain structure crucial for sensory and motor functions, and the cerebral cortex, the brain’s outer layer, is impaired in children with autism spectrum disorders (ASD).
Led by Aarti Nair, a student in the SDSU/UCSD Joint Doctoral Program in Clinical Psychology, the study is the first of its kind, combining functional and anatomical magnetic resonance imaging (fMRI) techniques and diffusion tensor imaging (DTI) to examine connections between the cerebral cortex and the thalamus.
Nair and Dr. Ralph-Axel Müller, an SDSU professor of psychology who was senior investigator of the study, examined more than 50 children, both with autism and without.
Brain communication
The thalamus is a crucial brain structure for many functions, such as vision, hearing, movement control and attention. In the children with autism, the pathways connecting the cerebral cortex and thalamus were found to be affected, indicating that these two parts of the brain do not communicate well with each other.
“This impaired connectivity suggests that autism is not simply a disorder of social and communicative abilities, but also affects a broad range of sensory and motor systems,” Müller said.
Disturbances in the development of both the structure and function of the thalamus may play a role in the emergence of social and communicative impairments, which are among the most prominent and distressing symptoms of autism.
While the findings reported in this study are novel, they are consistent with growing evidence on sensory and motor abnormalities in autism. They suggest that the diagnostic criteria for autism, which emphasize social and communicative impairment, may fail to consider the broad spectrum of problems children with autism experience.
The study was supported with funding from the National Institutes of Health and additional funding from Autism Speaks Dennis Weatherstone Predoctoral Fellowship. It was published in the June issue of the journal, BRAIN.
Genes Involved in Birth Defects May Also Lead to Mental Illness
Gene mutations that lead to major birth defects may also cause subtle disruptions in the brain that contribute to psychiatric disorders such as schizophrenia, autism, and bipolar disorder, according to new research by UC San Francisco scientists.
Over the past several years, researchers in the laboratory of psychiatrist Benjamin Cheyette, MD, PhD, have shown that mutations in a gene called Dact1 cause cell signaling networks to go awry during embryonic development. Researchers observed that mice with Dact1 mutations were born with a range of severe malformations, including some reminiscent of spina bifida in humans.
This new study was designed to explore whether Dact1 mutations exert more nuanced effects in the brain that may lead to mental illness. In doing so, Cheyette, John Rubenstein, MD, PhD, and colleagues in UCSF’s Nina Ireland Laboratory of Developmental Neurobiology used a genetic technique in adult mice to selectively delete the Dact1 protein only in interneurons, a group of brain cells that regulates activity in the cerebral cortex, including cognitive and sensory processes. Poor function of interneurons has been implicated in a range of psychiatric conditions.
As reported in the June 24 online issue of PLOS ONE, researchers found that the genetically altered interneurons appeared relatively normal and had managed to find their proper position in the brain’s circuitry during development. But the cells had significantly fewer synapses, the sites where communication with neighboring neurons takes place. In additional observations not included in the new paper, the team also noted that the cells’ dendrites – fine extensions that normally form bushy arbors studded with synapses – were poorly developed and sparsely branched.
“When you delete this gene function after initial, early development – just eliminating it in neurons after they’ve formed – they migrate to the right place and their numbers are correct, but their morphology is a little off,” Cheyette said. “And that’s very much in line with the kinds of pathology that people have been able to identify in psychiatric illness.
"Neurological illnesses tend to be focal, with lesions that you can identify or pathology you can see on an imaging study," Cheyette explained. "Psychiatric illnesses? Not so much. The differences are really subtle and hard to see.”
Key Gene’s Role in Development of Human Nervous System
The Dact1 protein is part of a fundamental biological system known as the Wnt (pronounced “wint”) signaling pathway. Interactions among proteins in the Wnt pathway orchestrate many processes essential to life in animals as diverse as fruit flies, mice and humans, including the proper development of the immensely complex human nervous system from a single fertilized egg cell.
One way the Wnt pathway manages this task is by maintaining the “polarity” of cells during development, said Cheyette, “a process of sequestering, increasing the concentration of one set of proteins on one side of the cell and a different set of proteins on the other side of the cell.” Polarity is particularly important as precursor cells transform into nerve cells, Cheyette said, because neurons are “the most polarized cells in the body,” with specialized input and output zones that must wind up in the proper spots if the cells are to function normally.
Cheyette said his group is now conducting behavioral experiments with the mice analyzed in the new PLOS ONE paper and with genetically related mouse lines to test whether these mice have behavioral abnormalities in sociability, sensory perception, anxiety or motivation that resemble symptoms in major psychiatric disorders.
He also hopes to collaborate with UCSF colleagues on follow-up experiments to determine whether the activity of neurons lacking Dact1 is impaired in addition to the structural flaws identified in the new study and prior published work from his lab.
Meanwhile, as-yet-unpublished findings from human genetics research conducted by Cheyette’s group suggest that individuals with autism are significantly more likely than healthy comparison subjects to carry mutations in a Wnt pathway gene called WNT1.
“Just because a gene plays an important role in the embryo doesn’t mean it isn’t also important in the brain later, and might be involved in psychiatric pathology,” said Cheyette. “When these genes are mutated, someone may look fine, develop fine and have no obvious medical problems at birth, but they may also develop autism in childhood or have a psychotic break in adulthood and develop schizophrenia.”