1. Study identifies biomarker for atypical development in infants at risk for developing autism

    September 24, 2017 by Ashley

    From the Columbia University Medical Center press release:

    New research from the Sackler Institute for Developmental Psychobiology at Columbia University Medical Center (CUMC) identifies a potential biomarker that predicts atypical development in 1- to 2-month-old infants at high versus low familial risk for developing autism spectrum disorders (ASD). The search for neurobiological markers that precede atypical trajectories is important in infants with a high risk for developing autism-related disorders because early recognition allows for early intervention and mitigation of difficulties later in life.

    Using data from National Database for Autism Research (NDAR), lead author Kristina Denisova, PhD, Assistant Professor of Psychiatry at CUMC and Fellow at the Sackler Institute, studied 71 high and low risk infants who underwent two functional Magnetic Resonance imaging brain scans either at 1-2 months or at 9-10 months: one during a resting period of sleep and a second while native language was presented to the infants. After extracting measures of head movements during the scans, the statistical characteristics of these movements were quantified.

    The study found that infants at high risk for developing ASD have elevated levels of “noise” and increased randomness in their spontaneous head movements during sleep, a pattern possibly suggestive of problems with sleep. In addition, 1- to 2-month-old high risk infants showed more similar signatures while listening to native language and while sleeping while low risk infants showed distinct signatures during the two conditions.

    Further, specific features of head movements during sleep at 1-2 months predicted future flatter (delayed) early learning developmental trajectories in the high-risk babies. The existence of generally atypical learning trajectories in the high risk group was verified in separate data sets from four representative high risk infant-sibling studies comprising a total of 1,445 infants with known ASD outcomes as children. These analyses showed that high risk infants — even those without ASD diagnoses — have significantly lower functioning in childhood relative to low risk infants. The current study reveals a possible way to predict which 1-2 months-old infants will show atypical developmental trajectories as toddlers.

    Dr. Denisova said, “The finding that head movement signatures are responsive to high context stimuli (native language speech) in low but not high risk infants is informative because it suggests that infants whose siblings were diagnosed with ASD are less attuned to evolutionarily important stimuli early in life.” She added that this response pattern may underlie atypical information processing in individuals with neurodevelopmental disorders.

    Dr. Jeremy Veenstra-VanderWeele, MD, an autism researcher who was not involved in this study, noted, “This study is a good example of how existing data can be mined for new insights. Additional work is needed to replicate the current findings and understand the underlying mechanisms, but this work suggests new ways to look at movement or motor function in infants at high risk of ASD.”


  2. Origins of autism: Abnormalities in sensory processing at six months

    September 13, 2017 by Ashley

    From the McGill University press release:

    The origins of autism remain mysterious. What areas of the brain are involved, and when do the first signs appear? New findings published in Biological Psychiatry brings us closer to understanding the pathology of autism, and the point at which it begins to take shape in the human brain. Such knowledge will allow earlier interventions in the future and better outcomes for autistic children.

    Scientists used a type of magnetic resonance imaging (MRI), known as diffusion weighted imaging, to measure the brain connectivity in 260 infants at the ages of 6 and 12 months, who had either high or low risks of autism. The lengths and strengths of the connections between brain regions was used to estimate the network efficiency, a measure of how well each region is connected to other regions. A previous study with 24-month-old children found that network efficiency in autistic children was lower in regions of the brain involved in language and other behaviours related to autism. The goal of this new study was to establish how early these abnormalities occur.

    Lead author John Lewis, a researcher at the Montreal Neurological Institute and Hospital of McGill University and the Ludmer Centre for Bioinformatics and Mental Health, found network inefficiencies had already been established in six-month-old infants who went on to be diagnosed with autism. Inefficiencies in the six-month-olds appeared in the auditory cortex. He also found the extent of the inefficiency at six months of age was positively related to the severity of autistic symptoms at 24 months. As the children aged, areas involved in processing of vision and touch, as well as a larger set of areas involved in sound and language, also showed such a relation between inefficiency and symptom severity.

    Identifying the earliest signs of autism is important because it may allow for diagnosis before behavioural changes appear, leading to earlier intervention and better prospects for a positive outcome. By pinpointing the brain regions involved in processing sensory inputs as the earliest known locations of neural dysfunction related to autism, researchers narrow down the genetic factors and mechanisms that could be responsible for its development. The fact that neurological signs are already present at six months also eliminates some environmental factors as potential causes of the disorder.

    “Our goal was to discover when and where in the brain the network inefficiencies first appeared,” says Lewis. “The results indicate that there are differences in the brains of infants who go on to develop autism spectrum disorder even at six months of age, and that those early differences are found in areas involved in processing sensory inputs, not areas involved in higher cognitive functions. We hope that these findings will prove useful in understanding the causal mechanisms in autism spectrum disorder, and in developing effective interventions.”

    The research comes from the Infant Brain Imaging Study (IBIS), a collaborative effort by investigators at the Montreal Neurological Institute, and four clinical sites in the United States, coordinated to conduct a longitudinal brain imaging and behavioural study of infants at high risk for autism.


  3. Altered mitochondria associated with increased autism risk

    September 7, 2017 by Ashley

    From the Children’s Hospital of Philadelphia press release:

    Mitochondria, the tiny structures inside our cells that generate energy, may play a key role in autism spectrum disorders (ASD). A provocative new study by Children’s Hospital of Philadelphia (CHOP)’s pioneering mitochondrial medicine team suggests that variations in mitochondrial DNA (mtDNA) originating during ancient human migrations may play an important role in predisposition to ASDs.

    “Our findings show that differences in mitochondrial function are important in ASD,” said study leader Douglas C. Wallace, PhD, director of the Center for Mitochondrial and Epigenomic Medicine at CHOP. “Our team demonstrates that a person’s vulnerability to ASD varies according to their ancient mitochondrial lineage.”

    Wallace and colleagues, including Dimitra Chalkia, Larry Singh and others, published their findings in JAMA Psychiatry.

    The scientists conducted a cohort study of genetic data from 1,624 patients and 2,417 healthy parents and siblings, representing 933 families in the Autism Genetic Resource Exchange (AGRE). The Center for Applied Genomics at CHOP had previously performed genome-wide association studies on this AGRE cohort, and partnered in this study.

    Mitochondria contain their own DNA, distinct from the more familiar nuclear DNA (nDNA) inside the cell nucleus. The mtDNA codes for essential genes governing cellular energy production, and those genes exchange biological signals with nDNA to affect our physiology and overall health.

    The current study analyzed single-nucleotide functional variants — base changes in the cohort’s mtDNA that characterize mitochondrial haplogroups. Haplogroups are lineages of associated mtDNA variants that reflect the ancient migration patterns of early human bands that spread out of Africa to the rest of the world during prehistory. Based on his seminal 1980 discovery that the human mtDNA is inherited only through the mother, Wallace’s surveys over the years, covering mtDNA variation among indigenous populations around the world, have permitted the reconstruction of human worldwide migrations and evolution patterns over hundreds of millennia.

    The current study found that individuals with European haplogroups designated I, J, K, X, T and U (representing 55 percent of the total European population) had significantly higher risks of ASD compared to the most common European haplogroup, HHV. Asian and Native American haplogroups A and M also were at increased risk of ASD.

    These mitochondrial haplogroups originated in different global geographic areas, adapted through evolution to specific regional environments. However, subsequent changes, such as migration, changes in diet, and other environmental influences, can create a mismatch between the physiology of a particular mtDNA lineage and the individual’s environment, resulting in predisposition to disease. Additional nDNA genetic factors or environmental insults may further reduce an individual’s energy output until it is insufficient to sustain normal brain development and function, resulting in disease.

    As the wiring diagram for cellular power plants, mtDNA is crucial in supplying energy to the body. The brain is particularly vulnerable to even mild energy deficiencies because of its high mitochondrial energy demand. Wallace’s previous studies have shown that mitochondrial dysfunction can disturb the delicate balance between inhibition and excitation in brain activity — a crucial factor in ASDs and other neuropsychiatric disorders. “There may be a bioenergetic threshold,” says Wallace, adding that an individual already predisposed to ASD based on their mitochondrial haplogroup may be pushed below that threshold by the chance occurrence of additional genetic variants or environmental insults.

    The striking tendency for ASD to occur more frequently in males than females may reflect another peculiarity of mitochondrial genetics, added Wallace. Males are four times more likely to suffer blindness from a well-known mtDNA disease, Leber hereditary optic neuropathy (LHON). The lower risk of blindness in females may arise from estrogen effects in mitochondria that increase beneficial antioxidant activity.

    Wallace said that his team’s finding that subtle changes in mitochondrial energetics are important risk factors in ASD suggests potential alternative approaches for therapy. He added, “There is increasing interest in developing metabolic treatments for known mtDNA diseases such as LHON. If ASD has a similar etiology, then these same therapeutic approaches may prove beneficial for ASD.”


  4. People with autism spectrum disorder show neural responses of anxiety on seeing social touch

    September 5, 2017 by Ashley

    From the University of Haifa press release:

    People with strong signs of autism spectrum disorder (ASD) show neural signs of anxiety when they see social touch and report unpleasant feelings about social touch by comparison to people with weak signs of ASD. This finding has emerged from a new study undertaken at the University of Haifa. “Until now, it was clear that many people with ASD dislike touch. This study enables us to understand that they actually experience touch in a similar way to anxiety,” explains Leehe Peled-Avron, a doctorate student in the Department of Psychology, who undertook the study.

    The autism spectrum is a developmental disorder characterized by difficulties in creating, understanding, and maintaining social relationships. Some 70-80 percent of people with ASD suffer from hypersensitivity or undersensitivity to neural stimulation through the various senses, including sight, touch, and taste. Some parents of children with ASD report that their children stiffen when touched, try to avoid touch, and prefer to be touched on their own terms. Until now, however, researchers did not understand exactly what causes this sensitivity, and above all — how people with ASD feel when they are exposed to touch.

    The present study, published in the journal Autism Research, was authored by Prof. Simone Shamay-Tsoory and doctorate student Leehe Peled-Avron from the Department of Psychology at the University of Haifa. The researchers sought to examine the differences in the neural response to social interaction, including human touch, between people with ASD and people without the disorder.

    Fifty-four participants were divided into two groups: one group of people with ASD who have a high level of social functioning, and one group without signs of ASD. The participants were shown 260 pictures in four categories: social touch between two people photographed in natural conditions, such as malls, parties, social events, and so forth; social interaction between the same people without touch; two everyday inanimate objects touching; and two inanimate objects not touching.

    The results of the study show that people with ASD reported unpleasant sensations when they watched social touch, compared to people without ASD. The examination of their brain waves showed that when they watched social interaction including touch, the neural signals in their brain were ones that we recognize as signals of someone in a state of anxiety. It was also found that these neural signals of anxiety increase the stronger the patterns of ASD. In other words, the higher a person is diagnosed on the autistic spectrum, the stronger their neural signals, possibly reflecting a greater level of anxiety at social touch. When the participants watched the same social interactions without touch, these signals were not present, showing that it was the element of touch that created the anxiety, and not the social interaction. “Similar neural signals to those we found have been reported in studies on phobias. If someone suffers from a specific trauma and we show them the traumatic object, the neural signals that result are identical to those we found in the study,” Peled-Avron explains.

    “The results of this study improve our understanding of people diagnosed with ASD. Social touch is an integral part of our lives, in both happy and sad events, and now we can understand why for some people on the autistic spectrum all these events arouse anxiety. As well as understanding them, this insight may be very helpful for therapists, who can offer therapy focusing on anxiety in a similar manner to therapy for phobias, whether by means of psychotherapy or medication,” the researchers concluded.


  5. Study suggests people with autism are less surprised by the unexpected

    August 16, 2017 by Ashley

    From the University College London press release:

    Adults with autism may overestimate the volatility of the world around them, finds a new UCL study published in Nature Neuroscience.

    The researchers found that adults with autism were less surprised by unexpected images in a simple learning task than adults without autism, and those who were the least surprised had the most pronounced symptoms.

    “We know from previous studies that people with autism often aren’t surprised by things that would surprise other people,” said lead author Dr Rebecca Lawson (UCL Wellcome Trust Centre for Neuroimaging). “Our results suggest that this may be because of differences in how people with autism build expectations. Our expectations bias our behaviour in subtle ways, so being less susceptible to these effects may result in strengths as well as difficulties.”

    Insistence on sameness and intolerance of change are part of the diagnostic criteria for autism, but there has been little research addressing how people with autism represent and respond to unexpected changes to their environment.

    In this study, 24 adults with autism and 25 adults without autism completed a task that involved learning to expect to see different pictures on a computer screen after hearing either a high or low sound.

    The researchers applied computational modelling to the data to characterize each person’s learning process. They found that adults with autism tend to overestimate how changeable the environment is, which reduces how much their prior expectations guide their behaviour.

    The adults with autism learned the task well enough overall, but showed differences in updating their expectations when the environment unexpectedly became more volatile.

    “When we’re uncertain about our own beliefs, such as under volatile conditions, we’re driven more by our senses than our prior expectations. If people with autism are more often expecting volatility, that could help explain their propensity to sensory overload, enhanced perceptual functioning and context insensitivity,” said Dr Lawson.

    The study found that the ability to form expectations about upcoming pictures was related to the severity of communication problems in people with autism. Senior author Professor Geraint Rees (UCL Wellcome Trust Centre for Neuroimaging) said: “The idea that differences in how people with autism build visual expectations may link to social difficulties is an intriguing possibility, and one that we would like to pursue further in consultation with members of the autism community.”

    The computational measures of learning and surprise were also linked to changes in pupil size, which is believed to reflect the function of brain chemicals called neuromodulators, such as noradrenaline.

    “This work opens up the possibility of using computational modelling with more direct measures of brain function to help us understand the neural basis of differences in how we learn about changes in the environment,” said co-author Dr Christoph Mathys (SISSA — Trieste, Italy).

    Dr Lawson added: “The individual differences in how people represent and respond to the world are often more striking than the similarities. This research represents an important advance in our understanding of how people with autism see the world differently.”


  6. Autism severity detected with brain activity test

    August 11, 2017 by Ashley

    From the University of California – Los Angeles press release:

    UCLA researchers have discovered that children with autism have a tell-tale difference on brain tests compared with other children. Specifically, the researchers found that the lower a child’s peak alpha frequency — a number reflecting the frequency of certain brain waves — the lower their non-verbal IQ was. This is the first study to highlight peak alpha frequency as a promising biomarker to not only differentiate children with autism from typically developing children, but also to detect the variability in cognitive function among children with autism.

    Autism spectrum disorder affects an estimated one in 68 children in the United States, causing a wide range of symptoms. While some individuals with the disorder have average or above-average reasoning, memory, attention and language skills, others have intellectual disabilities. Researchers have worked to understand the root of these cognitive differences in the brain and why autism spectrum disorder symptoms are so diverse.

    An electroencephalogram, or EEG, is a test that detects electrical activity in a person’s brain using small electrodes that are placed on the scalp. It measures different aspects of brain activity including peak alpha frequency, which can be detected using a single electrode in as little as 40 seconds and has previously been linked to cognition in healthy individuals.

    The researchers performed EEGs on 97 children ages 2 to 11; 59 had diagnoses of autism spectrum disorder and 38 did not have the disorder. The EEGs were taken while the children were awake and relaxed in dark, quiet rooms. Correlations among age, verbal IQ, non-verbal IQ and peak alpha frequency were then studied.

    The discovery that peak alpha frequency relates directly to non-verbal IQ in children with the disorder suggests a link between the brain’s functioning and the severity of the condition. Moreover, it means that researchers may be able to use the test as a biomarker in the future, to help study whether an autism treatment is effective in restoring peak alpha frequency to normal levels, for instance.

    More work is needed to understand whether peak alpha frequency can be used to predict the development of autism spectrum disorder in young children before symptoms emerge.

    The study was published online in the European Journal of Neuroscience.


  7. Researchers develop set of guidelines for art therapy for children with ASD

    August 9, 2017 by Ashley

    From the Florida State University press release:

    A Florida State University researcher is working with art therapists to find better ways to treat children who have Autism Spectrum Disorder (ASD).

    Theresa Van Lith, assistant professor of art therapy in FSU’s Department of Art Education, led a study that surveyed art therapists working with children with ASD to develop a clearer understanding of their techniques and approaches. The study was published this month in the journal Arts in Psychotherapy.

    “I had noticed that is there is a high number of art therapists working with people who have autism, but I wanted to understand what their practice wisdoms were in terms of how they go about facilitating art therapy sessions,” Van Lith said. “We want to make it a transparent process for the client or the parents of a client, so they know what to expect.”

    The Center for Disease Control and Prevention estimates that one in 68 children is diagnosed with Autism Spectrum Disorder by age 8 each year. As that population grows, more parents and educators are seeking out art therapists to address social development and sensory issues that generally accompany ASD.

    The research team compiled and analyzed the art therapists’ expert opinions on topics such as what worked with ASD clients, their objectives during a session, their most preferred theoretical approach and the considerations they had to make when working with children with ASD.

    “We realized there wasn’t a consensus with the theoretical approaches they used,” Van Lith said. “They were having to use a number of theoretical approaches together, and we wanted to understand what that would be like in practice.”

    While the survey results varied, the researchers were able to develop a set of guidelines for delivering art therapy to children who have ASD. The proposed guidelines will serve as a basis of successful practice for new art therapy professionals and for further studies.

    “We used these practice wisdoms from art therapists around the field to understand the most effective and beneficial way to use art therapy with child with ASD,” Van Lith said.

    Some of the best practices found were: use the same routine to begin each session, explain instructions in a consistent manner, spark curiosity to teach new skills and be aware of transitions between activities.

    The researchers also outlined aspects of practice that were found not to be useful. They warned art therapists on a handful of factors that could have adverse effects on clients such as being overly directive or too loose with direction, using over stimulating art materials and forcing or being restrictive with communication styles.

    “That’s important because sometimes there is the assumption of ‘why can’t anyone do these techniques?'” Van Lith said. “People wonder why art therapy can’t be conducted in a much less formal situation. However, they don’t realize there are nuances in the way we deliver the art therapy directive — a lot of that is about knowing the client and the way a client responds to communication.”

    Based on these guidelines and consensus, Van Lith is rolling out a larger study to demonstrate the efficacy of that working model.

    “The idea is that, over time, we can build up the evidence that art therapy is effective for these children, and we can demonstrate how and why that is the case,” Van Lith said.

    The ultimate goal is to educate art therapists about best practices as well as inform clients, parents and teachers about possible benefits of art therapy for children with ASD.

    “As a result of more transparency, the clients can appreciate or understand some of the changes that might be going on for them as they receive art therapy,” Van Lith said. “We don’t want it to be a mysterious process.”

    Van Lith co-authored the study with Jessica Stallings, associate professor at Emporia State University, and FSU alumna Chelsea Harris, who practices at the Emory Autism Center.


  8. Adults with autism make more consistent choices

    July 17, 2017 by Ashley

    From the Association for Psychological Science press release:

    People with autism spectrum conditions (ASC) often show a reduced sensitivity to contextual information in perceptual tasks, but new research suggests that this reduced sensitivity may actually lead to more consistent choices in high-level decision-making tasks.

    The findings, published in Psychological Science, a journal of the Association for Psychological Science, indicate that individuals with ASC are less susceptible to the effects of decoy options when evaluating and choosing the “best” product among several options relative to individuals without ASC.

    “People with autism are indeed more consistent in their choices than the neurotypical population. From an economic perspective, this suggests that people with autism are more rational and less likely to be influenced by the way choices are presented,” says psychology researcher George Farmer of the University of Cambridge.

    While numerous studies have compared the performance of individuals with ASC and neurotypical individuals on a variety of low-level perceptual tasks, Farmer and University of Cambridge co-authors William J. Skylark and Simon Baron-Cohen noticed that relatively little research had examined their performance in the realm of decision making.

    People with autism are thought to focus more on detail and less on the bigger picture — this is often found in more perceptual studies, for instance by showing that people with autism are less susceptible to some visual illusions,” explains Farmer. “We wanted to know if this tendency would apply to higher-level decision-making tasks.”

    The researchers recruited 90 adults with ASC and 212 neurotypical adults to participate in an online decision-making study. The researchers used 10 product pairs and the products in each pair differed on two dimensions. Importantly, the pairs were always presented as part of a trio that included a third decoy item.

    Participants saw each pair twice — in one case, the accompanying decoy was designed to target product A; in the other case, it was designed to target product B. The participants indicated the “best” option out of the three presented.

    For example, participants might be asked to choose one of three USB drives that varied according to their capacity and their lifespan. Product A has a capacity of 32 GB and a lifespan of 20 months, while Product B has less capacity (16 GB) but a longer lifespan (36 months). The decoy, with a capacity of 28 GB and lifespan of 16 months, is objectively worse than A and should therefore be ignored.

    Participants also completed measures assessing aspects of cognitive ability and a measure that assessed traits typically associated with ASC.

    With purely rational economic decision making, the decoy items would be irrelevant and participants would make the same choice both times that products A and B were shown. If the decoys were effective, however, participants would switch their selection when the decoy changed, favoring the product targeted by the decoy in each trio. In the example above, people would be more likely to choose Product A with the decoy present than they would if there were simply comparing Product A and B.

    The data revealed that, compared with neurotypical participants, participants with ASC made more consistent choices and made fewer switches in their selections.

    In a second experiment, the researchers recruited participants from the general population, administering the same task with only those who scored in the bottom and top deciles of a validated measure of traits typically associated with autism. Their results showed an attenuated pattern similar to that seen in the first experiment: Participants who scored high on autistic traits were more likely to make consistent choices compared with low-scoring participants.

    Together, the findings indicate that individuals with ASC are less likely to show a cognitive bias that often affects their neurotypical peers.

    “[C]hoice consistency is regarded as normative in conventional economic theory, so reduced context sensitivity would provide a new demonstration that autism is not in all respects a ‘disability’,” the researchers write in their paper.

    “These findings suggest that people with autism might be less susceptible to having their choices biased by the way information is presented to them — for instance, via marketing tricks when choosing between consumer products,” Farmer adds.

    The results also indicate that the reduced sensitivity to context that is associated with ASC may extend well beyond low-level cognitive processes, shedding new light on the nature of “autistic cognition,” the researchers argue:

    “Altered preferences in a choice task involving verbally described consumer products would suggest the need for a broader characterization and integrated theorizing across levels and domains of processing,” they conclude.


  9. Possible early diagnosis of autism spectrum disorder

    July 16, 2017 by Ashley

    From the UT Southwestern Medical Center press release:

    Measuring a set of proteins in the blood may enable earlier diagnosis of autism spectrum disorder (ASD), according to a study from the Peter O’Donnell Jr. Brain Institute at UT Southwestern Medical Center.

    The research found that the levels of two proteins previously identified as potential markers for ASD could help scientists accurately diagnose the disorder in approximately 75 percent of the children studied. When the two proteins are measured together, the diagnostic accuracy increased to 82 percent.

    The study published in the Journal of Neuroinflammation is among several recent and ongoing efforts to improve early diagnosis of ASD by shifting focus to biological measurements instead of behavioral symptoms.

    Progress in this area could lead to earlier intervention and help limit the effects of the disorder, said Dr. Dwight German, study senior author and Professor of Psychiatry at UT Southwestern.

    “ASD is a very heterogeneous disorder, and if we can identify biomarkers for even a subgroup of ASD patients, then that would be extremely helpful not only for early diagnosis but also for the development of therapeutics,” said Dr. German, whose latest research builds upon an ASD finding published last year in Scientific Reports.

    ASD affects approximately 1 in 68 children in the U.S. The neurodevelopmental disorder is characterized by social interaction and communication challenges, and restricted and repetitive patterns of behavior.

    Most cases are not diagnosed until about age 4, when communication and social disabilities become apparent. However, recent research offers hope that detection may be possible by age 1 by measuring brain growth.


  10. Mice provide insight into genetics of autism spectrum disorders

    July 15, 2017 by Ashley

    From the University of California – Davis press release:

    While the definitive causes remain unclear, several genetic and environmental factors increase the likelihood of autism spectrum disorder, or ASD, a group of conditions covering a “spectrum” of symptoms, skills and levels of disability.

    Taking advantage of advances in genetic technologies, researchers led by Alex Nord, assistant professor of neurobiology, physiology and behavior with the Center for Neuroscience at the University of California, Davis, are gaining a better understanding of the role played by a specific gene involved in autism. The collaborative work appears June 26 in the journal Nature Neuroscience.

    “For years, the targets of drug discovery and treatment have been based on an unknown black box of what’s happening in the brain,” said Nord. “Now, using genetic approaches to study the impact of specific mutations found in cases, we’re trying to build a cohesive model that links genetic control of brain development with behavior and brain function.”

    The Nord laboratory studies how the genome encodes brain development and function, with a particular interest in understanding the genetic basis of neurological disorders.

    Mouse brain models

    There is no known specific genetic cause for most cases of autism, but many different genes have been linked to the disorder. In rare, specific cases of people with ASD, one copy of a gene called CHD8 is mutated and loses function. The CHD8 gene encodes a protein responsible for packaging DNA in cells throughout the body. Packaging of DNA controls how genes are turned on and off in cells during development.

    Because mice and humans share on average 85 percent of similarly coded genes, mice can be used as a model to study how genetic mutations impact brain development. Changes in mouse DNA mimic changes in human DNA and vice-versa. In addition, mice exhibit behaviors that can be used as models for exploring human behavior.

    Nord’s laboratory at UC Davis and his collaborators have been working to characterize changes in brain development and behavior of mice carrying a mutated copy of CHD8.

    “Behavioral tests with mice give us information about sociability, anxiety and cognition. From there, we can examine changes at the anatomical and cellular level to find links across dimensions,” said Nord. “This is critical to understanding the biology of disorders like autism.”

    By inducing mutation of the CHD8 gene in mice and studying their brain development, Nord and his team have established that the mice experience cognitive impairment and have increased brain volume. Both conditions are also present in individuals with a mutated CHD8 gene.

    New implications for early and lifelong brain development

    Analysis of data from mouse brains reveals that CHD8 gene expression peaks during the early stages of brain development. Mutations in CHD8 lead to excessive production of dividing cells in the brain, as well as megalencephaly, an enlarged brain condition common in individuals with ASD. These findings suggest the developmental causes of increased brain size.

    More surprisingly, Nord also discovered that the pathological changes in gene expression in the brains of mice with a mutated CHD8 continued through the lifetime of the mice. Genes involved in critical biological processes like synapse function were impacted by the CHD8 mutation. This suggests that CHD8 plays a role in brain function throughout life and may affect more than early brain development in autistic individuals.

    While Nord’s research centers on severe ASD conditions, the lessons learned may eventually help explain many cases along the autism spectrum.

    Collaborating to improve understanding

    Nord’s work bridges disciplines and has incorporated diverse collaborators. The genetic mouse model was developed at Lawrence Berkeley National Laboratory using CRISPR editing technology, and co-authors Jacqueline Crawley and Jill Silverman of the UC Davis MIND Institute evaluated mouse behavior to characterize social interactions and cognitive impairments.

    Nord also partnered with co-author Konstantinos Zarbalis of the Institute for Pediatric Regenerative Medicine at UC Davis to examine changes in cell proliferation in the brains of mice with the CHD8 mutation, and with Jason Lerch from the Mouse Imaging Centre at the Hospital for Sick Children in Toronto, Canada, to conduct magnetic resonance imaging on mouse brains.

    “It’s the act of collaboration that I find really satisfying,” Nord said. “The science gets a lot more interesting and powerful when we combine different approaches. Together we were able to show that mutation to CHD8 causes changes to brain development, which in turn alters brain anatomy, function and behavior.”

    In the future, Nord hopes to identify how CHD8 packages DNA in neural cells and to determine the specific impacts to early brain development and synaptic function. Nord hopes that deep exploration of CHD8 mutations will ultimately yield greater knowledge of the general factors contributing to ASD and intellectual disability.