1. Study suggests girls’ social camouflage skills may delay or prevent autism diagnosis

    January 17, 2018 by Ashley

    From the Children’s National Health System press release:

    On parent-reporting measures, girls with autism seem to struggle more than boys with performing routine tasks like getting up and dressed or making small talk, even when the study group is normalized to meet similar basic clinical diagnostic criteria across sexes. The findings add to the growing evidence that girls with autism may show symptoms differently than boys, and that some of the social difficulties experienced by females with autism may be masked during clinical assessments.

    The new study, led by researchers from the Center for Autism Spectrum Disorders at Children’s National Health System, was published in the Journal of Autism and Developmental Disorders.

    “Based on our research criteria, parents report that the girls in our study with autism seem to have a more difficult time with day-to-day skills than the boys,” says Allison Ratto, Ph.D., lead author of the study and a clinical psychologist within the Center for Autism Spectrum Disorders at Children’s National. “This could mean that girls who meet the same clinical criteria as boys actually are more severely affected by ongoing social and adaptive skill deficits that we don’t capture in current clinical measures, and that autistic girls, in general, may be camouflaging these types of autism deficits during direct assessments.”

    The study used an age-and IQ-matched sample of school-aged youth diagnosed with ASD to assess sex differences according to the standard clinical tests including the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R), as well as parent reported autistic traits and adaptive skills.

    “This study is one of the first to eliminate many of the variables that obscure how sex impacts presentation of autism traits and symptoms. Though today’s clinical tools do a really good job capturing boys at a young age, with a wide range of symptom severity, they do it less effectively for girls,” adds Lauren Kenworthy, Ph.D., director of the Center for Autism Spectrum Disorders, and another study contributor. “This is a crucial issue considering how much we know about the success of early interventions on long-term outcomes. We have to find better ways to identify girls with autism so we can ensure the best approaches reach all who need them as early as possible.”

    Specific evidence of women more effectively masking or camouflaging social and communication deficits is limited, but autistic self-advocates theorize that the unique social pressures and demands on girls at a young age may teach them to “blend in” and “get by,” including maintaining successful, brief social interactions.

    As a research partner of an $11.7 million Autism Center of Excellence (ACE) grant from the National Institutes of Health to the George Washington University Autism and Neurodevelopment Disorders Institute, the Center for Autism Spectrum Disorders at Children’s National will continue investigations into sex differences, and aims to develop self-reporting measures for adolescents and adults that better capture additional populations — including females and non-cisgender males.

    “We hope the ACE studies will help us better understand the diversity of the autism spectrum by allowing us to focus on the ways in which differences in sex and gender identity might influence the expression of autistic traits, thereby enabling us to make more accurate diagnoses,” Dr. Ratto concludes.


  2. Gene expression study may provide insights into autism, other neurodevelopmental disorders

    December 18, 2017 by Ashley

    From the University of California – San Francisco press release:

    The human brain has been called the most complex object in the cosmos, with 86 billion intricately interconnected neurons and an equivalent number of supportive glial cells. One of science’s greatest mysteries is how an organ of such staggering complexity — capable of producing both love poetry and scientific discovery — builds itself from just a handful of stem cells in the early embryo.

    Now researchers at UC San Francisco have taken the first step towards a comprehensive atlas of gene expression in cells across the developing human brain, making available new insights into how specific cells and gene networks contribute to building this most complex of organs, and serving as a resource for researchers around the world to study the interplay between these genetic programs and neurodevelopmental disorders such as autism, intellectual disability, and schizophrenia.

    The work described in the new paper — published December 8, 2017, in Science — was led by three young UCSF researchers: Tomasz Nowakowski, PhD, an assistant professor of anatomy; Alex Pollen, PhD, an assistant professor of neurology; and Aparna Bhaduri, PhD, when all three were post-doctoral researchers in the UCSF lab of Arnold Kriegstein, MD, PhD, the new paper’s senior author.

    “It’s critically important to be able to look at questions of brain development in real human tissue when you’re trying to study human disease. Many of the insights we’re able to gain with this data can’t be seen in the mouse,” said Kriegstein, a professor of neurology and director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF.

    Previously, Pollen and Nowakowski had developed techniques for analyzing distinctive patterns of DNA activity in individual cells extracted from human brain tissue. The approach enabled a wide range of studies of human brain development, including implicating a new class of neural stem cell recently discovered by the lab in the evolutionary expansion of the human brain and identifying how the mosquito-borne Zika virus may contribute to microcephaly in infants infected in utero.

    Working with Bhaduri, who has a background in statistics and bioinformatics, Pollen and Nowakowski began exploring how specific classes of neurons and stem cells in the developing brain contribute to normal brain growth as well as to neurodevelopmental disease, and have begun to build a comprehensive, open-source atlas of gene expression across the developing brain, which they hope will serve as a resource for other scientists.

    “This is an attempt to generate an unbiased view of what genes are expressed in every cell type in the developing human brain in order to highlight potential cellular vulnerabilities in patient-relevant mutations,” said Nowakowski.

    “Identifying gene variants that are general risk factors for neurological and psychiatric disease is important, but understanding exactly which cell types in the developing brain are compromised and what the consequences are is still extremely challenging,” Pollen added. “A cell atlas could serve as a bridge to help us to do this with more confidence.”

    In their new Science paper, the researchers analyzed gene expression in single cells across key developmental time points and from different regions of the brain. Bhaduri then used statistical algorithms to cluster different cells based on their patterns of gene expression.

    This analysis allowed the team to trace the genetic signals driving brain development at a much finer level, both regionally and over time, than had previously been possible. For example, the researchers were able to identify previously unknown gene expression differences between the neural stem cells that give rise to the brain’s deep structures versus its neocortical surface, and to show that molecular signatures of different neural cell types arise much earlier in brain development than previously realized.

    “I was excited to come into this project with an incredibly rich dataset to analyze,” Bhaduri said. “By analyzing this dataset in new ways, we were able to discover early molecular distinctions across areas and over time that begin to specify the astonishing diversity of neurons in the cerebral cortex.”

    One of the team’s most exciting new observations suggests a link between autism and a type of neural stem cell called outer-radial glia (oRGs), discovered by the Kriegstein lab in 2010. These stem cell populations are greatly expanded in primates and may be responsible for the radical expansion of the cortex that gave rise to human intelligence. In the new study, the researchers discovered that during the second trimester of human brain development, oRG cells express genes related to a fundamental signaling pathway called mTOR, defects in which have previously been implicated in autism and several other psychiatric disorders. This finding suggests that future studies should also consider the role mTOR-expressing oRG cells may play in the origins of these disorders.

    Another provocative observation from the new study was that transient gene expression events during brain development set up broad distinctions in neural fate between cells in different areas in the cerebral cortex. This contrasts with an idea that has been dominant in neuroscience for many years: that the neocortex is made up of nearly identical “cortical columns” — a standard circuit of distinct cell types that connect across the cortex’s six layers — which tile the cortical surface like the hexagons in a honeycomb. In that model, the cell types and their local connections are generally similar everywhere — it’s just the inputs and outputs to the column that vary from place to place in the cortex. In contrast, the new data suggest that neurons in different parts of the brain express fundamentally different genetic programs during development, while nearby neurons in different layers of the cortex are surprisingly similar in their gene expression.

    The authors say the new paper is the first step in a larger effort to build a comprehensive atlas of genetically-defined cell types in the human brain. Kriegstein’s team recently received a 5-year $5 million grant from the National Institutes of Health (NIH) BRAIN Initiative to expand this effort, and to make the resulting data available publicly to all in the field through an interactive data browser built in collaboration with colleagues at UC Santa Cruz.

    “This study focused on the development of the neocortex, but we aim to analyze multiple brain regions and developmental stages to achieve a more comprehensive atlas of cell types in the developing human brain,” Kriegstein said. “It’s still a fundamentally open question how many cell types there are in the brain, which clearly has more cellular diversity than any other organ.”

    “We hope this atlas will be a roadmap for the field to explore the relationship between specific cell types, signaling pathways, receptors, and the physiological function of brain circuits,” Kriegstein added. “For example, there is a huge amount of interest and excitement globally in growing cerebral organoids” — miniature brain-like organs that can be studied in laboratory experiments — “from stem cells to model human brain development and disease mechanisms. Our brain development atlas will serve as a much-needed framework to calibrate these organoids against the real human brain.”


  3. Study examines brain activity and anxiety symptoms in youth with autism spectrum disorder

    December 14, 2017 by Ashley

    From the Wiley press release:

    The error-related negativity (ERN) is a brain signal response to errors that is thought to reflect threat sensitivity and has been implicated in anxiety disorders in individuals without autism spectrum disorder (ASD). A new Autism Research study has revealed that the ERN is related to social anxiety symptoms — specifically performance fears — in youth with ASD.

    The findings suggest that heightened threat sensitivity may be characteristic of people with ASD who exhibit social fearfulness. Those with more severe ASD symptoms and/or lower verbal abilities may have difficulty identifying or communicating their performance anxieties. Therefore, the ERN may provide important and perhaps otherwise inaccessible information on how these individuals experience internal sources of threat.

    “This study, led by my graduate student, Tamara Rosen, clarifies and focuses inconsistencies in previous research on the unique way error processing manifests and can impact anxiety symptoms in individuals with ASD,” said senior author Dr. Matthew Lerner, of Stony Brook University. “These findings can help guide and pinpoint efforts to diagnose and treat the substantial co-occurring anxiety experienced by many people with ASD.”


  4. Mothers of teens with autism report higher levels of stress, but optimism can be a buffer

    December 7, 2017 by Ashley

    From the University of California – Riverside press release:

    Anyone who has ever survived being a teenager should be well aware that parenting a teenager can be no easy feat. But factor in a diagnosis of autism spectrum disorder (ASD) or intellectual disability (ID), and you’ll likely have the recipe for a unique set of challenges to the entire family unit.

    According to autism expert Jan Blacher, a distinguished professor in the Graduate School of Education at the University of California, Riverside, the effects of those challenges went largely understudied for years while medical professionals blamed mothers of children diagnosed with ASD for their kids’ disorders.

    Beginning in the 1950s, doctors turned to psychiatrist Leo Kanner’s “refrigerator mother” theory as evidence that a lack of maternal warmth could essentially cause autism. It wasn’t until the mid-1960s when psychologist Bernard Rimland, among others, began to discredit Kanner’s theory, instead popularizing the idea that autism could be rooted in neurological development, or even genetics.

    Decades later, the race to find autism-linked genes continues. But it doesn’t yet benefit families of kids with ASD, said Blacher and her research colleague, UCLA’s Bruce L. Baker.

    Within those families, the impacts of raising children with autism hit mothers especially hard, resulting in what Blacher and Baker refer to as “collateral effects.”

    In a study recently published online in the Journal of Autism and Developmental Disorders, the researchers found that mothers of teenagers with ASD or ID reported higher levels of stress and other negative psychological symptoms — think depression or anxiety — than mothers of teenagers with typical development, or TD.

    Those levels climbed even higher when teenagers with ASD or ID also showed signs of clinical-level disruptive behavior disorders.

    To find out how such disorders affected mothers, Blacher and Baker surveyed 160 13-year-olds and their families. Eighty-four of the study’s teenage participants were classified as having typical development, or TD; 48 as having ASD; and 28 as having ID.

    As the director of UCR’s SEARCH (Support, Education, Advocacy, Resources, Community, and Hope) Family Autism Resource Center, Blacher works with kids of all ages with ASD. She said this study, however, is special because it focuses on a pool of adolescents who are the same age.

    “Usually when studies have looked at the impacts of autism on families, the children involved have reflected wide ranges of ages,” she said. “Here, we’ve eliminated the variance related to developmental stage.”

    Blacher and Baker first assessed mothers and their 13-year-olds during in-person visits at their research site, and later asked mothers to complete separate questionnaires privately to measure youth behavior problems and parental well-being.

    “ASD group mothers scored highest on each of the two distress indicators,” the researchers wrote, adding that ASD group mothers’ levels of stress and psychological symptoms did not differ significantly from those of ID group mothers.

    The findings harken back to research demonstrating that parents of children with ASD have reported levels of stress consistent with those of individuals who experience post-traumatic stress disorder.

    What’s more, mothers’ levels of parenting-related stress and other psychological symptoms were amplified by the presence of one or more clinical-level behavior disorders, Blacher and Baker said.

    “The most common disruptive behavior disorder is attention deficit hyperactivity disorder, or ADHD, but children with autism can also show signs of oppositional defiant disorder, depression, and anxiety,” Blacher said. “The disorders that are most disruptive to parents are those we describe as ‘acting out’ disorders and involve behaviors like not following rules, hitting, screaming, arguing, lashing out, and breaking things.”

    Still, the researchers emphasized that parents who face childrearing challenges need not resign themselves to lifetimes of mounting stress. The mothers they studied who demonstrated more resilience had one thing in common: an optimistic outlook on life.

    Using the Life Orientation Test, which assesses individuals’ optimism or pessimism, Blacher and Baker found that mothers who were more optimistic — believing that good rather than bad things would happen to them — experienced fewer negative impacts associated with parenting a child with ASD or ID and comorbid behavior disorders.

    In those cases, a more positive outlook on life became a buffer against parenting-related stressors.

    “It’s in the face of stress when optimism really becomes important,” Blacher said. “A mom that has a high level of optimism is going to be able to better weather stress and be better prepared mentally for the challenges ahead.”


  5. Researchers develop video game that improves balance in youth with autism

    December 2, 2017 by Ashley

    From the University of Wisconsin-Madison press release:

    Playing a video game that rewards participants for holding various “ninja” poses could help children and youth with autism spectrum disorder (ASD) improve their balance, according to a recent study in the Journal of Autism and Developmental Disorders led by researchers at the University of Wisconsin-Madison.

    Balance challenges are more common among people with ASD compared to the broader population, says study lead author Brittany Travers, and difficulties with balance and postural stability are commonly thought to relate to more severe ASD symptoms and impaired activities in daily living.

    “We think this video game-based training could be a unique way to help individuals with ASD who have challenges with their balance address these issues,” says Travers, an investigator at UW-Madison’s Waisman Center and an assistant professor of kinesiology.

    In this pilot study — the largest ever to look at the effects of balance training on individuals with ASD — 29 participants between the ages of 7 and 17 with ASD completed a six-week training program playing a video game developed by the researchers.

    By the end of the program, study participants showed significant improvements in not only their in-game poses but also their balance and posture outside of the game environment.

    According to Travers, balance improvements outside the video game context are especially important. “Our participants are incredibly clever when it comes to finding ways to beat video games!” she says. “We wanted to make sure that the improvements we were seeing were truly balance-related and not limited to the video game.”

    Ten out of 11 study participants who completed a post-game questionnaire also said they enjoyed playing the video games.

    “We always aim to make the interventions fun,” says Travers. “We have couched a rigorous exercise (by the end of some gaming sessions, participants had been standing on one foot for 30 minutes) in a video game format, so we were delighted to hear that the participants enjoyed the game.”

    Travers developed the video game with help from Andrea Mason, professor of kinesiology at UW-Madison, Leigh Ann Mrotek, professor of kinesiology at UW-Oshkosh and Anthony Ellertson, program director of gaming and interactive technology at Boise State University.

    The gaming system uses a Microsoft Kinect camera and a Nintendo Wii balance board connected to software developed on a Windows platform using Adobe Air.

    “Players see themselves on the screen doing different ‘ninja’ poses and postures, and they are rewarded for doing those poses and postures; that’s how they advance in the game,” says Travers.

    The study also explored individual differences that might predict who would benefit most from this type of video game-based balance training.

    For example, the study showed that participants with some characteristics, such as ritualistic behaviors (like the need to follow a set routine around mealtimes or bedtime) did not benefit as much from the video game as those without these behaviors.

    On the other hand, some characteristics, such as body mass index or IQ, did not influence whether a participant benefited from balance training.

    “There is a lot of variability in the clinical profile of ASD, and it’s unlikely that there will be a one-size-fits-all approach for balance training that helps all individuals with ASD,” says Travers.

    Researchers are working to make the game more accessible to different individuals within the autism spectrum. “We already have some features that help — the game has very little verbal instruction, which should make it more accessible to individuals who are minimally verbal,” says Travers. “Ultimately, we would like to move this video game-based training outside the lab.”


  6. Study suggests school exacerbates feelings of being ‘different’ in pupils with Autism Spectrum Conditions

    November 28, 2017 by Ashley

    From the University of Surrey press release:

    autism_stairsNegative school experiences can have harmful long term effects on pupils with Autism Spectrum Conditions, a new study in the journal Autism reports.

    Researchers from the University of Surrey have discovered that experiences of social and emotional exclusion in mainstream schools can adversely affect how pupils with autism view themselves, increasing their risk of developing low self-esteem, a poor sense of self-worth and mental health problems.

    Examining 17 previous studies in the area, researchers discovered that how pupils with autism view themselves is closely linked to their perceptions of how other’s treat and interact with them. They found that a tendency of many pupils with the condition to internalise the negative attitudes and reactions of others toward them, combined with unfavourable social comparisons to classmates, leads to a sense of being ‘different’ and more limited than peers.

    Negative self-perception can lead to increased isolation and low self-esteem making pupils with autism more susceptible to mental health problems.

    It was discovered that the physical environment of schools can impact on children’s ability to interact with other pupils. Sensory sensitivity, which is a common characteristic of autism and can magnify sounds to an intolerable level, can lead to everyday classroom and playground noises such as shrieks and chatter being a source of anxiety and distraction. This impacts on a pupil’s ability to concentrate in the classroom and to socialise with others, further increasing isolation and a sense of being ‘different.’

    It was also found that pupils with autism who developed supportive friendships and felt accepted by classmates said this helped alleviate their social difficulties and made them feel good about themselves.

    These findings suggest it is crucial for schools to create a culture of acceptance for all pupils to ensure the long term wellbeing of pupils with autism in mainstream settings.

    Lead author of the paper Dr Emma Williams, from the University of Surrey, said: “Inclusive mainstream education settings may inadvertently accentuate the sense of being ‘different’ in a negative way to classmates.

    “We are not saying that mainstream schools are ‘bad’ for pupils with autism, as other evidence suggests they have a number of positive effects, including increasing academic performance and social skills.

    “Rather, we are suggesting that by cultivating a culture of acceptance of all and making small changes, such as creating non-distracting places to socialise, and listening to their pupils’ needs, schools can help these pupils think and feel more positively about themselves.

    “With over 100,000 children in the UK diagnosed with autism, it is important that we get this right to ensure that pupils with autism get the education they deserve and leave school feeling accepted, loved and valued, rather than with additional mental health issues.”


  7. Study suggests potential treatment for autism, intellectual disability

    November 26, 2017 by Ashley

    From the University of Nebraska Medical Center (UNMC) press release:

    A breakthrough in finding the mechanism and a possible therapeutic fix for autism and intellectual disability has been made by a University of Nebraska Medical Center researcher and his team at the Munroe-Meyer Institute (MMI).

    Woo-Yang Kim, Ph.D., associate professor, developmental neuroscience, led a team of researchers from UNMC and Creighton University into a deeper exploration of a genetic mutation that reduces the function of certain neurons in the brain.

    Dr. Kim’s findings were published in this week’s online issue of Nature Neuroscience.

    “This is an exciting development because we have identified the pathological mechanism for a certain type of autism and intellectual disability,” Dr. Kim said.

    Recent studies have shown that the disorder occurs when a first-time mutation causes only one copy of the human AT-rich interactive domain 1B (ARID1B) gene to remain functional, but it was unknown how it led to abnormal cognitive and social behaviors.

    Autism spectrum disorder (ASD) impairs the ability of individuals to communicate and interact with others. About 75 percent of individuals with ASD also have intellectual disability, which is characterized by significant limitations in cognitive functions and adaptive behaviors.

    There are no drugs or genetic treatments to prevent ASD or intellectual disability; the only treatment options focus on behavioral management and educational and physical therapies.

    The team created and analyzed a genetically modified mouse and found that a mutated Arid1b gene impairs GABA neurons, the ‘downer’ neurotransmitter, leading to an imbalance of communication in the brain.

    GABA blocks impulses between nerve cells in the brain. Low levels of GABA may be linked to anxiety or mood disorders, epilepsy and chronic pain. It counters glutamate (the upper neurotransmitter), as the two mediate brain activation in a Yin and Yang manner. People take GABA supplements for anxiety.

    “In normal behavior, the brain is balanced between excitation and inhibition,” Dr. Kim said. “But when the inhibition is decreased, the balance is broken and the brain becomes more excited causing abnormal behavior.

    “We showed that cognitive and social deficits induced by an Arid1bmutation in mice are reversed by pharmacological treatment with a GABA receptor modulating drug. And, now we have a designer mouse that can be used for future studies.”

    Next steps for Dr. Kim and his team are to even further refine the specific mechanism for autism and intellectual disability and to identify which of the many GABA neurons are specifically involved.


  8. Potential new autism drug shows promise in mice

    November 24, 2017 by Ashley

    From the Scripps Research Institute press release:

    Scientists have performed a successful test of a possible new drug in a mouse model of an autism disorder. The candidate drug, called NitroSynapsin, largely corrected electrical, behavioral and brain abnormalities in the mice.

    NitroSynapsin is intended to restore an electrical signaling imbalance in the brain found in virtually all forms of autism spectrum disorder (ASD).

    “This drug candidate is poised to go into clinical trials, and we think it might be effective against multiple forms of autism,” said senior investigator Stuart Lipton, M.D., Ph.D., Professor and Hannah and Eugene Step Chair at The Scripps Research Institute (TSRI), who is also a clinical neurologist caring for patients.

    The research, published on today in the journal Nature Communications, was a collaboration involving scientists at the Scintillon Institute; the University of California, San Diego School of Medicine; Sanford Burnham Prebys Medical Discovery Institute and other institutions. Lipton’s fellow senior investigators on the project were Drs. Nobuki Nakanishi and Shichun Tu of the Scintillon Institute in San Diego.

    ASD is brain development disorder that affects 1 in 68 children in the United States alone. Because ASD has been diagnosed more often in recent years, most Americans now living with autism diagnoses are children — roughly 2.4 percent of boys and 0.5 percent of girls.

    Genetic Analysis Leads to Potential Treatment

    The new study stemmed from a 1993 study in which Lipton and his laboratory, then at Harvard Medical School, identified a gene called MEF2C as a potentially important factor in brain development.

    This breakthrough led Lipton and colleagues to the discovery that disrupting the mouse version of MEF2C in the brain, early in fetal development, causes mice to be born with severe, autism-like abnormalities. Since that discovery in mice in 2008, other researchers have reported many cases of children who have a very similar disorder, resulting from a mutation to one copy of MEF2C (human DNA normally contains two copies of every gene, one copy inherited from the father and one from the mother). The condition is now called MEF2C Haploinsufficiency Syndrome (MHS).

    “This syndrome was discovered in people only because it was first discovered in mice — it’s a good example of why basic science is so important,” Lipton said.

    MEF2C encodes a protein that works as a transcription factor, like a switch that turns on the expression of many genes. Although MHS accounts for only a small proportion of autism disorder cases, large-scale genomic studies in recent years have found that mutations underlying various autism disorders frequently involve genes whose activity is switched on by MEF2C.

    “Because MEF2C is important in driving so many autism-linked genes, we’re hopeful that a treatment that works for this MEF2C-haploinsufficiency syndrome will also be effective against other forms of autism,” Lipton said, “and in fact we already have preliminary evidence for this.”

    For the study, the researchers created a laboratory model of MHS by engineering mice to have — like human children with MHS — just one functioning copy of the mouse version of MEF2C, rather than the usual two copies. The mice showed impairments in spatial memory, abnormal anxiety and abnormal repetitive movements, plus other signs consistent with human MHS. Analyses of mouse brains revealed a host of problems, including an excess in key brain regions of excitatory signaling (which causes neurons to fire) over inhibitory signaling (which suppresses neuronal activity).

    In short, these two important kinds of brain signals were out of balance. A similar excitatory/inhibitory (E/I) imbalance is seen in most forms of ASD and is thought to explain many of the core features of these disorders, including cognitive and behavioral problems and an increased chance of epileptic seizures.

    The researchers treated the MHS-mice for three months with NitroSynapsin, an aminoadamantane nitrate compound related to the Alzheimer’s FDA-approved drug memantine, which was previously developed by Lipton’s group. NitroSynapsin is known to help reduce excess excitatory signaling in the brain, and the team found that the compound did reduce the E/I imbalance and also reduced abnormal behaviors in the mice and boosted their performance on cognitive/behavioral tests — in some cases restoring performance essentially to normal.

    Lipton and colleagues are currently testing the drug in mouse models of other autism disorders, and they hope to move NitroSynapsin into clinical trials with a biotechnology partner.

    The work also has support from parents of children with MHS. “We are all hanging on to the hope that one day our children will be able to speak, to understand and to live more independent lives,” said Michelle Dunlavy, who has a son with MHS.

    In fact, Lipton’s group is also now using stem cell technology to create cell-based models of MHS with skin cells from children who have the syndrome — and NitroSynapsin appears to work in this ‘human context’ as well. Dunlavy and other parents of children with MHS recently organized an international, Facebook-based support group, which is coordinating to assist in Lipton’s research going forward.

    In an amazing twist, the scientific team also found in Alzheimer’s disease models that the new NitroSynapsin compound improves synapse function, the specialized areas for communication between nerve cells. Thus, the ability of the drug to improve ‘network’ communication in the brain may eventually lead to its use in several neurological diseases.


  9. Study uses stem cells to explore the causes of autism

    November 17, 2017 by Ashley

    From the Elsevier press release:

    Using human induced pluripotent stem cells (iPSCs) to model autism spectrum disorder (ASD), researchers at the University of São Paulo, Brazil and University of California, San Diego have revealed for the first time that abnormalities in the supporting cells of the brain, called astrocytes, may contribute to the cause of the disorder. The findings, published in Biological Psychiatry, help explain what happens at a biological level to produce ASD behavior, and may help researchers identify new treatments for patients with the disorder.

    Astrocytes play an important role in the development and function of the nervous system. But until now, iPSC models of autism have neglected their contribution. The new study, led by Dr. Patricia Beltrão-Braga and Dr. Alysson Muotri, used iPSCs to generate neurons and astrocytes to model the interaction between these brain cells and better understand how the brain forms in the disorder.

    “This new use of pluripotent stem cells suggests that neurobiological approaches to autism based solely on abnormal neuronal development may fail to account for complex interplay of neurons and astrocytes that may be an underappreciated component of the biology of this disorder,” said Dr. John Krystal, Editor of Biological Psychiatry.

    Induced pluripotent stem cell technology allows researchers to reprogram human cells into any cell in the body. In the study, first authors Dr. Fabiele Russo and Beatriz Freitas and colleagues used cells from three patients diagnosed with ASD and three healthy individuals to generate neurons and astrocytes. Neurons derived from ASD patients had less complex structure than healthy neurons, but adding healthy astrocytes to the ASD neurons improved their poorly developed structure. In reverse, pairing ASD astrocytes with healthy neurons interfered with their development, making them look more like the neurons from ASD patients.

    “The article highlights for the first time the influence of astrocytes in ASD, revealing that astrocytes play a fundamental role in neuronal structure and function,” said Beltrão-Braga.

    The researchers further investigated how the astrocytes exert their influence, and pegged a substance that astrocytes produce called IL-6, already suggested as a player in ASD, as the culprit for the defects. Astrocytes from the patients with ASD appeared to be producing too much of the substance, and the findings suggest that reducing IL-6 could be a beneficial treatment for neurons in ASD.

    Importantly, ASD has been a challenging disease to model using iPSCs because of its complexity. Several genes have been linked to ASD, but their contributions remain unknown, and genetic differences between patients have made it difficult to understand the cause and develop treatments for the disorder. But in this study, the ASD subjects were selected because they shared similar behaviors, rather than similar genes. According to Beltrão-Braga, this means the findings could provide a new alternative strategy for treating ASD symptoms, independent of the patient’s genotype.


  10. Study suggests brain activity is inherited, may inform treatment for ADHD, autism

    November 13, 2017 by Ashley

    From the Oregon Health & Science University press release:

    Every person has a distinct pattern of functional brain connectivity known as a connectotype, or brain fingerprint. A new study conducted at OHSU in Portland, Oregon, concludes that while individually unique, each connectotype demonstrates both familial and heritable relationships. The results published today in Network Neuroscience.

    “Similar to DNA, specific brain systems and connectivity patterns are passed down from adults to their children,” said the study’s principal investigator Damien Fair, Ph.D., P.A.-C., associate professor of behavioral neuroscience and psychiatry, OHSU School of Medicine. “This is significant because it may help us to better characterize aspects of altered brain activity, development or disease.”

    Using two data sets of functional MRI brain scans from more than 350 adult and child siblings during resting state, Fair and colleagues applied an innovative technique to characterize functional connectivity and machine learning to successfully identify siblings based on their connectotype.

    Through a similar process, the team also distinguished individual sibling and twin pairs from unrelated pairs in both children and adults.

    “This confirms that while unique to each individual, some aspects of the family connectome are inherited and maintained throughout development and may be useful as early biomarkers of mental or neurological conditions,” said lead author Oscar Miranda-Dominguez, Ph.D., research assistant professor of behavioral neuroscience, OHSU School of Medicine.

    Overall, the connectotype demonstrated heritability within five brain systems, the most prominent being the frontoparietal cortex, or the part of the brain that filters incoming information. The dorsal attention and default systems, important for attention or focus and internal mental thoughts or rumination, respectively, also showed significant occurrences.

    “These findings add to the way we think about normal and altered brain function,” said Fair. “Further, it creates more opportunity for personalized and targeted treatment approaches for conditions such as ADHD or autism.”