By Peter Mundy Since the modern era of research on autism began in the 1980s, questions about social cognition and social brain development have been of central interest to researchers. This year marks the 20th anniversary of the first annual meeting of the International Society for Autism Research (INSAR), and it is evident in this year’s meeting that the growth of social-cognitive neuroscience over the past two decades has significantly enriched autism science. For those unfamiliar with the term, social-cognitive neuroscience is the study of the brain systems that are involved in the causes and effects of social behaviors and social interaction. Some of these involve brain systems involved in thinking about other people’s thoughts or intentions, empathizing, social motivation and the impact of social attention on an individual’s thinking and emotions. At the same time, research with and for autistic people has also enriched social-cognitive neuroscience and the understanding of how our social minds develop. Autism spectrum disorder (ASD) is a complex and heterogeneous part of the human condition, or neurodiversity. It is associated with a wide range of life outcomes, from “disorder” or the profound challenges that encumber about 30 percent of affected individuals with minimal language and intellectual disability, to “differences” among people who have well-above-average abilities and accomplishments. Regardless of their outcomes, though, people on the autism spectrum travel a different path of social-cognitive neurodevelopment that appears to begin in infancy. For example, many experience some level of difficulty with social-cognitive mentalizing, also known as “theory of mind”—the mental representation of other people’s thoughts, perspectives, beliefs, intentions or emotions, which enables us to understand or predict their behaviors. © 2021 Scientific American

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 13: Memory and Learning
Link ID: 27824 - Posted: 05.19.2021

by Laura Dattaro Many genes linked to autism, schizophrenia and developmental delay share the same functions: They regulate the expression of other genes and support communication between neurons, according to an unpublished study. Researchers presented the findings virtually today at the 2021 International Society for Autism Research annual meeting. (Links to abstracts may work only for registered conference attendees.) Hundreds of genes with diverse functions are linked to autism, but how each contributes to the condition is unclear. In the new work, researchers analyzed the functions of 102 autism-linked genes that previous studies identified by comparing the genetic sequences of thousands of people with autism and those with other conditions, along with their family members and controls. “The genes identified give us an unprecedented opportunity to follow the biology, follow the genetics, to ask the question, where does this converge on function?” said lead investigator Stephan Sanders while presenting the work. Sanders is associate professor of psychiatry at the University of California, San Francisco. Other researchers are studying convergence in 3D brain models called organoids and looking for neuroanatomical similarities and differences across different animal models of autism, including mice and frogs. “Distinguishing causal functions from non-causal functions of these genes is a massive challenge,” Sanders says, and finding points of convergence could help. “The ultimate goal is to identify why disrupting these genes leads to autism.” © 2021 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 16: Psychopathology: Biological Basis of Behavior Disorders
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 12: Psychopathology: The Biology of Behavioral Disorders
Link ID: 27808 - Posted: 05.08.2021

by Peter Hess Deleting the autism-related gene CHD8 from the intestines induces significant gastrointestinal and behavioral changes in mice, according to a new unpublished study. The results suggest that changes to the gut are involved in some of the behavioral traits seen in people with CHD8 mutations, says lead researcher Evan Elliott, assistant professor of molecular and behavioral neuroscience at Bar-Ilan University in Ramat Gan, Israel. Elliott’s team presented the findings virtually this week at the 2021 International Society for Autism Research annual meeting. (Links to abstracts may work only for registered conference attendees.) Up to 90 percent of people with CHD8 mutations report gastrointestinal issues such as constipation, Elliott says. Most also have autism. Mice missing one copy of CHD8 have unusually thin and permeable small intestines, Elliott and his colleagues found. The reason seems to be that these mice have fewer mucus-producing goblet cells than controls, resulting in thinner organ walls and less mucus lining the digestive tract. CHD8 regulates the expression of other genes, so Elliott’s team looked at gene expression levels in the CHD8 mice’s intestinal epithelial cells via RNA sequencing. The mice expressed 920 genes differently than control mice did. These include an increase in the expression of genes involved in inflammatory responses and in antimicrobial activity. The latter set may be the body’s way of compensating for increased microbial populations, Elliott says. © 2021 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 13: Homeostasis: Active Regulation of the Internal Environment
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 9: Homeostasis: Active Regulation of the Internal Environment
Link ID: 27801 - Posted: 05.05.2021

by Angie Voyles Askham A brain circuit that connects the amygdala to the hypothalamus is essential for deriving pleasure from social interactions, according to a new study in mice. Alterations in this circuit may help explain why autistic people tend to have less social motivation than their non-autistic peers. The release of the neurotransmitter dopamine into the striatum prompts the rewarding feelings that come from stimuli such as food or sex, previous research shows. But it was unclear whether all social reward is processed in that same circuit, or if it occurs in a separate brain area that later links up with the striatum, the brain’s reward center, says lead researcher Weizhe Hong, associate professor of neurobiology and biological chemistry at the University of California, Los Angeles. Hong and his colleagues trained mice on a social test and then altered activity in the animals’ medial amygdala, which has been linked to the regulation of social behaviors. Cells in the area carry information about social reward to the medial preoptic area of the hypothalamus, the team found. And activation of this circuit prompts the release of dopamine in the striatum. “It’s filling a gap that existed” in the field, says Jessica Walsh, assistant professor of pharmacology at the University of North Carolina at Chapel Hill, who was not involved in the study. © 2021 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 4: Development of the Brain
Link ID: 27793 - Posted: 05.01.2021

by Angie Voyles Askham A dearth of insulation around neuronal projections may explain why some parts of the cerebral cortex can appear thicker in brain scans of autistic people than in those of non-autistic people, according to a new study. Magnetic resonance imaging (MRI) studies show that some autistic children have bigger brains than their non-autistic peers, with much of the overgrowth occurring in the cerebral cortex. The reason for this difference remains unclear, but it seems to reflect an apparent excess of gray matter, which consists of neuronal cell bodies, relative to white matter, composed of neuronal projections. Newly developed neurons in the brains of autistic people may have trouble migrating to the proper place, some researchers have suggested, which could blur the boundary between gray and white matter in some regions and cause the gray matter to look thicker on an MRI scan. But higher levels of myelin, the insulation that surrounds neuronal projections, in non-autistic people could also skew these measures, says lead researcher of the new work, Mallar Chakravarty, associate professor of psychiatry at McGill University in Montreal. Myelin appears brighter on an MRI scan than other tissue, so an abundance of it near the boundary between gray and white matter could make the gray matter appear thinner, he says. © 2021 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 2: Functional Neuroanatomy: The Cells and Structure of the Nervous System
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 2: Neurophysiology: The Generation, Transmission, and Integration of Neural Signals
Link ID: 27783 - Posted: 04.24.2021

by Peter Hess Dysfunction in a brain circuit that regulates movement may contribute to some of the motor learning difficulties associated with autism, according to a new mouse study. The mice lack one copy of a chromosomal region called 16p11.2. Up to about one-third of people with this deletion have autism, and some have speech and motor problems. Most autistic people have motor difficulties and show delays in developmental milestones such as standing and walking. The 16p mice, too, are slow to learn new motor tasks, such as balancing on a spinning rod. The explanation seems to be a shortage of the neurotransmitter noradrenaline in the motor cortex, which helps coordinate and execute movements. The dearth originates in the locus coeruleus, a part of the brainstem that serves as the brain’s main source of the chemical. “Noradrenaline is known to be involved in modulating the excitability of neurons,” says lead researcher Simon Chen, assistant professor of cellular and molecular medicine at the University of Ottawa in Ontario, Canada. “When there’s low noradrenaline in the motor cortex and the mouse is learning a movement, it takes them longer for the neural circuits to consolidate neurons that are important to control movement.” The learning process is similar for people, Chen says. When learning how to walk, for instance, a child loses her footing and falls many times. But once in a while, she will take a few more steps than she did in the previous attempt, and the brain remembers the movement that made that possible. © 2021 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 5: The Sensorimotor System
Link ID: 27769 - Posted: 04.14.2021

by Angie Voyles Askham Mice that lack CNTNAP2, a gene linked to autism, have an atypical collection of microbes in their intestines, according to a new study. Treating the mice with a strain of gut bacteria commonly found in wildtype mice, people and other mammals improves their social behavior. The CNTNAP2 mice are hyperactive, and those raised in isolation prefer to spend time alone or with a familiar cagemate rather than with a stranger mouse. But when they grow up alongside wildtype littermates, their social deficits — but not their hyperactivity — disappear, the study shows. Because mice that live together eat one another’s feces, which can alter the microbial content of their guts, the researchers wondered if a change in the microbiome might be driving the change in the isolated animals’ social behaviors. “It was sort of a serendipitous discovery,” says lead investigator Mauro Costa-Mattioli, professor of neuroscience at Baylor College of Medicine in Houston, Texas. The findings highlight how some autism traits associated with genetic mutations may be shaped, and potentially eased, via changes to the gut microbiome. Figuring out which behaviors can be attributed to the environment is particularly helpful for thinking about treatments because the environment can be changed, whereas “genetics is still hard to correct,” says Sarkis Mazmanian, professor of microbiology at the California Institute of Technology in Pasadena, who was not involved in the work. © 2021 Simons Foundation

Related chapters from BN: Chapter 13: Homeostasis: Active Regulation of the Internal Environment; Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 9: Homeostasis: Active Regulation of the Internal Environment; Chapter 13: Memory and Learning
Link ID: 27746 - Posted: 03.27.2021

by Charles Q. Choi Blood levels of proteins associated with the autism-linked gene PTEN could influence the course of the condition, according to a new study. Tests measuring these molecules could also help clinicians diagnose autism and other neurological conditions, and chart their trajectories, the researchers say. “We might be able to make useful clinical predictions about outcomes that can help to tailor interventions earlier and to help patients and families plan for what is needed,” says lead investigator Thomas Frazier, professor of psychology at John Carroll University in University Heights, Ohio. The PTEN gene encodes a protein that suppresses tumors and also influences the connections between neurons. Mutations in PTEN are linked not only to benign tumors and several types of cancer, but also to autism and macrocephaly, or an unusually large head. Much remains unknown, however, about why PTEN mutations can affect people with and without autism differently. For example, PTEN mutations are often associated with impaired mental function in autistic people but not as often in non-autistic people, whose traits can vary widely. In the new study, Frazier and his colleagues examined how the mutations affect blood levels of not just PTEN protein, but also the proteins it interacts with. Molecular links: The team assessed the blood levels of various proteins — as well as intelligence quotient (IQ) and other factors related to mental function — in 25 autistic and 16 non-autistic participants with PTEN mutations and macrocephaly, all about 9 years old on average. The researchers also examined 20 participants, about 14 years old on average, with autism, macrocephaly and no PTEN mutations. © 2021 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 13: Memory and Learning
Link ID: 27711 - Posted: 02.28.2021

by Laura Dattaro Genetic variants that contribute to autism may also be involved in attention deficit hyperactivity disorder (ADHD) and Tourette syndrome, according to a new study. In 2019, researchers from the Psychiatric Genomics Consortium linked variants associated with autism to seven neuropsychiatric conditions, including anorexia, bipolar disorder and schizophrenia. Despite the genetic overlap, though, some of those conditions, such as anorexia and Tourette syndrome, don’t tend to co-occur. The new work homes in on Tourette syndrome — a motor and tic condition — and three diagnoses that often present with it: More than half of people with Tourette also have obsessive-compulsive disorder (OCD) or ADHD, and up to 20 percent have autism. Because all four conditions can involve impulsive and compulsive behaviors, some scientists have proposed that they exist along a spectrum, with ADHD on one end, OCD on the other, and autism and Tourette in the middle. The goal of looking at all the conditions on this spectrum together is to elucidate the genetics underlying their traits, says lead investigator Peristera Paschou, associate professor of biological sciences at Purdue University in West Lafayette, Indiana. “There is a lot of value in zooming out and trying to think across what would be strict diagnostic categories,” Paschou says. Gene associations: The researchers analyzed data from previous studies that involved a total of 93,294 people with at least one of the four conditions, along with 51,311 controls. They looked at common variants — single-letter changes to DNA that appear in more than 1 percent of the population — shared by any two of the four conditions. © 2021 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 16: Psychopathology: Biological Basis of Behavior Disorders
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 12: Psychopathology: The Biology of Behavioral Disorders
Link ID: 27676 - Posted: 02.03.2021

by Peter Hess Mice missing a copy of the autism-linked gene MAGEL2 have trouble discerning between a familiar mouse and an unfamiliar one, but treating them with the social hormone vasopressin reverses this deficit, according to a new study. Mutations in or deletions of MAGEL2 are linked to autism and several related conditions, including Prader-Willi syndrome, which is characterized by intellectual disability, poor muscle tone, difficulty feeding and problems with social interactions. The new findings suggest that these social issues in people stem from impairments in vasopressin’s function in a brain region called the lateral septum, which relays signals between the hippocampus and the ventral tegmental area. They also hint that vasopressin treatment could remedy those issues, says Elizabeth Hammock, assistant professor of psychology and neuroscience at Florida State University in Tallahassee, who was not involved with the study. A 2020 study showed that low levels of vasopressin in cerebrospinal fluid can flag many infants who are later diagnosed with autism. But clinical trials have shown that either providing vasopressin or blocking its effects can improve social communication in autistic children. Because of these seemingly contradictory results, “a better understanding of how alterations in the vasopressinergic system leads to social deficits and how vasopressin administration could resolve some of these problems was needed,” says co-lead researcher Freddy Jeanneteau, professor of neuroscience at Montpellier University in Montpellier, France. © 2021 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 5: Hormones and the Brain
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 8: Hormones and Sex
Link ID: 27665 - Posted: 01.27.2021

by Angie Voyles Askham Mutations that affect a histone called H3.3 can lead to a neurodegenerative condition marked by developmental delay and congenital anomalies, according to a new study. Histones act as spools for DNA, making it possible to pack the strands of genetic material tightly within the nucleus. They also serve as gatekeepers for protein production, physically blocking proteins from interacting with genes, or allowing them access to turn genes on and off. Autism has been tied to mutations in proteins that modify histones and disrupt this gatekeeping process. The new work is among the first to link atypical neurodevelopment and degeneration to mutations that affect a histone itself. It focuses on 46 people with a mutation in either of two genes that code for H3.3. All have a diagnosis of developmental delay. Many also have other medical conditions, such as seizures, heart defects and atypical development of the head and face. “We see this [result] as a Rosetta Stone,” says lead researcher Elizabeth Bhoj, assistant professor of pediatrics and human genetics at the University of Pennsylvania. In addition to providing information about this particular cohort, the findings could help explain the role that histones play in neurodevelopmental conditions in general, she says. Earlier studies have associated H3.3 with cancer, but none of the participants in the new study have tumors. About 21 percent, however, show signs of neurodegeneration, and 26 percent have shrinkage in the cerebral cortex, the brain’s outer layer, suggesting the condition may be progressive. “It’s an impressive collection of novel mutations that seem to be converging on a set of clinical features,” says James Noonan, associate professor of genetics and neuroscience at Yale School of Medicine, who was not involved in the study. © 2021 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 13: Memory and Learning
Link ID: 27660 - Posted: 01.23.2021

by Sarah DeWeerdt Children with autism may have a subtly different set of bacteria in their gut than their non-autistic siblings, according to unpublished data presented virtually on Tuesday at the 2021 Society for Neuroscience Global Connectome. The prospect that manipulating the microbiome could ease gastrointestinal problems and other autism traits has tantalized many families of autistic children. But studies of the gut microbiome in people with autism are scarce and have shown conflicting results, and mouse studies can be difficult to interpret. For the new work, researchers recruited 111 families that each have two children — one with autism and one without — born within two years of each other and aged 2 to 7 years old. “We tried to be as careful as possible by using a control cohort that were siblings,” says study leader Maude David, assistant professor of microbiology at Oregon State University in Corvallis. This study design helped control for variables such as household environment, pets and other factors that can shape the microbiome, she says. The researchers collected stool samples from the children at three time points, two weeks apart. The repeated sampling reduced the likelihood that short-term shifts in the children’s gut microbiome — due to transient environmental influences, such as day-to-day dietary changes — would skew the results. © 2021 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 13: Homeostasis: Active Regulation of the Internal Environment
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 9: Homeostasis: Active Regulation of the Internal Environment
Link ID: 27644 - Posted: 01.15.2021

Our staff took a look back at the papers we wrote about in 2020 that most shaped our understanding of autism and how to diagnose or treat it. Despite the chaos of this year, there were many to consider. But we reviewed them all, asked some researchers for input and winnowed the list down to 10. Some of our selections highlight new insights into factors that influence autism traits, including fever, mitochondria and exons — the protein-coding parts of genes. Others expand our understanding of the genes and genetic regions linked to autism, as well as their roles in related conditions. Two new gene therapies for autism-related syndromes also caught our eye. And we single out a study of the sperm from men who have children on the spectrum, and a look at what happens to the toddlers who screen positive for autism. Here are our picks for the past year’s most notable papers, in reverse chronological order. DNA helix1. Mutations in the same exon linked to similar autism traits People with autism who carry DNA variants in the same exon, or protein-coding region of a gene, have more similar cognitive abilities and behaviors than those who carry mutations in different regions of the same gene, this study found. A separate study detailed how one particular exon contributes to social behavior and cognitive abilities in mice; a third paper described a new tool that helps researchers determine how mutations in an exon affect the number of protein isoforms a gene can express. © 2021 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 13: Memory and Learning
Link ID: 27641 - Posted: 01.09.2021

by Sarah DeWeerdt A drug that has been tested in clinical trials as a treatment for depression restores social memory in a mouse model of 22q11.2 deletion syndrome, according to a new study. The findings hint that the drug might also be useful to treat social cognitive difficulties in people with conditions such as autism, experts say. People who are missing one copy of a chromosomal region known as 22q11.2 have heart abnormalities, distinctive facial features and an increased risk of schizophrenia and other psychiatric conditions. About 16 percent have autism. People with the syndrome also have a smaller-than-average hippocampus, a structure that functions as the brain’s memory hub. The findings extend what researchers know about the role of the hippocampus in social behavior by suggesting that a small region of the hippocampus known as CA2 springs to life when an animal encounters an individual it hasn’t met before. A strength of the study is that it describes the basic biology of a brain circuit, shows how that circuit is disrupted in a mouse model and identifies a therapeutic target to reverse those disruptions, says Anthony LaMantia, professor of developmental disorders and genetics at Virginia Polytechnic Institute and State University in Blacksburg, who was not involved in the work. “This is one of the best papers sort of going from soup to nuts that has come out.” Previous studies showed that CA2 is crucial for social memory, the ability to recognize and remember others. “But we really didn’t have a good handle on what type of information CA2 was providing to the rest of the brain,” says study leader Steven Siegelbaum, professor of neuroscience and pharmacology at Columbia University. © 2020 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 17: Learning and Memory
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 13: Memory and Learning
Link ID: 27635 - Posted: 12.22.2020

by Peter Hess Two types of neurons process social information, a new mouse study suggests, but only one is disrupted in mice missing the autism-linked gene FMR1. The neurons reside in a brain region called the hypothalamus, and both send signals via the hormone oxytocin. The deletion of FMR1, however, affects these cells differently: The loss of FMR1 in the smaller, ‘parvocellular’ neurons diminishes the mice’s interest in social interactions — but only those involving peers, the new work shows. The gene’s loss from the larger, ‘magnocellular’ neurons, by contrast, does not disrupt the animals’ interactions with either peers or parents. “There are a lot of different types of social behaviors, and not all of them are impaired in autism,” says lead investigator Gül Dölen, assistant professor of neuroscience at Johns Hopkins University in Baltimore, Maryland. Whereas peer-to-peer social interactions are troublesome for many autistic people, other social interactions — such as parental connections — are on par with those seen in non-autistic people, she says. This new understanding of the different neurons’ functions could help explain why clinical trials of oxytocin for treating autism traits have shown mixed results. It could also help scientists develop more effective treatments, experts say. “There are these two different kinds of neurons that we’ve known about for a really long time, and each of their contributions to social behavior has never really been dissected out,” says Larry Young, chief of behavioral neuroscience and psychiatric disorders at Emory University in Atlanta, Georgia, who was not involved with the study. “It’s really important for the future of drug development.” © 2020 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 5: Hormones and the Brain
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 8: Hormones and Sex
Link ID: 27632 - Posted: 12.19.2020

by Laura Dattaro In 1983, psychologist Christopher Gillberg posed a provocative question to the readers of the British Journal of Psychiatry: Could autism and anorexia nervosa share underlying causes? Gillberg’s curiosity came in part from his observations of three autistic boys whose female cousins all had the eating disorder, which is characterized by food restrictions, low body weight, an intense fear of gaining weight and a distorted body image. Gillberg, professor of child and adolescent psychiatry at the University of Gothenburg in Sweden, initially suggested that anorexia is the ‘female form of autism.’ Although that idea wasn’t entirely accurate, his suspicions that eating disorders and autism are linked have borne out: People with anorexia are more likely to be autistic than those without it, studies show. There are fewer data demonstrating that autistic people are at particularly high risk for eating disorders, but experts say it’s likely. How often do anorexia and autism overlap? Estimates vary, though most researchers agree that roughly 20 percent of people with anorexia are autistic. Both conditions are rare — about 1 percent of people are autistic and 0.3 percent have anorexia — and most research so far has examined the prevalence of autism in people with anorexia, not the reverse. Among 60 women receiving treatment for an eating disorder at a clinic in the United Kingdom, for example, 14 of them, or 23 percent, scored above the diagnostic cutoff on a test called the Autism Diagnostic Observation Schedule (ADOS). Similarly, about one-third of people with anorexia have been diagnosed with autism, according to a long-running study that has followed 51 people with anorexia and 51 controls in Sweden since the 1980s. © 2020 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 13: Homeostasis: Active Regulation of the Internal Environment
Related chapters from MM:Chapter 4: Development of the Brain; Chapter 9: Homeostasis: Active Regulation of the Internal Environment
Link ID: 27616 - Posted: 12.09.2020

by Angie Voyles Askham Many people with mutations that disrupt a gene called NCKAP1 have autism or autism traits — along with speech and language problems, motor delays and learning difficulties — according to a new study. The results, from a large international team of researchers and clinicians, clarify how mutations in NCKAP1 affect people and solidify its position as a top autism gene. Sequencing studies over the past decade have turned up three autistic people with de novo, or non-inherited, variants that likely disrupt NCKAP1, putting it on a list of genes strongly tied to autism. Other work has shown that mice that do not express the gene have atypical brain development. But those reports contain little information about the outward characteristics of people with NCKAP1 mutations — which are challenging to study because variants in the gene are rare, says Hui Guo, associate professor of life sciences at Central South University in Changsha, China. In the new work, Guo teamed up with scientists and clinicians across the globe to identify and characterize 18 additional people with NCKAP1 mutations. “This study demonstrates that international cooperation among many institutions is becoming fundamental to advancing our understanding of rare variants,” says Abha Gupta, assistant professor of pediatrics at Yale University, who was not involved in the study. Painting a detailed picture of traits associated with NCKAP1 mutations can also improve a person’s chance of being diagnosed and provide guidance about expected outcomes, she says. Guo asked colleagues who collect genetic data for other research to sift through their records for people with NCKAP1 variants. He also used GeneMatcher, a site that connects researchers to clinicians interested in the same genetic variants. © 2020 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 4: Development of the Brain
Link ID: 27611 - Posted: 12.07.2020

by Laura Dattaro Autistic boys with large brains in early childhood still have large brains in adolescence, according to a new study. Autistic girls, too, have brains that grow differently from those of their non-autistic peers. The findings challenge the long-standing idea that brain enlargement in autism is temporary. Previous studies indicated that young children on the spectrum have larger brains than their non-autistic peers but older people with autism do not. To explain the difference, researchers speculated that a pruning process follows early brain overgrowth. But the changes are a mirage, the researchers behind the new study say: Because having a large brain is associated with a low intelligence quotient (IQ) and severe autism traits, and because older children with such characteristics are often excluded from imaging studies, the prior results reflect only a lack of older participants with large brains. “This whole idea of this early overgrowth followed by normalization is just an artifact of sampling bias,” says lead investigator Christine Wu Nordahl, associate professor of psychiatry and behavioral sciences at the University of California, Davis MIND Institute. “It was sort of like, ‘Wow, why didn’t we ever think about this before?’ But it’s pretty clear that that’s what’s happening.” Autistic and non-autistic children also show different development patterns in their white matter — fibers that connect regions of the brain — in early childhood, a second study from Nordahl’s group shows. Some of the differences correlate with changes in the children’s autism traits over time. © 2020 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 2: Functional Neuroanatomy: The Cells and Structure of the Nervous System
Related chapters from MM:Chapter 4: Development of the Brain; Chapter 2: Neurophysiology: The Generation, Transmission, and Integration of Neural Signals
Link ID: 27598 - Posted: 11.30.2020

by Peter Hess / Mutations in a top autism gene called SYNGAP1 slow the rate at which zebrafish digest food and pass waste. The findings may explain why some people with SYNGAP1 mutations have gastrointestinal (GI) problems. Researchers presented the unpublished work on Tuesday and Wednesday at the 2020 International SYNGAP1 Scientific Conference, which took place virtually because of the coronavirus pandemic. They also began recruiting people with SYNGAP1 mutations at the meeting for an ongoing study of gut function. “It’s been in the literature, this link between GI symptoms and [autism], for a long time, with not a lot of progress on the mechanisms,” says lead researcher Julia Dallman, associate professor of biology at the University of Miami in Florida, who presented the findings on Wednesday. In the brain, SYNGAP1 functions mainly at synapses, or the junctions between neurons, and helps the cells exchange chemical messages. Mutations in the gene are strongly linked to autism, seizures, intellectual disability and sleep problems. Prompted by families’ anecdotal reports of constipation, reflux and overeating in people with SYNGAP1 mutations, Dallman and her colleagues decided to explore the gene’s role in the gut. The young zebrafish’s transparent skin allowed the researchers to trace the movement of microscopic fluorescent beads — mixed into the fish’s food — through the gut. In this way, they measured how quickly and how strongly the digestive tract moves food and waste. © 2020 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 13: Homeostasis: Active Regulation of the Internal Environment
Related chapters from MM:Chapter 4: Development of the Brain; Chapter 9: Homeostasis: Active Regulation of the Internal Environment
Link ID: 27590 - Posted: 11.21.2020

by Angie Voyles Askham Editing DNA in embryonic and newborn mice by using CRISPR technology can override mutations underlying Angelman syndrome and prevent many of the condition’s traits, according to a new study1. The effects last for at least 17 months and may be permanent, the researchers say. “It’s very exciting,” says Steven Kushner, professor of psychiatry at Columbia University, who was not involved in the study. Angelman syndrome usually stems from a mutation in or deletion of the UBE3A gene. People have two copies of the gene — one from each parent — but typically only the one passed down from the mother is active in neurons. Mutations that stymie that copy can lead to a lack of UBE3A protein in the brain, causing the syndrome’s core traits: developmental delays, motor dysfunction, speech impairments, seizures and, often, autism. These traits improve in response to treatments that activate the silent yet intact paternal copy of UBE3A and boost production of the protein in Angelman syndrome model mice2,3. But these treatments wear off over time, requiring repeated injections into the spinal fluid or brain. The new therapy is effective after only two doses, says lead researcher Mark Zylka, professor of cell biology and physiology at the University of North Carolina at Chapel Hill. The strategy uses the enzyme CRISPR-Cas9 to cut and edit DNA encoding an ‘antisense RNA’ molecule that ordinarily serves to block production of UBE3A protein from the paternal copy of the gene. The technique also rouses the silent paternal copy of the gene in cultured human neurons, suggesting that it might work in people. © 2020 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 4: Development of the Brain
Link ID: 27575 - Posted: 11.10.2020