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

By Giorgia Guglielmi, Spectrum A small clinical trial of a gene therapy for Angelman syndrome—a rare genetic condition related to autism—is on hold after two participants temporarily lost the ability to walk. The safety issue is important to resolve, experts say, given that the therapy otherwise appears to be effective, and the trial could guide treatment strategies for similar brain conditions. Biopharmaceutical company Ultragenyx in Novato, California, in collaboration with Florida-based biotech startup GeneTx, launched the trial in February to assess the safety of a therapy for Angelman syndrome, a neurodevelopmental condition characterized by intellectual disability, balance and motor problems, seizures, sleep problems and, in some cases, autism. Angelman syndrome results from the mutation or absence of a gene called UBE3A. People inherit two copies of UBE3A. Typically, only the maternal copy is active in neurons and the paternal copy is silent. But in people with Angelman syndrome, the maternal copy is mutated or missing, so their brain cells express no active UBE3A protein. The drug developed by Ultragenyx and GeneTx, called GTX-102, is a short snippet of RNA called an antisense oligonucleotide that activates the paternal copy of UBE3A and aims to restore the protein to typical levels. Three other companies—Roche, Biogen, and Ionis—are pursuing similar therapies for the syndrome. On 26 October, Ultragenyx and GeneTx reported that the clinical trial had enrolled five individuals with Angelman syndrome, aged 5 to 15. The plan had been to administer to each participant a dose of GTX-102 once a month over four months. Researchers injected the drug directly into the nutrient-rich solution that envelops the brain and spinal cord through a site in the lower back. © 2020 American Association for the Advancement of Science

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 4: Development of the Brain; Chapter 5: The Sensorimotor System
Link ID: 27572 - Posted: 11.07.2020

By Lydia Denworth, Spectrum, Brendan Borrell, Allyson Berent is a specialty veterinarian in New York City. She treats animals that other doctors cannot help. When no good therapies are available, she invents one. Cats and dogs consumed almost all of her time—until 6 years ago, when her second daughter was born. As a baby, Quincy appeared healthy and happy, smiling at an early age and giggling frequently. But during her first few months of life, she missed many developmental milestones: At 10 weeks, she was not making eye contact. When her parents waved toys in front of her, she stared blankly. She had trouble feeding. And when she was lying on her stomach, she could not lift her head. Doctors kept telling Berent and her husband to give it time, but the couple insisted on genetic testing: At 7 months old, their daughter was diagnosed with Angelman syndrome, a neurodevelopmental condition that affects as many as one in 12,000 people. Most people with Angelman syndrome have severe intellectual disability. They never talk or live an independent life. They experience seizures, gut issues, and sleeping and feeding difficulties. Due to balance and motor problems, they are usually unable or barely able to walk. Many also meet the diagnostic criteria for autism. Within days of learning her daughter’s diagnosis, Berent set herself a new goal: curing Quincy. With her medical background, she had no trouble parsing the scientific research on Angelman syndrome. She learned that it stems from a missing or mutated copy of a gene called UBE3A, which generates a protein essential for healthy brain activity. People inherit two copies of UBE3A, one from each parent, but the paternal copy is typically silent. In about 70% of people with Angelman, the maternal copy is absent, and they produce none of the protein. Many others with the syndrome have a small mutation in the mother’s copy, rendering it ineffective. © 2020 American Association for the Advancement of Science.

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: 27528 - Posted: 10.16.2020

by Angie Voyles Askham Autism is a neurodevelopmental condition. Although it is diagnosed based on the presence of two core behaviors — restricted interests and repetitive behaviors, as well as difficulties with social interactions and communication — those traits are thought to arise because of alterations in how different parts of the brain form and connect to one another. No research has uncovered a ‘characteristic’ brain structure for autism, meaning that no single pattern of changes appears in every autistic person. Studies of brain structure often turn up dissimilar results — there is great variety across individuals in general. But some trends have begun to emerge for subsets of autistic people. These differences might one day provide some insight into how some autistic people’s brains function. They may also point to bespoke treatments for particular subtypes of autism. Here is what we know about how brain structure differs between people with and without autism. Which brain regions are known to be structurally different between autistic and non-autistic people? Children and adolescents with autism often have an enlarged hippocampus, the area of the brain responsible for forming and storing memories, several studies suggest, but it is unclear if that difference persists into adolescence and adulthood1,2. © 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: 27526 - Posted: 10.16.2020

by Angie Voyles Askham Autistic people share some brain structure differences with people who have other neuropsychiatric conditions, including schizophrenia and attention deficit hyperactivity disorder (ADHD), according to a massive new brain-imaging study1. These shared differences stem from the atypical development of one particular type of neuron, the findings suggest. The results provide “further evidence that our understanding of autism can really be advanced by explicitly studying autism in the context of other disorders,” says Armin Raznahan, chief of the Section on Developmental Neurogenomics at the U.S. National Institute of Mental Health in Bethesda, Maryland, who was not involved in the study. The researchers looked at brain scans from 28,321 people to identify structural changes associated with any of six conditions: autism, ADHD, bipolar disorder, major depressive disorder, obsessive-compulsive disorder and schizophrenia. The team found that the brains of people with these conditions differ from controls in a specific way: They have similar patterns of thickness across the cortex, the brain’s outer layer. The cortical regions with the biggest differences in thickness are typically rich in a particular type of excitatory neuron. “We were able to put our fingers on what might be behind that commonality,” says lead researcher Tomas Paus, professor of psychology and psychiatry at the University of Toronto in Canada. “That was very exciting.” The work combined data from 145 cohorts within the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium, an international group of researchers who collect and analyze brain-scan data in a standardized way so that they can pool their results. © 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: 27503 - Posted: 10.03.2020

by Peter Hess / Some preterm babies who are later diagnosed with autism show increasing developmental delays during infancy, according to a new study1. This distinct pattern could help doctors identify autism in preterm babies and start them on therapies in infancy, says Li-Wen Chen, pediatric neurologist at National Cheng Kung University College of Medicine in Taiwan, who designed and conducted the study. About 7 percent of children born preterm are autistic, compared with 1 to 2 percent of children in the general population. Researchers cannot accurately predict which preterm babies are most likely to be later diagnosed with the condition, however. The new study tracked ‘very preterm’ babies — meaning those born more than 8 weeks prematurely and weighing 3.3 pounds or less — from birth to 5 years old. It shows that preterm autistic babies’ development deviates significantly from that of their non-autistic peers starting at 6 months of age. This split could flag preterm babies in need of behavioral interventions well before the typical age of an autism diagnosis, which is about 4 years in the United States. “This early trajectory work is really very valuable, because it means you shouldn’t be making predictions based on single observations,” says Neil Marlow, professor of neonatal medicine at University College London in the United Kingdom, who was not involved in the work. Autistic children who are born preterm score lower on measures of nonverbal behaviors important for social interactions than do autistic children who are born full-term, according to previous work by Chen’s team2. Those results also showed that autism traits are more similar among preterm children than among full-term children. © 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: 27493 - Posted: 09.28.2020

by Terje Falck-Ytter, Sofia Loden Historians and authors have given many famous figures an armchair diagnosis of autism over the years: Albert Einstein, Michelangelo and Thomas Jefferson, to name just a few. Looking for signs of autism in historical figures and fictional characters can give us important insight into society’s changing perceptions of the condition through time. But however intellectually interesting, we urge caution before labelling such figures actually autistic. Consider the idea that Perceval, one of the Knights of the Round Table in the King Arthur legend, was autistic — a claim levied by the literary scholar Paula Leverage1. If correct, it suggests that today’s fascination with portraying autism traits in popular culture — for example, in television shows such as “The Big Bang Theory” and novels such as “The Curious Incident of the Dog in the Night-Time” — has a near thousand-year-long history2. But given Perceval’s anti-heroism, comical and sometimes immoral behavior, describing him as autistic could also increase the risk for misconceptions and stigmatization of actual people with the condition. Adventure time: Perceval made his debut in “Le Conte du Graal” (The Story of the Grail), a rhymed verse romance written by the Old French poet Chrétien de Troyes in the late 12th century3. The tale describes Perceval’s many adventures, including his discovery of the famous grail — an ornate gold dish purported to have unusual powers and the object of fascination for numerous writers ever since the Middle Ages. © 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: 27486 - Posted: 09.25.2020

by Jonathan Moens Conversations between an autistic and a typical person involve less smiling and more mismatched facial expressions than do interactions between two typical people, a new study suggests1. People engaged in conversation tend to unconsciously mimic each other’s behavior, which may help create and reinforce social bonds. But this synchrony can break down between autistic people and their neurotypical peers, research shows. And throughout an autistic person’s life, these disconnects can lead to fewer opportunities to meet people and maintain relationships. Previous studies have looked at autistic people’s facial expressions as they react to images of social scenes on a computer screen2. The new work, by contrast, is one of a growing number of experiments to capture how facial expressions unfold during ordinary conversation. Changes in facial expressions are easy to observe but notoriously hard to measure, says lead investigator John Herrington, assistant professor of psychiatry at the Children’s Hospital of Philadelphia in Pennsylvania. He and his colleagues devised a new method to quantify these changes over time in an automated and granular way using machine-learning techniques. Atypical facial expressions are in part a manifestation of difficulties with social coordination, Herrington says. So tracking alterations in facial expression may be a useful way to monitor whether interventions targeting these traits are effective. The new study included 20 autistic people and 16 typical controls, aged 9 to 16 years and matched for their scores on intelligence and verbal fluency. Each participant engaged in two 10-minute conversations — first with their mother and then with a research assistant — to plan a hypothetical two-week trip. © 2020 Simons Foundation

Related chapters from BN: Chapter 15: Emotions, Aggression, and Stress; Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 11: Emotions, Aggression, and Stress; Chapter 4: Development of the Brain
Link ID: 27440 - Posted: 08.29.2020

by Angie Voyles Askham A new study pinpoints genes and cell types that may account for the atypical brain structure in people with genetic conditions related to autism1. The work offers insight into how the brain develops differently in people with these conditions and identifies new potential therapeutic targets, says Mallar Chakravarty, associate professor of psychiatry at McGill University in Montreal. Chakravarty has collaborated with the researchers previously but was not involved in the new work. The analysis considered people with six genetic conditions associated with atypical brain development, including syndromes associated with deletions in the chromosomal regions 11p13 and 22q11.2, both of which increase the likelihood of autism2. “We used known genetic conditions as a kind of foothold into the complex biology of neurodevelopmental disorders,” says lead researcher Armin Raznahan, chief of the Developmental Neurogenomics section at the U.S. National Institute of Mental Health intramural research program. Previous studies of mice with autism-linked genetic conditions have shown that brain structure changes tend to crop up in regions where the relevant genes are ordinarily expressed3. The same holds true for people, Raznahan and his colleagues found after comparing measurements from brain scans with existing data from postmortem brains. “It’s wildly creative,” Chakravarty says of the method. Raznahan and his colleagues used magnetic resonance imaging to scan the brains of 231 adolescents and adults with one of the six genetic conditions and 287 controls. Each of the six conditions results from a deletion or duplication of a chromosome or set of genes within a chromosome. © 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: 27430 - Posted: 08.22.2020

by Laura Dattaro Extra repeating bits of DNA may account for nearly 3 percent of the genetic architecture of autism, according to a new study1. The work is the first to examine such genetic variants in autism on a large scale. About half of the identified repeating sections occur in genes that have not been previously linked to autism, suggesting new lines of inquiry for geneticists. “These genes are involved in autism, absolutely,” says study investigator Steve Scherer, professor of medicine at the University of Toronto in Canada. “Those [genes] will become diagnostic tests for the autism screening panel.” The researchers looked at areas of the genome with tandem repeats — stretches of 2 to 20 nucleotides, which are the ‘building blocks’ of DNA, that are repeated two or more times in one spot. These repeats can expand when they are passed down from parents to children: If a nucleotide, or combination of them, is repeated 10 times in a parents’ DNA, it may be repeated hundreds of times in their child, for example. The more a repeat expands, the more likely it is that it will disrupt the gene’s function. Some specific repeats are already associated with autism: About 5 percent of autistic people have fragile X syndrome, which is nearly always caused by the expansion of a particular repeat in the FMR1 gene. But less than a quarter of people with autism have a known genetic cause, even though twin studies suggest that autism is highly heritable2. © 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: 27410 - Posted: 08.11.2020

by Peter Hess / Infants with particular patterns of electrical activity in the brain go on to have high levels of autism traits as toddlers, a new study shows1. Specifically, babies who have unusually high or low synchrony between certain brain waves — as measured by electroencephalography (EEG) — at 3 months old tend to score high on a standardized scale of autism-linked behaviors when they are 18 months old. These levels of synchrony reflect underlying patterns of connectivity in the brain. The findings suggest that EEG could help clinicians identify autistic babies long before these children show behaviors flagged by standard diagnostic tests. The work “reinforces the concept and the truism that brain development is affected before autism diagnoses are made,” says lead researcher Shafali Spurling Jeste, associate professor of psychiatry and neurology at the University of California, Los Angeles. “We believe that we could work to start rewiring the brain if we intervene effectively and early enough. That message, quite simply, is a very important one.” The study involved ‘baby sibs,’ the younger siblings of autistic children. Baby sibs are 10 to 20 times more likely to have autism than the general population. Previous research showed similar patterns of altered connectivity in functional magnetic resonance imaging (MRI) data from infants who were later diagnosed with autism, but MRI is costly and prone to errors. EEG measurements, on the other hand, are relatively inexpensive and simple to perform, which makes them more practical for clinical use, says Charles Nelson, professor of pediatrics and neuroscience at Harvard University, who was not involved in the study. © 2020 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 3: Neurophysiology: The Generation, Transmission, and Integration of Neural Signals
Related chapters from MM:Chapter 4: Development of the Brain; Chapter 2: Neurophysiology: The Generation, Transmission, and Integration of Neural Signals
Link ID: 27380 - Posted: 07.25.2020

by Angie Voyles Askham The autism gene SHANK3 is crucial for the development and function of muscles and the motor neurons that control them, according to a new study1. This relationship may explain why some people with mutations in the gene have low muscle tone, says co-lead investigator Maria Demestre, senior researcher at the Institute for Bioengineering of Catalonia in Barcelona. “It opens an avenue for treatment.” Between 1 and 2 percent of people with autism have a mutation in SHANK3. Deletions of the chromosomal region containing SHANK3 lead to Phelan-McDermid syndrome, characterized by intellectual disability, speech delay and, often, autism. One of the earliest signs of the syndrome in infants is hypotonia, or low muscle tone, which can result in difficulty feeding and a delay in reaching developmental milestones such as crawling and walking. SHANK3 encodes a protein that helps neurons communicate throughout the brain. But studies have shown that the gene is also found in other parts of the body and that mutations or deletions of genes in peripheral cells can contribute to autism traits2. SHANK3 is heavily expressed throughout the motor system of both mice and people, the new work shows. Muscle cells derived from people with Phelan-McDermid syndrome fail to mature, and mice deficient in SHANK3 have poor muscle function. The results add to “the growing appreciation of the role of autism-associated genes — in this case, SHANK3 — outside of the brain,” says David Ginty, professor of neurobiology at Harvard Medical School, who was not involved in the study. © 2020 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 4: Development of the Brain; Chapter 5: The Sensorimotor System
Link ID: 27375 - Posted: 07.21.2020

by Jonathan Moens / Autistic people with deletions in the chromosomal region 22q11.2 have a brain structure that’s distinct from that of autistic people without the deletions, according to a new brain imaging study1. The findings suggest that brain changes related to autism vary depending on the condition’s etiology, says study investigator Carrie Bearden, professor of clinical psychology at the University of California, Los Angeles. “[Autism is] really not one thing.” Deletions in 22q11.2 cause a syndrome characterized by heart defects, learning difficulties and an increased risk of psychiatric conditions such as schizophrenia. About 16 percent of people with the syndrome have autism2. Brain anatomy differs between people with the syndrome who have autism and those who do not, past studies by the same team show3. The new work is the first to compare these two groups with people who have ‘idiopathic’ autism, meaning its etiology is unknown. Disentangling these brain differences may be key to understanding if clinicians should treat autistic people with 22q deletions differently than people with autism without the deletions, Bearden says. “Maybe we’re treating these [conditions] as all the same at one level when we really need to dissect this a bit more.” Some experts say these findings could also be a first step toward dividing autism’s broad spectrum of traits into smaller sets of genetic conditions. © 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: 27372 - Posted: 07.18.2020