by Giorgia Guglielmi Severe infections during early childhood are linked to autism — at least in some boys, a new study in mice and people suggests. The findings were published today in Science Advances. Researchers analyzed the health records of millions of children in the United States and found that boys diagnosed with autism are more likely than non-autistic boys to have had an infection requiring medical attention between age 1 and a half and 4. The study also showed that provoking a strong immune response in newborn mice with only one copy of TSC2, a gene tied to autism, leads to social memory problems in adult male rodents. In people, mutations in TSC2 cause tuberous sclerosis, a condition characterized by non-cancerous tumors and skin growths. About half of all people with tuberous sclerosis also have autism. “If the TSC2 mutation was sufficient to cause autism, then everyone with that mutation would have autism — but they don’t,” says senior investigator Alcino Silva, director of the Integrative Center for Learning and Memory at the University of California, Los Angeles. A child’s chances of having autism rise with severe infections in the child or his mother, previous studies show, but not all children who contract serious infections go on to be diagnosed with autism. The new study is the first to examine the relationship between immune activation and a specific genetic variant tied to autism, Silva says. The findings suggest that genetics and severe infection represent a ‘two-hit’ scenario for autism. © 2021 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 15: Emotions, Aggression, and Stress
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 11: Emotions, Aggression, and Stress
Link ID: 27996 - Posted: 09.18.2021

by Niko McCarty Brain scans from 16 mouse models of autism reveal at least four distinct patterns of brain activity, a new study suggests. The findings lend fresh support to the popular idea that autism is associated with a range of brain ‘signatures.’ Telltale neural signatures of autism have long proved elusive, with functional magnetic resonance imaging (fMRI) and other brain scanning technologies shouldering the blame for scattered and inconsistent results. “One big question is whether there’s a single signature of dysfunction in the brain of people with autism. And many people consider that to be, like, something that there must be,” says study investigator Alessandro Gozzi, senior researcher at the Istituto Italiano di Tecnologia in Rovereto, Italy. “If we’ve not found it yet, the blame must be on the method: fMRI.” The method gauges small changes in blood flow and oxygenation as an indirect measure of brain activity. For the new study, published in Molecular Psychiatry in August, Gozzi and his colleagues used fMRI to study brain connectivity patterns — or which brain regions ‘talk’ to each other, and to what degree. Brain regions are considered to be in communication if they have synchronous oscillations in blood flow. To tackle the question of reproducibility in fMRI, the researchers conducted their analysis in mice, anesthetizing the animals and fixing their heads in place to prevent any motion that could perturb brain signals. “We moved to a model organism where we can control, in exquisite detail, many of the factors that are considered to be at the basis of this variability, this unreliability in imaging,” Gozzi 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: 27982 - Posted: 09.11.2021

by Angie Voyles Askham Male mice exposed to atypically low levels of a placental hormone in the womb have altered brain development and asocial behaviors, according to a new study. The findings may help explain why preterm birth — which coincides with a deficiency in hormones made by the placenta — is linked to an increased likelihood of having autism. The hormone, called allopregnanolone, crosses the blood-brain barrier, binds to receptors for the chemical messenger gamma-aminobutyric acid (GABA) and helps regulate aspects of neurodevelopment, including the growth of new neurons. Its levels typically peak in the fetus during the second half of gestation. In the new study, researchers engineered a mouse model to have low fetal levels of allopregnanolone, mimicking the hormone’s loss due to preterm birth or placental dysfunction. The male mice in particular have structural changes in the cerebellum, a brain region known for balance and motor control, and exhibit more pronounced autism-like traits than control mice or female model mice. The new model “has a good translational potential for understanding the underlying mechanisms of sex differences in neurodevelopmental conditions such as autism,” says Amanda Kentner, professor of psychology at the Massachusetts College of Pharmacy and Health Sciences in Boston, who was not involved in the work. Injecting a pregnant mouse with allopregnanolone partway through gestation decreased the likelihood that its offspring would have autism-like traits, the researchers found. © 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: 27977 - Posted: 09.04.2021

by Peter Hess Some mutations in SCN2A, a gene reliably linked to autism, change social behaviors in mice by dampening the electrical activity of their neurons, according to a new study. SCN2A encodes a sodium channel that helps neurons send electrical signals. So-called ‘gain-of-function’ mutations make the channel hyperactive and can lead to epilepsy, whereas ‘loss-of-function’ mutations diminish its activity and are typically associated with autism. The mice in the new study carry the latter type and, as a result, have fewer functioning sodium channels than usual. The animals also react to unfamiliar mice in an atypical way, mirroring social behaviors seen in autistic people with similar SCN2A mutations. “We’re in the position of really connecting a single mutation, or at least a defect in the channel, to the behavior,” says lead investigator Geoffrey Pitt, professor of medicine at Weill Cornell Medicine in New York. “The message that our paper shows is that loss-of-function mutations and decreased sodium current can lead to behaviors.” This study confirms previous work showing that autism-linked mutations in SCN2A dampen channel activity in neurons, and further connects the loss-of-function mutations to clear changes in behavior, says Kevin Bender, associate professor of neurology at the University of California San Francisco, who was not involved in the work. “The behavioral results were actually some of the most robust that I’ve seen in this field to date.” © 2021 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 13: Memory and Learning; Chapter 3: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Link ID: 27968 - Posted: 08.28.2021

By Pamela Feliciano As social beings, when thinking about autism we tend to focus on its social challenges, such as difficulty communicating, making friends and showing empathy. I am a geneticist and the mother of a teenage boy with autism. I too worry most about whether he’ll have the conversational skills to do basic things like grocery shopping or whether he will ever have a real friend. But I assure you that the nonsocial features of autism are also front and center in our lives: intense insistence on sameness, atypical responses to sensory stimuli and a remarkable ability to detect small details. Many attempts have been made to explain all the symptoms of autism holistically, but no one theory has yet explained all the condition’s puzzling and diverse features. Now, a growing number of neurocognitive scientists think that many traits found in people with autism spectrum disorder (ASD) may be explained centrally by impairments in predictive skills—and have begun testing this hypothesis. Generally, the human brain determines what’s coming next based on the status quo, plus what we recall from previous experiences. Scientists theorize that people with ASD have differences that disturb their ability to predict. It’s not that people with autism can’t make predictions; it’s that their predictions are flawed because they perceive the world “too accurately.” Their predictions are less influenced by prior experiences and more influenced by what they are experiencing in the moment. They overemphasize the “now.” © 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: 27936 - Posted: 08.07.2021

by Peter Hess Neurons in mice with an autism-linked mutation sprout extraneous protrusions, an overgrowth that tracks with above-average motor learning. The animals lose both attributes when treated with an experimental drug that suppresses the activity of the Ras-ERK/MAPK cell signaling pathway, according to a new study. This pathway helps reshape neurons to change the strength of their connections in response to learning or other influences, part of a process known as neuroplasticity. “There is a balance between learning and forgetting in the brain,” says lead researcher Stelios Smirnakis, associate professor of neurology at Harvard University. “Understanding these pathways and how to balance them is of critical importance to a number of neurological disorders.” Hyperactivation of the Ras-ERK/MAPK pathway, which is also involved in cell growth, has been linked to cancer as well as multiple autism-related conditions. “A lot of genes in that pathway have been shown to underlie several forms of autism,” says Maria Chahrour, assistant professor of neuroscience at the University of Texas Southwestern Medical Center in Dallas, who was not involved in the study. “The pathway itself is also dysregulated in several forms of autism, so there’s a potential convergence.” The mice in the new work had an extra copy of the gene MECP2. As in previous studies and some other autism mouse models, the MECP2-duplication mice showed enhanced motor learning, mastering how to balance on a rotating rod more quickly than their wildtype counterparts. The animals’ motor learning prowess offers a model for studying how the repetitive behaviors seen in people with autism develop, the researchers say. © 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: 27918 - Posted: 07.21.2021

by Giorgia Guglielmi Autism research has long focused on genes involved in the formation of neurons and the function of synapses. Mutations in these genes were the first to be solidly linked to the condition and its traits. Over the past decade, however, several studies have implicated a second class of genes: those involved in the remodeling of chromatin — the complex of DNA and proteins that makes up chromosomes. These ‘chromatin regulators,’ which can influence whether other genes are turned on or off, are sometimes mutated in people with autism or other neurodevelopmental conditions. Scientists are just beginning to understand how these mutations can alter brain development. Why is chromatin remodeling important? If the chromosomes of a single human cell were stretched out and joined together end to end, their DNA would measure about 6.5 feet long. To fit inside a nucleus no wider than one-tenth of a human hair, the DNA strand wraps around histone proteins to form a series of bead-like structures called nucleosomes. Together these beads make up the chromatin. When a stretch of DNA is tightly packed into a nucleosome, it is inaccessible to the proteins that turn genes on and off by way of a process called transcription. For cells to express the right genes at the right time, their DNA needs to transition from tightly to loosely packed coils, a process carried out by a group of proteins called chromatin remodeling complexes. © 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: 27891 - Posted: 07.06.2021

by Niko McCarty Mutations in TSC2, a gene linked to autism and a related condition called tuberous sclerosis complex, cause developing neurons to ignore chemical cues that help them connect with each other, a new study suggests. The results may explain the altered wiring patterns seen in the brains of people with such mutations. TSC2 mutations disrupt the formation of axons, the long neuronal projections that send electrical signals from one brain cell to another, past research shows. Researchers long attributed this faulty wiring to problems with mTOR, a signaling pathway that helps neurons synthesize proteins and other materials they need to grow and form connections; without TSC2, mTOR runs amok. In neurons derived from the skin of a person with tuberous sclerosis, however, the mTOR pathway is not hyperactive, the new study found. Instead, the work implicates a different signaling protein: RhoA. “We were very surprised,” says Timothy Gómez, professor of neuroscience at the University of Wisconsin-Madison, who led the new study. “We were expecting this to be all mTOR.” RhoA helps neurons reshape an internal cytoskeleton as they extend axons toward other cells. Deletions or duplications of genes in the Rho pathway are found in people with autism. Several genes in the autism-linked chromosomal region 16p11.2 also interact with RhoA. “I’m glad to see that many autism-related genes are now converging on RhoA, which actually makes a lot of sense,” says Lilia Iakoucheva, associate professor of psychiatry at the University of California, San Diego, who was not involved in the study. “The work is beautiful.” © 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: 27880 - Posted: 06.29.2021

by Charles Q. Choi Mutations in CUL3, a leading autism gene, may disrupt the movements of neurons during development and interrupt the precise assembly of the brain, a new study suggests. Correcting this misdirection could lead to a therapy for autism in people with CUL3 mutations, the researchers say. Mutations that knock CUL3 out of commission are linked not only with autism, but also with varying levels of intellectual disability, movement problems, attention deficit hyperactivity disorder, epilepsy and sleep disturbances. Scientists have thoroughly explored how the protein that CUL3 encodes helps tag and break down other, expendable proteins in cells, but much remains unknown about its role in the developing brain. For the new work, researchers made mice that have only one functioning CUL3 gene instead of the usual two. These mice have movement problems, diminished sociability and poor memory — traits reminiscent of those in people with CUL3 mutations. The team also engineered mice in which they could knock out one copy of CUL3 by giving the rodents the cancer drug tamoxifen. Turning off CUL3 in 30-day-old juvenile mice had little effect, which suggests that CUL3 mutations contribute to autism-like behaviors during brain development, the researchers say. Identifying this window “is critical to consider for future critical trials,” says lead investigator Gaia Novarino, professor of neuroscience at the Institute of Science and Technology in Klosterneuburg, Austria. © 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: 27870 - Posted: 06.23.2021

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