Posts tagged autism
Articles and news from the latest research reports.
Researcher adds to evidence linking autism to air pollutants
A researcher at the University of Wisconsin-Milwaukee (UWM) has added to a growing body of evidence that links autism to air pollutants such as those generated by cars and trucks.
Amy Kalkbrenner’s study, published this week online at the journal Epidemiology, showed that pollution’s impact on autism rates in North Carolina is similar to results of pollution-autism studies in California – despite weather and climate differences between the two states.
In addition, the work of Kalkbrenner and her colleagues, building on previous studies, showed that women in the third trimester of pregnancy were more susceptible to the damaging effects of air pollution on their unborn child.
“It adds another piece supporting the hypothesis that environmental chemicals are part of the autism puzzle,” says Kalkbrenner, an assistant professor in UWM’s Joseph J. Zilber School of Public Health. Autism, a spectrum of disorders affecting interpersonal relations and work achievement, now affects some 1 in 68 children in the U.S.
Her research team focused on exposure to coarse and fine particulate matter, known as PM10, which arises in part from traffic-related air pollution. The study evaluated records in the two states, covering pre-conception through the first birthday for 87,000 children in North Carolina and 77,500 in California born in the mid-to-late 1990s. Key regions in each state were selected based on researchers’ ability to simultaneously measure the level of particulate matter present, and know which children had autism in these regions.
Researchers used a new, more exact tool to measure the levels of particulate matter in smaller slices of time, based on pollution at the family’s address during pregnancy. With this method, they were able to compare exposures during specific weeks of pregnancy. The approximately one thousand children who later developed some form of autism spectrum disorders were then compared to all other children.
Kalkbrenner says it was important to look at eastern states because of the differences in climate, seasonal weather patterns and the chemical make-up of the particulate matter that might impact brain development. “Evidence for a link between a chemical exposure and a health impact like autism is stronger when it can be shown in more than one region.” The team found that the concentration of particulate matter was highest among children born in summer months in North Carolina and those born in fall and winter months in California.
Reasons for increased susceptibility in the third trimester of pregnancy are not known at this time. However, Kalkbrenner says this finding is consistent with theories that show links between autism and altered brain network development, specifically synaptic connections that are developing during the final months of pregnancy.
“We’ve now had three solid studies saying the same thing. The evidence is pretty compelling that something is going on with air pollution and autism,” says Kalkbrenner, who adds that further study is needed to determine the neurodevelopmental impacts of specific chemical pollutants during precise developmental windows.
(Source: www5.uwm.edu)
Chemical Derived from Broccoli Sprouts Shows Promise in Treating Autism
Results of a small clinical trial suggest that a chemical derived from broccoli sprouts — and best known for claims that it can help prevent certain cancers — may ease classic behavioral symptoms in those with autism spectrum disorders (ASDs).
The study, a joint effort by scientists at MassGeneral Hospital for Children and the Johns Hopkins University School of Medicine, involved 40 teenage boys and young men, ages 13 to 27, with moderate to severe autism.
In a report published online in the journal Proceedings of the National Academy of Sciences during the week of Oct. 13, the researchers say that many of those who received a daily dose of the chemical sulforaphane experienced substantial improvements in their social interaction and verbal communication, along with decreases in repetitive, ritualistic behaviors, compared to those who received a placebo.
“We believe that this may be preliminary evidence for the first treatment for autism that improves symptoms by apparently correcting some of the underlying cellular problems,” says Paul Talalay, M.D., professor of pharmacology and molecular sciences, who has researched these vegetable compounds for the past 25 years.
“We are far from being able to declare a victory over autism, but this gives us important insights into what might help,” says co-investigator Andrew Zimmerman, M.D., now a professor of pediatric neurology at UMass Memorial Medical Center.
Autism as a disorder of prediction
Autism is characterized by many different symptoms: difficulty interacting with others, repetitive behaviors, and hypersensitivity to sound and other stimuli. MIT neuroscientists have put forth a new hypothesis that accounts for these behaviors and may provide a neurological foundation for many of the disparate features of the disorder.
The researchers suggest that autism may be rooted in an impaired ability to predict events and other people’s actions. From the perspective of the autistic child, the world appears to be a “magical” rather than an orderly place, because events seem to occur randomly and unpredictably. In this view, autism symptoms such as repetitive behavior, and an insistence on a highly structured environment, are coping strategies to help deal with this unpredictable world.
The researchers hope that this unifying theory, if validated, could offer new strategies for treating autism.
“At the moment, the treatments that have been developed are driven by the end symptoms. We’re suggesting that the deeper problem is a predictive impairment problem, so we should directly address that ability,” says Pawan Sinha, an MIT professor of brain and cognitive sciences and the lead author of a paper describing the hypothesis in the Proceedings of the National Academy of Sciences this week.
“I don’t know what techniques would be most effective for improving predictive skills, but it would at least argue for the target of a therapy being predictive skills rather than other manifestations of autism,” he adds.
The paper’s senior author is Richard Held, a professor emeritus in the Department of Brain and Cognitive Sciences. Other authors are research affiliates Margaret Kjelgaard and Sidney Diamond, postdoc Tapan Gandhi, technical associates Kleovoulos Tsourides and Annie Cardinaux, and research scientist Dimitrios Pantazis.
Dealing with an unpredictable world
Sinha and his colleagues first began thinking about prediction skills as a possible underpinning for autism based on reports from parents that their autistic children insist on a very controlled, predictable environment.
“The need for sameness is one of the most uniform characteristics of autism,” Sinha says. “It’s a short step away from that description to think that the need for sameness is another way of saying that the child with autism needs a very predictable setting.”
Most people can routinely estimate the probabilities of certain events, such as other people’s likely behavior, or the trajectory of a ball in flight. The MIT team began to think that autistic children may not have the same computational abilities when it comes to prediction.
This hypothesized deficit could produce several of the most common autism symptoms. For example, repetitive behaviors and insistence on rigid structure have been shown to soothe anxiety produced by unpredictability, even in individuals without autism.
“These may be proactive attempts on the part of the person to try to impose some structure on an environment that otherwise seems chaotic,” Sinha says.
Impaired prediction skills would also help to explain why autistic children are often hypersensitive to sensory stimuli. Most people are able to become used to ongoing sensory stimuli such as background noises, because they can predict that the noise or other stimulus will probably continue, but autistic children have much more trouble habituating.
“If we were unable to habituate to stimuli, then the world would become overwhelming very quickly. It’s like you can’t escape this cacophony that’s falling on your ears or that you’re observing,” Sinha says.
Autistic children also often have a reduced ability to understand another person’s thoughts, feelings, and motivations — a skill known as “theory of mind.” The MIT team believes this could result from an inability to predict another person’s behavior based on past interactions. People with autism have difficulty using this type of context, and tend to interpret behavior based only on what is happening in that very moment.
Leonard Rappaport, chief of the division of developmental medicine at Boston Children’s Hospital, says he believes the new theory is “a uniting concept that could lead us to new approaches to understanding the etiology and perhaps lead to completely new treatment paradigms for this complex disorder.”
“This is not the first theory to explain the complex of symptoms we see every day in our clinical programs, but it seems to explain more of what we see than other theories that explain individual symptoms,” says Rappaport, who was not involved in the research.
Timing is everything
The researchers believe that different children may show different symptoms of autism based on the timing of the predictive impairment.
“In the millisecond range, you would expect to have more of an impairment in language,” Sinha says. “In the tens of milliseconds range, it might be more of a motor impairment, and in the range of seconds, you would expect to see more of a social and planning impairment.”
The hypothesis also predicts that some cognitive skills — those based more on rules than on prediction — should remain unharmed, or even be enhanced, in autistic individuals. This includes tasks such as math, drawing, and music, which are often strengths for autistic children.
A few previous studies have tried to pinpoint which parts of the brain are involved in making predictions. So far, the strongest candidates are the basal ganglia, the nucleus accumbens, and the cerebellum — structures that are often structurally abnormal in autistic patients. “It’s a very tentative connection at the moment, but I think this is a fruitful line of inquiry for the future,” Sinha says.
Sinha’s team has already begun testing some elements of the prediction-deficit hypothesis. Initial results of one study suggest that autistic children do have an impairment in habituation to sensory stimuli; in another set of experiments, the researchers are testing autistic children’s ability to track moving objects, such as a ball. “The hypothesis is guiding us toward very concrete studies,” Sinha says. “We hope to enlist the participation of families and children touched by autism to help put the theory through its paces.”
Study finds link between neural stem cell overgrowth and autism-like behavior in mice
People with autism spectrum disorder often experience a period of accelerated brain growth after birth. No one knows why, or whether the change is linked to any specific behavioral changes.
A new study by UCLA researchers demonstrates how, in pregnant mice, inflammation, a first line defense of the immune system, can trigger an excessive division of neural stem cells that can cause “overgrowth” in the offspring’s brain.
The paper appears Oct. 9 in the online edition of the journal Stem Cell Reports.
“We have now shown that one way maternal inflammation could result in larger brains and, ultimately, autistic behavior, is through the activation of the neural stem cells that reside in the brain of all developing and adult mammals,” said Dr. Harley Kornblum, the paper’s senior author and a director of the Neural Stem Cell Research Center at UCLA’s Semel Institute for Neuroscience and Human Behavior.
In the study, the researchers mimicked environmental factors that could activate the immune system — such as an infection or an autoimmune disorder — by injecting a pregnant mouse with a very low dose of lipopolysaccharide, a toxin found in E. coli bacteria. The researchers discovered the toxin caused an excessive production of neural stem cells and enlarged the offspring’s’ brains.
Neural stem cells become the major types of cells in the brain, including the neurons that process and transmit information and the glial cells that support and protect them.
Notably, the researchers found that mice with enlarged brains also displayed behaviors like those associated with autism in humans. For example, they were less likely to vocalize when they were separated from their mother as pups, were less likely to show interest in interacting with other mice, showed increased levels of anxiety and were more likely to engage in repetitive behaviors like excessive grooming.
Kornblum, who also is a professor of psychiatry, pharmacology and pediatrics at the David Geffen School of Medicine at UCLA, said there are many environmental factors that can activate a pregnant woman’s immune system.
“Although it’s known that maternal inflammation is a risk factor for some neurodevelopmental disorders such as autism, it’s not thought to directly cause them,” he said. He noted that autism is clearly a highly heritable disorder, but other, non-genetic factors clearly play a role.
The researchers also found evidence that the brain growth triggered by the immune reaction was even greater in mice with a specific genetic mutation — a lack of one copy of a tumor suppressor gene called phosphatase and tensin homolog, or PTEN. The PTEN protein normally helps prevent cells from growing and dividing too rapidly. In humans, having an abnormal version of the PTEN gene leads to very large head size or macrocephaly, a condition that also is associated with a high risk for autism.
“Autism is a complex group of disorders, with a variety of causes,” Kornblum said. “Our study shows a potential way that maternal inflammation could be one of those contributing factors, even if it is not solely responsible, through interactions with known risk factors.”
In addition, the team found that the proliferation of neural stem cell and brain overgrowth was stimulated by the activation of a specific molecular pathway. (A pathway is a series of actions among molecules within a cell that leads to a certain cell function.) This pathway involved the enzyme NADPH oxidase, which the UCLA researchers have previously found to be associated with neural stem cell growth.
“The discovery of these mechanisms has identified new therapeutic targets for common autism-associated risk factors,” said Janel Le Belle, an associate researcher in Kornblum’s lab and the paper’s lead author. “The molecular pathways that are involved in these processes are ones that can be manipulated and possibly even reversed pharmacologically.
“In agreement with past clinical findings, these data add to the significant evidence that autism-associated brain alterations begin prenatally and continue to evolve after birth,” she said.
Kornblum added that the findings that neural stem cell hyper-proliferation can contribute to autism-associated features may be somewhat surprising. “Autism neuropathology is primarily thought of as a dysregulation of neuronal connectivity, although the molecular and cellular means by which this occurs is not known,” he said. “Therefore, our hypothesis — that one potential means by which autism may develop is through an overproduction of cells in the brain, which then results in altered connectivity — is a new way of thinking about autism etiology.”
The next step, the researchers say, is to determine if and how the changes they observed lead to changes in the connections between brain cells, and if those effects can be altered after they have happened.
Multiple neurodevelopmental disorders have a common molecular cause
Neurodevelopmental disorders such as Down syndrome and autism-spectrum disorder can have profound, lifelong effects on learning and memory, but relatively little is known about the molecular pathways affected by these diseases. A study published by Cell Press October 9th in the American Journal of Human Genetics shows that neurodevelopmental disorders caused by distinct genetic mutations produce similar molecular effects in cells, suggesting that a one-size-fits-all therapeutic approach could be effective for conditions ranging from seizures to attention-deficit hyperactivity disorder.
"Neurodevelopmental disorders are rare, meaning trying to treat them is not efficient," says senior study author Carl Ernst of McGill University. "Once we fully define the major common pathways involved, targeting these pathways for treatment becomes a viable option that can affect the largest number of people."
A large fraction of neurodevelopmental disorders are associated with variation in specific genes, but the genetic factors responsible for these diseases are very complex. For example, whereas common variants in the same gene have been associated with two or more different disorders, mutations in many different genes can lead to similar diseases. As a result, it has not been clear whether genetic mutations that cause neurodevelopmental disorders affect distinct molecular pathways or converge on similar cellular functions.
To address this question, Ernst and his team used human fetal brain cells to study the molecular effects of reducing the activity of genes that are mutated in two distinct autism-spectrum disorders. Changes in transcription factor 4 (TCF4) cause 18q21 deletion syndrome, which is characterized by intellectual disability and psychiatric problems, and mutations in euchromatic histone methyltransferase 1 (EHMT1) cause similar symptoms in a disease known as 9q34 deletion syndrome.
Interfering with the activity of TCF4 or EHMT1 produced similar molecular effects in the cells. Strikingly, both of these genetic modifications resulted in molecular patterns that resemble those of cells that are differentiating, or converting from immature cells to more specialized cells. “Our study suggests that one fundamental cause of disease is that neural stem cells choose to become full brain cells too early,” Ernst says. “This could affect how they incorporate into cellular networks, for example, leading to the clinical symptoms that we see in kids with these diseases.”
(Image: Wellcome Images)
Presence or absence of early language delay alters anatomy of the brain in autism
A new study led by researchers from the University of Cambridge has found that a common characteristic of autism – language delay in early childhood – leaves a ‘signature’ in the brain. The results are published today (23 September) in the journal Cerebral Cortex.
The researchers studied 80 adult men with autism: 38 who had delayed language onset and 42 who did not. They found that language delay was associated with differences in brain volume in a number of key regions, including the temporal lobe, insula, ventral basal ganglia, which were all smaller in those with language delay; and in brainstem structures, which were larger in those with delayed language onset.
Additionally, they found that current language function is associated with a specific pattern of grey and white matter volume changes in some key brain regions, particularly temporal, frontal and cerebellar structures.
The Cambridge researchers, in collaboration with King’s College London and the University of Oxford, studied participants who were part of the MRC Autism Imaging Multicentre Study (AIMS).
Delayed language onset – defined as when a child’s first meaningful words occur after 24 months of age, or their first phrase occurs after 33 months of age – is seen in a subgroup of children with autism, and is one of the clearest features triggering an assessment for developmental delay in children, including an assessment of autism.
“Although people with autism share many features, they also have a number of key differences,” said Dr Meng-Chuan Lai of the Cambridge Autism Research Centre, and the paper’s lead author. “Language development and ability is one major source of variation within autism. This new study will help us understand the substantial variety within the umbrella category of ‘autism spectrum’. We need to move beyond investigating average differences in individuals with and without autism, and move towards identifying key dimensions of individual differences within the spectrum.”
He added: “This study shows how the brain in men with autism varies based on their early language development and their current language functioning. This suggests there are potentially long-lasting effects of delayed language onset on the brain in autism.”
Last year, the American Psychiatric Association removed Asperger Syndrome (Asperger’s Disorder) as a separate diagnosis from its diagnostic manual (DSM-5), and instead subsumed it within ‘autism spectrum disorder.’ The change was one of many controversial decisions in DSM-5, the main manual for diagnosing psychiatric conditions.
“This new study shows that a key feature of Asperger Syndrome, the absence of language delay, leaves a long lasting neurobiological signature in the brain,” said Professor Simon Baron-Cohen, senior author of the study. “Although we support the view that autism lies on a spectrum, subgroups based on developmental characteristics, such as Asperger Syndrome, warrant further study.”
“It is important to note that we found both differences and shared features in individuals with autism who had or had not experienced language delay,” said Dr Lai. “When asking: ‘Is autism a single spectrum or are there discrete subgroups?’ - the answer may be both.”
Brainwave Test Could Improve Autism Diagnosis and Classification
A new study by researchers at Albert Einstein College of Medicine of Yeshiva University suggests that measuring how fast the brain responds to sights and sounds could help in objectively classifying people on the autism spectrum and may help diagnose the condition earlier. The paper was published today in the online edition of the Journal of Autism and Developmental Disabilities.
The U.S. Centers for Disease Control and Prevention estimates that 1 in 68 children has been identified with an autism spectrum disorder (ASD). The signs and symptoms of ASD vary significantly from person to person, ranging from mild social and communication difficulties to profound cognitive impairments.
“One of the challenges in autism is that we don’t know how to classify patients into subgroups or even what those subgroups might be,” said study leader Sophie Molholm, Ph.D., associate professor in the Dominick P. Purpura Department of Neuroscience and the Muriel and Harold Block Faculty Scholar in Mental Illness in the department of pediatrics at Einstein. “This has greatly limited our understanding of the disorder and how to treat it.”
Autism is diagnosed based on a patient’s behavioral characteristics and symptoms. “These assessments can be highly subjective and require a tremendous amount of clinical expertise,” said Dr. Molholm. “We clearly need a more objective way to diagnose and classify this disorder.”
An earlier study by Dr. Molholm and colleagues suggested that brainwave electroencephalogram (EEG) recordings could potentially reveal how severely ASD individuals are affected. That study found that children with ASD process sensory information—such as sound, touch and vision—less rapidly than typically developing children do.
The current study was intended to see whether sensory processing varies along the autism spectrum. Forty-three ASD children aged 6 to 17 were presented with either a simple auditory tone, a visual image (red circle), or a tone combined with an image, and instructed to press a button as soon as possible after hearing the tone, seeing the image or seeing and hearing the two stimuli together. Continuous EEG recordings were made via 70 scalp electrodes to determine how fast the children’s brains were processing the stimuli.
The speed with which the subjects processed auditory signals strongly correlated with the severity of their symptoms: the more time required for an ASD individual to process the auditory signals, the more severe that person’s autistic symptoms. “This finding is in line with studies showing that, in people with ASD, the microarchitecture in the brain’s auditory center differs from that of typically developing children,” Dr. Molholm said.
The study also found a significant though weaker correlation between the speed of processing combined audio-visual signals and ASD severity. No link was observed between visual processing and ASD severity.
“This is a first step toward developing a biomarker of autism severity—an objective way to assess someone’s place on the ASD spectrum,” said Dr. Molholm. “Using EEG recordings in this way might also prove useful for objectively evaluating the effectiveness of ASD therapies.”
In addition, EEG recordings might help diagnose ASD earlier. “Early diagnosis allows for earlier treatment—which we know increases the likelihood of a better outcome,” said Dr. Molholm. “But currently, fewer than 15 percent of children with ASD are diagnosed before age 4. We might be able to adapt this technology to allow for early ASD detection and therapy for a much larger percentage of children.”
Researchers link gene to increased dendritic spines – a signpost of autism
Scientists at the UNC School of Medicine have discovered that knocking out the gene NrCAM leads to an increase of dendritic spines on excitatory pyramidal cells in the brains of mammals. Other studies have confirmed that the overabundance of dendritic spines on this type of brain cell allows for too many synaptic connections to form between neurons – a phenomenon strongly linked to autism.
(Image caption: A comparison of a dendrite with the protein NrCAM (top) and a dendrite without the protein (bottom), which has a greater density of spines that neurons use to form synaptic connections.)
The finding, published in The Journal of Neuroscience, adds evidence that NrCAM is a major player in neurological disorders. Previous UNC studies showed that knocking out the NrCAM gene caused mice to exhibit the same sorts of social behaviors associated with autism in humans.
“There are many genes involved in autism, but we’re now finding out exactly which ones and how they’re involved,” said Patricia Maness, PhD, professor of biochemistry and biophysics and senior author of the Journal of Neuroscience paper. “Knowing that NrCAM has this effect on dendrites allows us to test potential drugs, not only to observe a change in behaviors linked to autism but to see if we can improve dendritic spine abnormalities, which may underlie autism.
Maness’s finding comes on the heels of a report from Columbia University researchers who found an overabundance of the protein MTOR in mice bred to develop a rare form of autism. By using a drug to limit MTOR in mice, the Columbia researchers were able to decrease the number of dendritic spines and thus prune the overabundance of synaptic connections during adolescence. As a result, the social behaviors associated with autism were decreased. However, the drug used to limit MTOR can cause serious side effects, and it is located inside cells, making it a potentially difficult protein to target.
It is too early to tell if NrCAM and MTOR are linked, but Maness is now studying if the decreased amount of the NrCAM protein could trigger activation of MTOR. If so, then NrCAM, which is an accessible membrane-bound protein, might be a preferred therapeutic target for certain autism-related conditions.
In their study, Maness and her colleagues found that the NrCAM protein forms a complex with two other molecules to create a receptor on the membrane of excitatory pyramidal neurons. Maness’s team found that this receptor allows dendritic spines to retract, allowing for proper neuron pruning during maturation of the cortex. As a result, excitatory and inhibitory synapses between neurons develop in a balanced ratio necessary for brain circuits to function properly.
Maness, a member of the UNC Neuroscience Center and the Carolina Institute for Developmental Disabilities, also said that there are likely many other proteins downstream of NrCAM that depend on the protein to maintain the proper amount of dendritic spines. Decreasing NrCAM could allow for an increase in the levels of some of these proteins, thus kick starting the creation of dendritic spines.
“Basic science in autism is converging in really exciting ways,” Maness said. “Too many spines and too many excitatory connections that are not pruned between early childhood and adolescence could be one of the chief problems underlying autism. Our goal is to understand the molecular mechanisms involved in pruning and find promising targets for therapeutic agents.”
(Source: news.unchealthcare.org)
Size at birth affects risk of adolescent mental health disorders
New research from the Copenhagen Centre for Social Evolution and Yale University offers compelling support for the general evolutionary theory that birth weight and -length can partially predict the likelihood of being diagnosed with mental health disorders such as autism and schizophrenia later in life. The study analyzed medical records of 1.75 million Danish births, and subsequent hospital diagnoses for up to 30 years, and adjusted for almost all other known risk factors. The study is published today in the Proceedings of the Royal Society, London B.
The number of people diagnosed with mental health disorders is on the rise in most affluent countries, but we do not yet have a comprehensive understanding of the factors that make people vulnerable to these disorders.
A new analysis of the extensive Danish public health database suggests that part of the answer may reside in genetic imprints established at conception that influence both size at birth and mental health during childhood and early adolescence.
The study tests predictions of the evolutionary theory of genomic imprinting – the idea that during fetal development some genes inherited from the mother are expressed differently to those inherited from the father. The potential consequence of this asymmetry is that maternal and paternal genes in a fetus will not cooperate fully during this period, even though they subsequently have shared interests due to their lifetime commitment to the same body.
Opposite forces balance each other
The reason for the conflict is that some of the genes known to be expressed in the placenta and the brain carry imprints that affect resource provisioning of the unborn child. When such genes come from the father, they favor investment of more of the mother’s resources in the developing fetus, whereas the maternally-imprinted genes will normally compensate for such paternally-influenced manipulative effects to lessen the drain on maternal resources. These opposite forces balance each other in most pregnancies, with the result that most children are born with close to average length and weight and with a high likelihood of balanced mental health development.
Small deviations may well be favorable in human populations, when somewhat heavier babies are more likely to develop abstract talents and somewhat lighter babies above average social talents, for instance. However, this incurs the risk of increasing the frequency of autistic- and schizophrenic-spectrum disorders in the rare cases where imprinting imbalances are larger. The theory may explain why natural selection has not removed this portion of the burden of mental disease from our ancestors.
The new study tests these predictions and its results are remarkably consistent. They show that the change to the risk of developing mental disorders when born smaller or larger than average are relatively small, but very consistent, clearly diametrical, and part of the single continuum that the theory predicts.
“When we started this large scale analysis four years ago, we hoped to find evidence that genetic imprinting happens, but we did not expect that the results would match the predictions as consistently as we found”, explains Professor Jacobus Boomsma, Director of the Centre for Social Evolution, University of Copenhagen, who coordinated the work.
Boomsma adds: “Our study confirms that larger babies have a higher risk for incurring autism-spectrum diagnoses later in life and lower risk for schizophrenia-spectrum disorders. For example, Danish newborns are on average 52 cm long and being born at 54 cm increases the autism risk by 20%. However, these are relative risks and these disorders remain rare: in this example the absolute risk increases from 0.65% to 0.78%. Risk patterns are opposite in smaller newborns, who have higher risks for schizophrenia and lower risks for autism. Only for the smallest, prematurely-born babies does this diametric pattern disappear, because they have elevated risks for almost all disease categories”.
Evolutionary conflicts
Boomsma also underlines that focused genomic studies will be needed to find out which genes are involved and how they affect brain function: ”Our Centre’s main objective is to develop and test evolutionary theory about the ways in which gene-level conflicts can corrupt even the most sophisticated forms of naturally evolved cooperation. It is no surprise that humans are vulnerable to such deep evolutionary conflicts, as are other mammals, and it is both useful and interesting to be aware of this part of our biological heritage”, says Professor Boomsma.
(Source: science.ku.dk)
Tipping the Balance of Behavior
Humans with autism often show a reduced frequency of social interactions and an increased tendency to engage in repetitive solitary behaviors. Autism has also been linked to dysfunction of the amygdala, a brain structure involved in processing emotions. Now Caltech researchers have discovered antagonistic neuron populations in the mouse amygdala that control whether the animal engages in social behaviors or asocial repetitive self-grooming. This discovery may have implications for understanding neural circuit dysfunctions that underlie autism in humans.
This discovery, which is like a “seesaw circuit,” was led by postdoctoral scholar Weizhe Hong in the laboratory of David J. Anderson, the Seymour Benzer Professor of Biology at Caltech and an investigator with the Howard Hughes Medical Institute. The work was published online on September 11 in the journal Cell.
"We know that there is some hierarchy of behaviors, and they interact with each other because the animal can’t exhibit both social and asocial behaviors at the same time. In this study, we wanted to figure out how the brain does that," Anderson says.
Anderson and his colleagues discovered two intermingled but distinct populations of neurons in the amygdala, a part of the brain that is involved in innate social behaviors. One population promotes social behaviors, such as mating, fighting, or social grooming, while the other population controls repetitive self-grooming—an asocial behavior.
Interestingly, these two populations are distinguished according to the most fundamental subdivision of neuron subtypes in the brain: the “social neurons” are inhibitory neurons (which release the neurotransmitter GABA, or gamma-aminobutyric acid), while the “self-grooming neurons” are excitatory neurons (which release the neurotransmitter glutamate, an amino acid).
To study the relationship between these two cell types and their associated behaviors, the researchers used a technique called optogenetics. In optogenetics, neurons are genetically altered so that they express light-sensitive proteins from microbial organisms. Then, by shining a light on these modified neurons via a tiny fiber optic cable inserted into the brain, researchers can control the activity of the cells as well as their associated behaviors.
Using this optogenetic approach, Anderson’s team was able to selectively switch on the neurons associated with social behaviors and those linked with asocial behaviors.
With the social neurons, the behavior that was elicited depended upon the intensity of the light signal. That is, when high-intensity light was used, the mice became aggressive in the presence of an intruder mouse. When lower-intensity light was used, the mice no longer attacked, although they were still socially engaged with the intruder—either initiating mating behavior or attempting to engage in social grooming.
When the neurons associated with asocial behavior were turned on, the mouse began self-grooming behaviors such as paw licking and face grooming while completely ignoring all intruders. The self-grooming behavior was repetitive and lasted for minutes even after the light was turned off.
The researchers could also use the light-activated neurons to stop the mice from engaging in particular behaviors. For example, if a lone mouse began spontaneously self-grooming, the researchers could halt this behavior through the optogenetic activation of the social neurons. Once the light was turned off and the activation stopped, the mouse would return to its self-grooming behavior.
Surprisingly, these two groups of neurons appear to interfere with each other’s function: the activation of social neurons inhibits self-grooming behavior, while the activation of self-grooming neurons inhibits social behavior. Thus these two groups of neurons seem to function like a seesaw, one that controls whether mice interact with others or instead focus on themselves. It was completely unexpected that the two groups of neurons could be distinguished by whether they were excitatory or inhibitory. “If there was ever an experiment that ‘carves nature at its joints,’” says Anderson, “this is it.”
This seesaw circuit, Anderson and his colleagues say, may have some relevance to human behavioral disorders such as autism.
"In autism," Anderson says, "there is a decrease in social interactions, and there is often an increase in repetitive, sometimes asocial or self-oriented, behaviors"—a phenomenon known as perseveration. "Here, by stimulating a particular set of neurons, we are both inhibiting social interactions and promoting these perseverative, persistent behaviors."
Studies from other laboratories have shown that disruptions in genes implicated in autism show a similar decrease in social interaction and increase in repetitive self-grooming behavior in mice, Anderson says. However, the current study helps to provide a needed link between gene activity, brain activity, and social behaviors, “and if you don’t understand the circuitry, you are never going to understand how the gene mutation affects the behavior.” Going forward, he says, such a complete understanding will be necessary for the development of future therapies.
But could this concept ever actually be used to modify a human behavior?
"All of this is very far away, but if you found the right population of neurons, it might be possible to override the genetic component of a behavioral disorder like autism, by just changing the activity of the circuits—tipping the balance of the see-saw in the other direction," he says.