Autism Becomes a Focal Point at 2009 Society for Neuroscience Annual Meeting
With more than 30,000 scientists who study anything and everything having to do with the brain all convened inside a meeting center the size of multiple football fields, the annual Society for Neuroscience (SFN) meeting is like no other in the world. With thousands of science presentations going on
simultaneously each day, the 2009 SFN, held in Chicago on October 17-21, was a chance for autism to finally step into the spotlight. Although in past years autism has been highlighted in specific features of the meeting, this year autism science finally became one of the meeting focal points. Multiple sessions were devoted solely to autism spectrum disorders, placing the challenges and unique features of autism in front of tens of thousands of the world's best thinkers.
Although almost every aspect of autism and the brain was touched upon at the meeting, below are some of the many highlights and themes that emerged from the 2009 SFN meeting.*
Genes and Environmental Interactions in Brain Development
The causes of autism are likely multiple and include a complex combination of genetics and environmental factors. Thankfully, as shown at this year's meeting, researchers are beginning to tease apart the complex combinations of risk factors. In one session alone, Autism: Pharmacological and Environmental Models, thirty different presentations described environmental factors as varied as heavy metals, chlorination byproducts, pesticides, fatty acids, anticonvulsants and antidepressants, and their impact upon brain development.
One of the many unexplained features of autism is its gender-bias. For that reason, many investigators are searching for exposures that have especially detrimental effects on males. Researchers at Oklahoma State University investigated how exposure to metals interferes with the brain neurotransmitter dopamine. Using a very social animal species—the prairie vole—the investigators added metals to drinking water and showed decreases in dopamine signaling in conjunction with reduced social behavior toward strangers, and more time spent in isolation. Importantly, although male and female voles received the same dose of metals in their experiments, only the males were affected. Additionally, researchers from the New York Institute of Basic Research found that following prenatal exposure to high concentrations of water cholorination byproducts, only the male mice displayed defects in the three cardinal domains of autism impairment – social, communication, and stereotyped behaviors. Scientists from Stanford University also reported early postnatal oxygen deprivation appears to have gender-specific effects, with only male mice showing anatomical changes and later-developing social deficits.
Understanding how environmental exposures interact with the specific genetic makeup unique to each individual is a very difficult issue to untangle. By beginning to combine different types of risk factors, several groups at the meeting reported making progress in the investigation of such "gene/environment" interactions. Researchers from Massachusetts Institute of Technology and UC Los Angeles found that mice with defects in different autism related genes are especially sensitive to the effects of another candidate environmental factor, that being the activation of the maternal immune system during pregnancy. Following their presentation from last year, researchers from the University of Oklahoma have uncovered an unexpected connection between environmental stressors and genetic manipulation of the neuroligin gene, which regulates nerve cell communication in the brain. In their animal model, deleting the neuroligin gene was sufficient to generate oxidative stress and increase sensitivity to mercury. Finally, using blood samples from children with and without autism, researchers from UC Davis and the MIND Institute are investigating how individuals with autism react to heavy metals such as mercury or lead. They find that even though blood concentrations of mercury or lead may be the same as in controls, individuals with autism show very different correlations of gene expression in relation to their levels of either heavy metal. This evidence supports the hypothesis that environmental toxins may have different influences based upon the genetic background of each individual.
Oxytocin and Serotonin
Oxytocin is a hormone that plays a key role in mediating social affiliation. Several presentations at this year's meeting touched upon understanding how oxytocin may impact issues related to autism. Using a species often studied for their social bonding, a team of scientists from Ohio found that manipulating levels of oxytocin in newborn prairie voles changed their adult levels of serotonin, another chemical related to autism. Other researchers from the University of Milan in Italy are closely characterizing the defects in social recognition and memory present in mice that are missing the gene for the oxytocin receptor. Lastly, although perhaps not as well known, oxytocin signaling is also active in the gut. Researchers from Columbia University studied what happens in the gut epithelium when oxytocin receptors are activated and found that it interacts with a signaling cascade involving the molecule PTEN, which, interestingly, is also the source of much interest for its role in brain signaling and autism. Although preliminary, such studies have therapeutic implications for the health of gut epithelium.
Serotonin itself has long been suspected to play a part in generating autism. Increased blood levels of serotonin are one of the most common clinical findings in patients with autism, and serotonin signaling has been linked to autism through genetic studies as well. Building upon these findings, a group of scientists from Hamamatsu University in Japan are taking a broad approach to investigating the role of serotonin signaling in autism by using postmortem tissue to study what serotonin genes are dysregulated in the brain of individuals with autism. Many groups at the meeting presented data examining the impact of manipulating very specific aspects of serotonin signaling. In one of the most exciting new animal models being developed for autism, scientists at Vanderbilt have created a mouse that carries a rare form of the serotonin transporter gene found in individuals with autism, which allows them to characterize the biological impact of this genetic variant. In their preliminary studies, they reported both behavioral and pharmacological changes in these animals, demonstrating that a specific genetic change found in patients with autism has biological relevance.
Model Systems
One of the major themes of the meeting was the importance of having appropriate model systems for autism. Researchers use these models to better understand the biological issues at the core of autism, providing the knowledge that serves as the basis for therapeutic interventions. At this year's meeting scientists reported that stem cell models of autism are currently being developed, with several presentations focused on the ongoing characterization of autism animal models, including mice, rats, prairie voles, dogs and monkeys.
One of the newest models that achieved much attention is an unusual and fairly obscure strain of mice known as "BTBR." A team of researchers from the National Institute of Mental Health (NIMH) presented several posters documenting that these animals have abnormal social and repetitive behaviors. Utilizing a new test of mouse ultrasonic communication they developed, it was demonstrated that young BTBR mice emit less complex vocalizations, utilizing a much more limited repertoire of calls than other mice strains. In collaboration with researchers from UC San Francisco, the team is now searching for the genetic differences responsible for these unusual features of the BTBR mice.
Although mice are the typical animal model system of choice, among the more unusual autism model systems presented this year were dogs and rhesus macaques, both of which have a behavioral repetoire that is much more rich and human-like than that of mouse models. UC Davis scientists are proposing the study of dogs as a model of autism because breeds differ so considerably in their social abilities and also their ability to read human communication cues, such as the ability to follow someone pointing, a task that is specifically difficult for individuals with autism. Other groups have begun to study non-human primates. For instance, scientists at RIKEN Brain Sciences Institute in Japan stumbled across a rhesus monkey that displays several features autism. This particular animal had deficits in "mirror neuron" activity and had difficulty engaging in a turn-taking game. Interestingly, instead of looking to the partner monkey's hands and their button-pressing during the game as he was supposed to, the atypical animal directed his gaze to his partner's mouth, reminiscent of abnormal gaze patterns in autism.
When specific genes are known to be linked with autism, researchers can take advantage of the ability to manipulate mouse genes to create "transgenic" animals that model these genetic changes. Multiple sessions at this year's SFN focused exclusively on these types of animal models, ranging from models of genetic mutations found in individuals with 'idiopathic' autism, to models of the diseases Neurofibromatosis, Fragile X, Rett, Angelman, Tuberous Sclerosis and Timothy syndromes, all of which are associated clinically with autism. These studies allow researchers to illuminate the biological impact of the genetic alterations found in patients.
We know that the signs of autism become apparent early in life, and scientists are utilizing their animal models to hunt for the earliest biological processes that may go awry in autism. According to new research presented at the meeting, these may be revealing defects in some of the very first stages of brain formation. Scientists from Duke University examined the birth of brain cells in a mouse model of the chromosome 22q11 deletion syndrome that is associated with autism. They were able to identify and localize defects to very specific subpopulations of precursor cells in the developing brain. In extremely exciting news, scientists from Stanford University reported the generation of a mouse model replicating the specific genetic defect of Timothy Syndrome, a human disorder in which 80% of the individuals have autism. Their early characterization suggests that when the mice are still developing, they have increased brain cell proliferation and abnormal migration of the cells out into the newly-forming brain.
Because autism is associated with epilepsy, many researchers are examining their autism models for defects in the development and function of 'inhibitory interneurons' in the brain. These cells are responsible for keeping the excitatory activity of the brain in check by releasing a brain chemical known as GABA. Using autism postmortem tissue, researchers from Boston University reported finding evidence for decreased GABA signaling in certain brain regions, consistent with the hypothesis that in individuals with autism there may be an imbalance between inhibitory and excitatory signaling. Inhibitory interneurons come in many subtypes. By using animal models with genetic defects related to autism, researchers are able to examine the involvement of interneurons in greater depth, with several groups at the meeting reporting decreased numbers of specific classes of interneurons. Perhaps the most surprising new data regarding the importance of interneurons to autism came from researchers at Baylor University who used complicated new gene technologies to delete the Rett syndrome gene only in interneurons, leaving the gene functioning normally everywhere else. Remarkably, they found that this single genetic manipulation of a mouses' interneurons reproduced at the behavioral level many of the unusual social and repetitive behaviors that characterize Rett syndrome. This reveals that the GABA interneurons may play a vital role not only in related symptoms of autism such as epilepsy, but in the regulation of core features of autism spectrum disorders including social behavior.
Because several genes implicated in autism are known to participate in brain cell communication, many lectures and presentations focused on using animal models to closely study synapses, the site of cell-cell communication in the brain. In a major keynote address on the second day of the meeting, Tom Sudhof, M.D., from Stanford University, summarized what his team has learned from generating animal models of the neuroligin gene mutations found in rare individuals with autism. Neuroligins work together with their binding partners, the neurexins, to modulate the strength of synapses. Because both the neuroligins and neurexins come in multiple different forms, Dr. Sudhof and his collaborators are using mouse models to replicate the human autism mutations and understand their complicated biology. For example, mice with the neuroligin 3 gene mutation found in humans showed impaired social interactions but enhanced spatial learning abilities. On the other hand, deletion of the neurexin 1 gene, which has also been found associated with autism in several genetic screens, showed no effects on social behavior in mice but instead resulted in another feature of autism, increased repetitive behavior. Researchers hope that by building up an arsenal of neuroligin and neurexin mutant mice, they will understand neuroligin function and how changes in synaptic communication can affect people with autism.
Brain Circuitry and Networks
Proper synaptic connections between nerve cells is what allows the brain to form functional circuits. Therefore, another subject of multiple autism presentations was understanding how changes in nerve cell communication will, in turn, affect brain circuitry. One prominent theme that emerged from a special symposium on autism circuitry was the importance of the balance of excitatory and inhibitory signals that neurons send to each other. These signals need to be in perfect balance for proper circuit function. Preliminary evidence from multiple groups investigating the many autism mouse models suggests a change in the ratio of this excitatory and inhibitory transmission as well as potential delays in establishment of mature circuit function. As a result, other scientists are now focusing on testing whether brain circuits in animal models of autism show the normal ability to learn and change, a concept known as "brain plasticity."
At another autism-specific symposium, researchers reported what they have learned from studying human brain electrophysiology in individuals with autism. Interestingly, using a technology to read brain activity known as MEG, research groups from University of Utah and UC Irvine reported finding unusual patterns of brain activity both in individuals with autism and their unaffected first degree relatives. At UCLA, genetics experts teamed up with imaging experts to assess how functional brain connectivity might be used as an endophenotype that can be applied to interpret complex genetics. The research team found that individuals who carried a specific genetic "risk" allele for a synaptic protein (CNTNAP2) showed atypically increased frontal cortex activity and more functional connectivity during a specific task. These results suggest that by pairing the power of brain imaging with genetics, we can learn more about the functional effect of different autism risk alleles in different behavioral contexts.
Translational Research Reveals New Treatment Opportunities
Of course the most important endpoint for all of this research is the "translation" of our understanding of basic biology into the development of meaningful intervention approaches. Whereas previously it was believed that the symptoms of autism were fixed and untreatable, at this year's meeting a new attitude toward the potential of treatments for autism was reflected in the number of presentations concerning therapeutic approaches.
Difficulties with social interaction is a hallmark of autism spectrum disorders. However, it has not always been clear whether these deficits are due directly to impairments in sociability or instead to the anxiety generated by the prospect of social interactions. In an attempt to disentangle the social phenotype of autism from the issue of anxiety, researchers from the University of Pennsylvania used an anti-anxiety medication to treat a strain of mice with social defects. Through very careful behavioral testing, they found that although there were improved anxiety symptoms in the animals, the medication had no impact on their degree of social interaction. Similarly, researchers from New York Institute for Basic Research used an anti-depressant to treat a social defect in a different strain of mice, and found that while the medication worked to improve social interactions, it did not affect their anxiety behaviors, reiterating that social behavior is separable from anxiety behavior. The researchers hope this will help clarify the correct treatment approaches for the social endophenotype of autism.
Two years ago, using an animal model of Rett syndrome, researchers demonstrated that the neurological symptoms of Rett could be rescued, even in adult animals, galvanizing scientists across the world to search for treatment approaches for neurodevelopmental disorders. At this year's meeting, researchers from UC Los Angeles presented data demonstrating treatment of the mouse model of Tuberous Sclerosis was also possible, reversing neurological defects and improving survival rate. Two teams of researchers (from University of Alabama at Birmingham and the University of Illinois) showed that they could correct social behaviors and other neurological defects by treating animal models of Fragile X syndrome with lithium.
Most excitingly, the new focus on autism treatment has begun to extend beyond models of genetic disorders that share overlap with autism into the many new models of autism itself. Among the most unusual treatment-related presentations at the meeting, researchers from the National Institute of Mental Health used the BTBR mouse model of autism to test a "peer intervention" approach. The investigators found that housing adolescent BTBR mice together for three weeks with a group of highly social peer mice was sufficient to improve the previously asocial behavior of the BTBR mice. The researchers are currently pursing identification of the critical intervention components that mediated the improvement. Although preliminary, by demonstrating that the utility of autism model systems extends beyond pharmacological interventions and into the realm of developmental and behavioral interventions, yet another new avenue of autism research has been opened in 2009!
Although almost every aspect of autism and the brain was touched upon at the meeting, below are some of the many highlights and themes that emerged from the 2009 SFN meeting.*
Genes and Environmental Interactions in Brain Development
The causes of autism are likely multiple and include a complex combination of genetics and environmental factors. Thankfully, as shown at this year's meeting, researchers are beginning to tease apart the complex combinations of risk factors. In one session alone, Autism: Pharmacological and Environmental Models, thirty different presentations described environmental factors as varied as heavy metals, chlorination byproducts, pesticides, fatty acids, anticonvulsants and antidepressants, and their impact upon brain development.
One of the many unexplained features of autism is its gender-bias. For that reason, many investigators are searching for exposures that have especially detrimental effects on males. Researchers at Oklahoma State University investigated how exposure to metals interferes with the brain neurotransmitter dopamine. Using a very social animal species—the prairie vole—the investigators added metals to drinking water and showed decreases in dopamine signaling in conjunction with reduced social behavior toward strangers, and more time spent in isolation. Importantly, although male and female voles received the same dose of metals in their experiments, only the males were affected. Additionally, researchers from the New York Institute of Basic Research found that following prenatal exposure to high concentrations of water cholorination byproducts, only the male mice displayed defects in the three cardinal domains of autism impairment – social, communication, and stereotyped behaviors. Scientists from Stanford University also reported early postnatal oxygen deprivation appears to have gender-specific effects, with only male mice showing anatomical changes and later-developing social deficits.
Understanding how environmental exposures interact with the specific genetic makeup unique to each individual is a very difficult issue to untangle. By beginning to combine different types of risk factors, several groups at the meeting reported making progress in the investigation of such "gene/environment" interactions. Researchers from Massachusetts Institute of Technology and UC Los Angeles found that mice with defects in different autism related genes are especially sensitive to the effects of another candidate environmental factor, that being the activation of the maternal immune system during pregnancy. Following their presentation from last year, researchers from the University of Oklahoma have uncovered an unexpected connection between environmental stressors and genetic manipulation of the neuroligin gene, which regulates nerve cell communication in the brain. In their animal model, deleting the neuroligin gene was sufficient to generate oxidative stress and increase sensitivity to mercury. Finally, using blood samples from children with and without autism, researchers from UC Davis and the MIND Institute are investigating how individuals with autism react to heavy metals such as mercury or lead. They find that even though blood concentrations of mercury or lead may be the same as in controls, individuals with autism show very different correlations of gene expression in relation to their levels of either heavy metal. This evidence supports the hypothesis that environmental toxins may have different influences based upon the genetic background of each individual.
Oxytocin and Serotonin
Oxytocin is a hormone that plays a key role in mediating social affiliation. Several presentations at this year's meeting touched upon understanding how oxytocin may impact issues related to autism. Using a species often studied for their social bonding, a team of scientists from Ohio found that manipulating levels of oxytocin in newborn prairie voles changed their adult levels of serotonin, another chemical related to autism. Other researchers from the University of Milan in Italy are closely characterizing the defects in social recognition and memory present in mice that are missing the gene for the oxytocin receptor. Lastly, although perhaps not as well known, oxytocin signaling is also active in the gut. Researchers from Columbia University studied what happens in the gut epithelium when oxytocin receptors are activated and found that it interacts with a signaling cascade involving the molecule PTEN, which, interestingly, is also the source of much interest for its role in brain signaling and autism. Although preliminary, such studies have therapeutic implications for the health of gut epithelium.
Serotonin itself has long been suspected to play a part in generating autism. Increased blood levels of serotonin are one of the most common clinical findings in patients with autism, and serotonin signaling has been linked to autism through genetic studies as well. Building upon these findings, a group of scientists from Hamamatsu University in Japan are taking a broad approach to investigating the role of serotonin signaling in autism by using postmortem tissue to study what serotonin genes are dysregulated in the brain of individuals with autism. Many groups at the meeting presented data examining the impact of manipulating very specific aspects of serotonin signaling. In one of the most exciting new animal models being developed for autism, scientists at Vanderbilt have created a mouse that carries a rare form of the serotonin transporter gene found in individuals with autism, which allows them to characterize the biological impact of this genetic variant. In their preliminary studies, they reported both behavioral and pharmacological changes in these animals, demonstrating that a specific genetic change found in patients with autism has biological relevance.
Model Systems
One of the major themes of the meeting was the importance of having appropriate model systems for autism. Researchers use these models to better understand the biological issues at the core of autism, providing the knowledge that serves as the basis for therapeutic interventions. At this year's meeting scientists reported that stem cell models of autism are currently being developed, with several presentations focused on the ongoing characterization of autism animal models, including mice, rats, prairie voles, dogs and monkeys.
One of the newest models that achieved much attention is an unusual and fairly obscure strain of mice known as "BTBR." A team of researchers from the National Institute of Mental Health (NIMH) presented several posters documenting that these animals have abnormal social and repetitive behaviors. Utilizing a new test of mouse ultrasonic communication they developed, it was demonstrated that young BTBR mice emit less complex vocalizations, utilizing a much more limited repertoire of calls than other mice strains. In collaboration with researchers from UC San Francisco, the team is now searching for the genetic differences responsible for these unusual features of the BTBR mice.
Although mice are the typical animal model system of choice, among the more unusual autism model systems presented this year were dogs and rhesus macaques, both of which have a behavioral repetoire that is much more rich and human-like than that of mouse models. UC Davis scientists are proposing the study of dogs as a model of autism because breeds differ so considerably in their social abilities and also their ability to read human communication cues, such as the ability to follow someone pointing, a task that is specifically difficult for individuals with autism. Other groups have begun to study non-human primates. For instance, scientists at RIKEN Brain Sciences Institute in Japan stumbled across a rhesus monkey that displays several features autism. This particular animal had deficits in "mirror neuron" activity and had difficulty engaging in a turn-taking game. Interestingly, instead of looking to the partner monkey's hands and their button-pressing during the game as he was supposed to, the atypical animal directed his gaze to his partner's mouth, reminiscent of abnormal gaze patterns in autism.
When specific genes are known to be linked with autism, researchers can take advantage of the ability to manipulate mouse genes to create "transgenic" animals that model these genetic changes. Multiple sessions at this year's SFN focused exclusively on these types of animal models, ranging from models of genetic mutations found in individuals with 'idiopathic' autism, to models of the diseases Neurofibromatosis, Fragile X, Rett, Angelman, Tuberous Sclerosis and Timothy syndromes, all of which are associated clinically with autism. These studies allow researchers to illuminate the biological impact of the genetic alterations found in patients.
We know that the signs of autism become apparent early in life, and scientists are utilizing their animal models to hunt for the earliest biological processes that may go awry in autism. According to new research presented at the meeting, these may be revealing defects in some of the very first stages of brain formation. Scientists from Duke University examined the birth of brain cells in a mouse model of the chromosome 22q11 deletion syndrome that is associated with autism. They were able to identify and localize defects to very specific subpopulations of precursor cells in the developing brain. In extremely exciting news, scientists from Stanford University reported the generation of a mouse model replicating the specific genetic defect of Timothy Syndrome, a human disorder in which 80% of the individuals have autism. Their early characterization suggests that when the mice are still developing, they have increased brain cell proliferation and abnormal migration of the cells out into the newly-forming brain.
Because autism is associated with epilepsy, many researchers are examining their autism models for defects in the development and function of 'inhibitory interneurons' in the brain. These cells are responsible for keeping the excitatory activity of the brain in check by releasing a brain chemical known as GABA. Using autism postmortem tissue, researchers from Boston University reported finding evidence for decreased GABA signaling in certain brain regions, consistent with the hypothesis that in individuals with autism there may be an imbalance between inhibitory and excitatory signaling. Inhibitory interneurons come in many subtypes. By using animal models with genetic defects related to autism, researchers are able to examine the involvement of interneurons in greater depth, with several groups at the meeting reporting decreased numbers of specific classes of interneurons. Perhaps the most surprising new data regarding the importance of interneurons to autism came from researchers at Baylor University who used complicated new gene technologies to delete the Rett syndrome gene only in interneurons, leaving the gene functioning normally everywhere else. Remarkably, they found that this single genetic manipulation of a mouses' interneurons reproduced at the behavioral level many of the unusual social and repetitive behaviors that characterize Rett syndrome. This reveals that the GABA interneurons may play a vital role not only in related symptoms of autism such as epilepsy, but in the regulation of core features of autism spectrum disorders including social behavior.
Because several genes implicated in autism are known to participate in brain cell communication, many lectures and presentations focused on using animal models to closely study synapses, the site of cell-cell communication in the brain. In a major keynote address on the second day of the meeting, Tom Sudhof, M.D., from Stanford University, summarized what his team has learned from generating animal models of the neuroligin gene mutations found in rare individuals with autism. Neuroligins work together with their binding partners, the neurexins, to modulate the strength of synapses. Because both the neuroligins and neurexins come in multiple different forms, Dr. Sudhof and his collaborators are using mouse models to replicate the human autism mutations and understand their complicated biology. For example, mice with the neuroligin 3 gene mutation found in humans showed impaired social interactions but enhanced spatial learning abilities. On the other hand, deletion of the neurexin 1 gene, which has also been found associated with autism in several genetic screens, showed no effects on social behavior in mice but instead resulted in another feature of autism, increased repetitive behavior. Researchers hope that by building up an arsenal of neuroligin and neurexin mutant mice, they will understand neuroligin function and how changes in synaptic communication can affect people with autism.
Brain Circuitry and Networks
Proper synaptic connections between nerve cells is what allows the brain to form functional circuits. Therefore, another subject of multiple autism presentations was understanding how changes in nerve cell communication will, in turn, affect brain circuitry. One prominent theme that emerged from a special symposium on autism circuitry was the importance of the balance of excitatory and inhibitory signals that neurons send to each other. These signals need to be in perfect balance for proper circuit function. Preliminary evidence from multiple groups investigating the many autism mouse models suggests a change in the ratio of this excitatory and inhibitory transmission as well as potential delays in establishment of mature circuit function. As a result, other scientists are now focusing on testing whether brain circuits in animal models of autism show the normal ability to learn and change, a concept known as "brain plasticity."
At another autism-specific symposium, researchers reported what they have learned from studying human brain electrophysiology in individuals with autism. Interestingly, using a technology to read brain activity known as MEG, research groups from University of Utah and UC Irvine reported finding unusual patterns of brain activity both in individuals with autism and their unaffected first degree relatives. At UCLA, genetics experts teamed up with imaging experts to assess how functional brain connectivity might be used as an endophenotype that can be applied to interpret complex genetics. The research team found that individuals who carried a specific genetic "risk" allele for a synaptic protein (CNTNAP2) showed atypically increased frontal cortex activity and more functional connectivity during a specific task. These results suggest that by pairing the power of brain imaging with genetics, we can learn more about the functional effect of different autism risk alleles in different behavioral contexts.
Translational Research Reveals New Treatment Opportunities
Of course the most important endpoint for all of this research is the "translation" of our understanding of basic biology into the development of meaningful intervention approaches. Whereas previously it was believed that the symptoms of autism were fixed and untreatable, at this year's meeting a new attitude toward the potential of treatments for autism was reflected in the number of presentations concerning therapeutic approaches.
Difficulties with social interaction is a hallmark of autism spectrum disorders. However, it has not always been clear whether these deficits are due directly to impairments in sociability or instead to the anxiety generated by the prospect of social interactions. In an attempt to disentangle the social phenotype of autism from the issue of anxiety, researchers from the University of Pennsylvania used an anti-anxiety medication to treat a strain of mice with social defects. Through very careful behavioral testing, they found that although there were improved anxiety symptoms in the animals, the medication had no impact on their degree of social interaction. Similarly, researchers from New York Institute for Basic Research used an anti-depressant to treat a social defect in a different strain of mice, and found that while the medication worked to improve social interactions, it did not affect their anxiety behaviors, reiterating that social behavior is separable from anxiety behavior. The researchers hope this will help clarify the correct treatment approaches for the social endophenotype of autism.
Two years ago, using an animal model of Rett syndrome, researchers demonstrated that the neurological symptoms of Rett could be rescued, even in adult animals, galvanizing scientists across the world to search for treatment approaches for neurodevelopmental disorders. At this year's meeting, researchers from UC Los Angeles presented data demonstrating treatment of the mouse model of Tuberous Sclerosis was also possible, reversing neurological defects and improving survival rate. Two teams of researchers (from University of Alabama at Birmingham and the University of Illinois) showed that they could correct social behaviors and other neurological defects by treating animal models of Fragile X syndrome with lithium.
Most excitingly, the new focus on autism treatment has begun to extend beyond models of genetic disorders that share overlap with autism into the many new models of autism itself. Among the most unusual treatment-related presentations at the meeting, researchers from the National Institute of Mental Health used the BTBR mouse model of autism to test a "peer intervention" approach. The investigators found that housing adolescent BTBR mice together for three weeks with a group of highly social peer mice was sufficient to improve the previously asocial behavior of the BTBR mice. The researchers are currently pursing identification of the critical intervention components that mediated the improvement. Although preliminary, by demonstrating that the utility of autism model systems extends beyond pharmacological interventions and into the realm of developmental and behavioral interventions, yet another new avenue of autism research has been opened in 2009!
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