Autism Spectrum Disorder: Uncovering Clues to a Complicated Condition

Autism Spectrum Disorder Uncovering Clues to a Complicated Condition Autism is a complex brain disorder that first appears during early childhood. It affects how a person behaves and interacts with others. People with autism might not look you in the eye when talking. They may spend a lot of time lining up toys or other objects. Or they may say the same sentence over and over. The disorder is so variable—affecting each person in very different ways—that it can be difficult to diagnose and treat. This variability is why autism is called a “spectrum” disorder. It spans the spectrum from mild to severe and includes a wide range of symptoms. NIH-funded scientists have been working to uncover the secrets of autism. They’ve identified genes that may boost the risk for autism. They’ve developed therapies that can help many of those affected. And they’ve found that starting treatment as early as possible can lead to better outcomes. Still, there’s much more we need to learn about this complicated condition. About 1 in 88 children may have autism spectrum disorder, according to the U.S. Centers for Disease Control and Prevention. The number of affected children has been growing in recent years. Many researchers believe this increase is due to better diagnosis and awareness. Others suspect that yet-unknown factors may be partly to blame. Although the exact causes of autism are unclear, research suggests that both genes and the environment play important roles. Autism affects a child’s development in different ways, and so it’s known as a developmental disorder. Parents are often the first to suspect that something may not be quite right with their child’s development. They may notice their baby doesn’t make eye contact, becomes overly focused on certain objects or isn’t “babbling” like other children the same age. “A parent may first have concerns when a child is under 2 years of age,” says Dr. Connie Kasari, a child development expert at the University of California, Los Angeles. “A more certain diagnosis can usually be made by age 2, but some cases might not be clear until much later.” There are no direct tests, like blood tests or brain scans, that can identify autism. Instead, the condition is diagnosed by looking at a child’s behaviors and development. “All affected children have some sort of social impairment, but symptoms vary along a continuum,” Kasari says. “Impairment can range from kids who are in their ‘own world’ and seemingly unaware of others to high-functioning individuals who are just awkward and seem to miss the point of social interactions.” In May 2013, the American Psychiatric Association updated an important book that’s used to diagnose and classify mental disorders. The DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) includes an updated definition for autism spectrum disorder. The condition is now identified by looking for 2 broad categories of symptoms: problems with social communication and the presence of “stereotyped” behaviors, such as walking in certain patterns or insisting on specific or unusual routines. To be diagnosed with autism, these symptoms must arise during early childhood, even if they’re not noticed until later, when social demands increase. “The new DSM-5 definition moves all the disorders into a single spectrum, rather than the 4 separate autistic disorders described in the past,” says NIH pediatrician and neuroscientist Dr. Susan Swedo. She chaired the expert panel that updated the DSM-5 definition of autism spectrum disorders. “The new criteria are also more inclusive of minorities, adolescents and young adults with autism than the previous edition, which focused more on boys ages 4 to 9.” Getting diagnosed as early as possible is crucial. “Autism is treatable even though it’s not curable,” says Dr. David Mandell, an expert in autism and health services at the University of Pennsylvania. “If we intervene early enough with appropriate and intensive care, we can reduce a lot of impairments for many kids who have autism.” Research has shown that therapies focusing on behavior and communication can be helpful. Some drugs can also reduce certain related symptoms, but no medications have been approved by the U.S. Food and Drug Administration specifically for treating the main symptoms of autism. “Because autism is such a complicated disorder, no one therapy fits everyone,” Kasari explains. Kasari and her colleagues developed and tested several treatments that focus on improving social skills and communication. In one study, preschoolers with autism received intense training in basic skills such as playing and sharing attention. Five years later, these children tended to have stronger vocabularies and better communication skills than children who received standard therapy. “We’ve found that if we can improve these basic skills, we can also improve language learning for these kids,” Kasari says. “We’re now studying 2 potential therapies in at-risk babies, ages 12- to 21-months old, to see if we can push language development along faster for the children.” Scientists are also looking for ways to predict likely outcomes for children with autism. One NIH-funded team found that the brain waves of some 2-year-olds with autism can have a distinctive pattern when they listen to familiar words. The children with more severe social symptoms didn’t have a typical focused response in the brain region that processes language. Follow-up studies showed that these brain responses predicted the children’s developmental abilities 2 and 4 years later. “In the future, we’d like to be able to assess a child based on brain function or their genetic profile and then identify the intervention that might be best for that particular kid,” Mandell says. A growing number of studies are looking at autism in older age groups. “While we think about autism as a disorder of childhood, it actually continues through adolescence and into adulthood,” Mandell says. “Some adults with autism have been misdiagnosed, and they can find themselves being treated for other conditions. We’d like to develop better screening tools and ultimately provide these adults with skills and supports to help them become happy and productive citizens.” While research is ongoing, it’s clear that early diagnosis and treatment can improve outcomes for those with autism. If you’re concerned about your child’s social communication and behaviors, don’t wait. Talk with your child’s doctor. You may be referred to a specialist who can do a thorough evaluation. The earlier autism is diagnosed, the sooner specific therapy can begin Social Worker Continuing Education

Aging and gene expression -- possible links to autism and schizophrenia in offspring

Advanced paternal age has been associated with greater risk for psychiatric disorders, such as schizophrenia and autism. With an increase in paternal age, there is a greater frequency of certain types of mutations that contribute to these disorders in offspring. Mutations are changes in the genetic code. Recent research, however, looks beyond the genetic code to "epigenetic effects", which do not involve changes in the genes themselves, but rather in how they are expressed to determine one's characteristics. Such epigenetic changes in sperm, related to ageing, have been linked with psychiatric disorders in offspring. Maria Milekic, PhD, reported today, at the American College of Neuropsychopharmacology annual meeting in Hollywood Florida, that old mice have an epigenetic change ‒ a loss of DNA methylation at the locations where the genetic code starts being transcribed. DNA methylation is a biochemical process that plays an important regulatory role in development and disease. The work was done by a research team in the Department of Psychiatry at Columbia University. Offspring of old fathers showed the same deficit in DNA methylation, and they differed in their behavior from the offspring of the young fathers. They showed less exploratory activity and differed in the startle response and in habituation. Two groups, with 10 breeder mice per group, were tested. The breeders were either old (12 month) or young (3 month) males, each bred with two young (3 month) female mice. Then the behavior of the offspring was tested when they were 3 months old. DNA methylation also was tested in the young and old fathers' sperm, and brains of the offspring were tested for DNA methylation as well as gene expression. "We were interested in understanding the mechanism of the paternal age effect", said Dr. Milekic."The risk for schizophrenia increases 2-fold when a father is over 45 years of age, and the risk for autism increases 2-5-fold. It seemed unlikely that mutation alone could account for this. We therefore speculated that DNA methylation could provide an alternative mechanism." Not only did the offspring of the old fathers differ from their counterparts with young fathers in DNA methylation, they also showed significant differences in the expression of genes that have been implicated in autism spectrum disorders and that are known to regulate the development and function of the brain. These findings point to possible factors that can lead to autism spectrum disorders and schizophrenia, and ultimately may lead to more effective therapeutic interventions. With respect to studies in the immediate future, Dr. Milekic said,"We are trying to evaluate changes in different brain regions. Our studies before did not compare brain regions. Most of the genes that have altered expression are in the cerebellum. We are interested in how DNA methylation in the cerebellum is affected by paternal age." Social Worker CEUs ### The work was supported by grants from NIMH and the Simon Foundation to Jay Gingrich, MD, PhD, and a NARSAD Young Investigator Awa rd from the Brain and Behavior Research Foundation to Dr. Milekic.

Focusing on faces

Researchers find neurons in amygdala of autistic individuals have reduced sensitivity to eye region of others' faces Difficulties in social interaction are considered to be one of the behavioral hallmarks of autism spectrum disorders (ASDs). Previous studies have shown these difficulties to be related to differences in how the brains of autistic individuals process sensory information about faces. Now, a group of researchers led by California Institute of Technology (Caltech) neuroscientist Ralph Adolphs has made the first recordings of the firings of single neurons in the brains of autistic individuals, and has found specific neurons in a region called the amygdala that show reduced processing of the eye region of faces. Furthermore, the study found that these same neurons responded more to mouths than did the neurons seen in the control-group individuals. "We found that single brain cells in the amygdala of people with autism respond differently to faces in a way that explains many prior behavioral observations," says Adolphs, Bren Professor of Psychology and Neuroscience and professor of biology at Caltech and coauthor of a study in the November 20 issue of Neuron that outlines the team's findings. "We believe this shows that abnormal functioning in the amygdala is a reason that people with autism process faces abnormally." The amygdala has long been known to be important for the processing of emotional reactions. To make recordings from this part of the brain, Adolphs and lead author Ueli Rutishauser, assistant professor in the departments of neurosurgery and neurology at Cedars-Sinai Medical Center and visiting associate in biology at Caltech, teamed up with Adam Mamelak, professor of neurosurgery and director of functional neurosurgery at Cedars-Sinai, and neurosurgeon Ian Ross at Huntington Memorial Hospital in Pasadena, California, to recruit patients with epilepsy who had electrodes implanted in their medial temporal lobes—the area of the brain where the amygdala is located—to help identify the origin of their seizures. Epileptic seizures are caused by a burst of abnormal electric activity in the brain, which the electrodes are designed to detect. It turns out that epilepsy and ASD sometimes go together, and so the researchers were able to identify two of the epilepsy patients who also had a diagnosis of ASD. By using the implanted electrodes to record the firings of individual neurons, the researchers were able to observe activity as participants looked at images of different facial regions, and then correlate the neuronal responses with the pictures. In the control group of epilepsy patients without autism, the neurons responded most strongly to the eye region of the face, whereas in the two ASD patients, the neurons responded most strongly to the mouth region. Moreover, the effect was present in only a specific subset of the neurons. In contrast, a different set of neurons showed the same response in both groups when whole faces were shown. "It was surprising to find such clear abnormalities at the level of single cells," explains Rutishauser. "We, like many others, had thought that the neurological abnormalities that contribute to autism were spread throughout the brain, and that it would be difficult to find highly specific correlates. Not only did we find highly specific abnormalities in single-cell responses, but only a certain subset of cells responded that way, while another set showed typical responses to faces. This specificity of these cell populations was surprising and is, in a way, very good news, because it suggests the existence of specific mechanisms for autism that we can potentially trace back to their genetic and environmental causes, and that one could imagine manipulating for targeted treatment." "We can now ask how these cells change their responses with treatments, how they correspond to similar cell populations in animal models of autism, and what genes this particular population of cells expresses," adds Adolphs. To validate their results, the researchers hope to identify and test additional subjects, which is a challenge because it is very hard to find people with autism who also have epilepsy and who have been implanted with electrodes in the amygdala for single-cell recordings, says Adolphs. "At the same time, we should think about how to change the responses of these neurons, and see if those modifications correlate with behavioral changes," he says MHC Continuing Education ### Funding for the research outlined in the Neuron paper, titled "Single-neuron correlates of abnormal face processing in autism," was provided by the Simons Foundation, the Gordon and Betty Moore Foundation, the Cedars-Sinai Medical Center, Autism Speaks, and the National Institute of Mental Health. Additional coauthors were Caltech postdoctoral scholar Oana Tudusciuc and graduate student Shuo Wang.

Autism Risk Unrelated to Total Vaccine Exposure in Early Childhood

A child’s risk for developing an autism spectrum disorder (ASD) is not increased by receiving “too many vaccines too soon,” according to a new study published in The Journal of Pediatrics. Although previous scientific evidence has shown that vaccines do not cause autism, more than 1 in 10 parents refuse or delay vaccinations for their young children. A main safety concern of these parents is the number of vaccines administered, both on a single day and over the course of a child’s first 2 years of life. In the first study of its kind, researchers from the CDC and Abt Associates, Inc. compared vaccine records for over 1000 children born from 1994–1999, some of whom were later diagnosed with ASD. The researchers calculated the total number of vaccine antigens each child received between birth and age 2, as well as the maximum number of antigens each child received on a single day. The study found that the total number of vaccine antigens received was the same between children with ASD and those without ASD. Additionally, antigen number was also found to be unrelated to the development of two sub-categories of ASD—autistic disorder and ASD with regression LCSW Continuing Education The researchers concluded, “The possibility that immunological stimulation from vaccines during the first 1 or 2 years of life could be related to the development of ASD is not well-supported by what is known about the neurobiology of ASDs.”