The causes of autism (Under construction!)
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The latest statements: April, 2011 ROBERT MACNEIL: As we've reported, autism now affects one American child in a 110. Last month, a committee convened by public health officials in Washington called it a national health emergency. The dramatic rise in official figures over the last decade has generated a surge of scientific research to find what is causing autism. Among the centers for such research is here, the University of California, DavisMIND Institute in Sacramento. Here and around the country, we've talked to leading researchers about where that effort now stands. Among them is the director of research at the MIND Institute, Dr. David Amaral, the director of research at the US Davis MIND Institute in Sacramento, CA DR. DAVID AMARAL: Well, I think we're close to finding several causes for autism. But there's -- I don't think there's going to be a single cause. ROBERT MACNEIL:The science director of theSimons Foundation in New York, Dr. Gerald Fishbach; Dr. Martha Herbert, asssistant Professor of Neurology at Harvard Medical School, a Pediatric Neurologist at the Massachusetts General Hospital in Boston, and Dr. Craig Newschaffer, professor of epidemiology and biostatistics at Drexel University in Philadelphia. First, I asked, how close are we to discovering the cause of autism? DR. GERALD FISHBACH: I think we're much closer now than we were five years ago. There's been a tremendous amount of new information and discoveries. But with any disorder as complicated, as multifaceted as autism, I'm reluctant to say how close. DR. DAVID AMARAL: Everything we know about autism is that there are multiple genes that confer risk. The children have various co-morbid problems. And everything we know looks like this is a multitude of disorders all under the umbrella that we call autism spectrum disorders. DR. CRAIG NEWSCHAFFER: To begin with, I think there probably is no cause of autism. We're probably talking about multiple causes. And I think we already have identified some causal components on the genetics front. But if I can interpret your question as complete understanding of all of these complex causes of autism, I think we're still quite a ways away. ROBERT MACNEIL: Some people we've talked to say we are on the verge of big discoveries. Others say we're just scratching the surface. Where do you think we are? DR. GERALD FISHBACH: I think we're scratching the surface of big discoveries. DR. MARTHA HERBERT: I think it's somewhere in between. At the brain level, I think in the last five years, we've figured out that there's a coordination problem of the different parts of the brain not hooking up in as synchronized of a fashion. The question for me is why is that happening? ROBERT MACNEIL:The autism puzzle is proving to be immensely complex. But I asked what hunches they have on where the answer will be found. DR. DAVID AMARAL: Clearly, 30 years ago, we didn't know any genes that conferred risk of autism. Now, we know that there's at least 20 or more that seem to be associated with autism. The interesting thing, though, is that any particular gene that you might find that is related to autism is only related to about 1 to 2 percent of the cases of autism. So there -- I think what's clear now is that there's not going be a single autism gene. But there are many, many. DR. GERALD FISHBACH: Well, I think many people feel that autism is a problem in communication between cells in the brain. Now that's saying an obvious truth. The brain is a communicating organ. We take in sensory information. We put out motor actions. And in between, there's the whole phenomena of perception, understanding and digestion of that information. It's the phenomenon of synaptic transmission. And my belief is we will find root causes of autism at particular synapses in the brain. DR. CRAIG NEWSCHAFFER: Well, I think it's going to be a combination of continued good work on the genetic side of things. I also believe, however, that there are going be causal components that are nonheritable genetics, things that we refer to as environmental causes, with a capital E, environment-encompassing lifestyle factors -- exposures, things of that nature. And those were, by the way, we're still at the very beginning stages. DR. MARTHA HERBERT: I don't think there's any one cause of autism. I would lay money that we will not find one thing. We certainly haven't found one gene; we're finding hundreds of genes. We're finding boutique genes. We're finding genes that kids have and the parents don't have -- their own parents. I think that there are a lot of things environmentally that are overwhelming our ability to cope, metabolically, that are overwhelming our immune system. And the synergy -- the collective impact of that is to deplete our protective systems. And I think that's what's causing autism. DR. CRAIG NEWSCHAFFER: But I think the emphasis on genetics probably has been correct, at least as we think about the unfolding of our understanding of what causes autism. And I think over time, we realized that in addition to these genetic components, there is room for and probably just cause for investigating the environmental. So we're swinging around. DR. GERALD FISHBACH: First, there's no question that autism is a genetic disorder. That does not mean the environment is not tremendously important, because it is also clear that the genetics are complex. We're looking at the Simons Foundation for what are called de novo mutations -- mutations that arise anew in the germ cells of one or the other parent, sperm or egg. Because it appears that these de novo mutations have a very big effect, a very profound effect. If you have the mutation, you have a great risk of developing autism. DR. MARTHA HERBERT: I think that what you have is, yes, definitely a question of toxics and toxics in our environment, that some of them act like our own molecules, like hormones, for example. That's called endocrine disruption. Some of them get confused with neurotransmitters. Some of them damage our cell membranes. Many, many of them damage our mitochondria, our energy factories in our cells. DR. CRAIG NEWSCHAFFER: Something that I think is important in thinking about these complex causes is thinking about the window of vulnerability. When are these causes most likely to act? And again, I believe that that prenatal, intrauterine period is going be very, very important. So things from maternal diet, infections that mothers may be exposed to in pregnancy, exogenous chemicals, chemicals in the environment that could be neuro-developmentally significant. All these are things -- I think these things are likely to play a role. How large, how small, I think, is yet to be determined. DR. GERALD FISHBACH: I don't think this is an either-or effort. The issue is ideas and hypotheses. The genetics will facilitate work on the environment. ROBERT MACNEIL: One issue science considered settled for years won't go away: the parental belief that vaccines cause autism. Public health officials have steadily maintained there is no valid, scientific evidence of such a connection; all epidemiological studies have proved negative. But now, bowing to public opinion, the body that sets priorities in autism research, The Inter Agency Coordinating Committee, has recommended studies to determine whether small subgroups might be more susceptible to environmental exposures, including vaccines. DR. GERALD FISHBACH: Despite many, many, many epidemiological studies, no evidence that current vaccines in their present form have triggered autism. There are two prevalent things going on here: vaccination and autism. But trying to correlate those two have failed to date. DR. DAVID AMARAL: So I think it's pretty clear that, in general, vaccines are not the culprit. If you look at children that receive the standard childhood vaccines. If anything those children are at are at slightly less risk of having autism than children that aren't immunized. It's not to say, however, that there is a small subset of children who may be particularly vulnerable to vaccines if the child was ill, if the child had a precondition, like a mitochondrial defect. Vaccinations for those children actually may be the environmental factor that tipped them over the edge of autism. And I think it's -- it is incredibly important still to try and figure out what, if any, vulnerabilities in a small subset of children might make them at risk for having certain vaccinations. DR. MARTHA HERBERT: I think it's possible that you could have a genetic subgroup. You also might have an immune subgroup. There are a variety of subgroups. But the problem with the population studies is they don't they aren't necessarily designed to have the statistical power to find subgroups like that if the subgroups are small. DR. DAVID AMARAL: I think more importantly what the whole vaccine issue has done is has opened our eyes again to the idea that the immune system is an important component of autism. DR. MARTHA HERBERT: The brain and the immune system and the gut are intimately related. The cells in those systems have common features. They work together seamlessly, and when you disregulate one, you disregulate all the others. And systems biology is a way of looking at how we work as an integrated whole. I think that's 21st century biology. Is the brain miswired, or is it misregulated? And I've come to think the brain is misregulated. And there are several reasons for that. Short-term, dramatic changes in the functional level of people with autism. One of them is the improvements you see with fever. A child who gets a fever will start to make eye contact, be interactive, will relate. A child who would have been really out of touch will become connected, and then it will go away. DR. DAVID AMARAL: You know, vaccines are only one of the things that we do to ourselves. But there are myriad other kinds of-- toxic chemicals that we're putting into the environment. I don't think there's enough research on environmental factors. Frankly, I think it's very expensive. It's difficult research to do. Because again, you start trying to develop a list of how many new things there are in the environment now, from 30 years ago. And it'll be a very long list. DR. MARTHA HERBERT: When we were having this explosion of our chemical revolution, we didn't have any way of knowing the subtle impacts on cellular function. We thought if it doesn't kill you, it's probably okay. But now we're learning that it can alter your regulation way before it kills you. ROBERT MACNEIL:There are many other areas of focus that researchers are pursuing. DR. GERALD FISHBACH: Parents are having children at later ages. And there is a lot of evidence that children born of parents in the late 30's and 40's have a higher likelihood of developing autism. DR. DAVID AMARAL: We're trying to chart the course of the -- of brain development in autism. And what we've found is that there are certain parts of the brain -- the frontal lobe, right behind the forehead, in particular -- as well as a small structure that's about two inches in from your ear, called the amygdala. Both of these structures actually grow too quickly. They get to the adult size too quickly in children with autism. There's a bunch of kids who probably have autism right from the get-go. Right-- you know, right from conception or -- very early on. There's another group of kids who, at 12 months old, they look fine. They're communicating, they're having -- engaging socially. But then sometime between 18 and 24 months, they lose social behavior. They lose language. And they regress back into autism. But now we're showing that the kids who regress into autism, for whatever reason, are the ones who have the rapidly growing brains. So that's a clue. I mean, it -- it doesn't tell us all that much. And it doesn't tell us how to treat those two kids differently, but it's beginning to provide evidence that there really are biologically different subsets of kids with autism. And I think once we actually define that there are different subsets, we can start going after the causes of each one of those subsets. ROBERT MACNEIL: Are you at all discouraged that after so much effort, investment, some of the best minds in the world on this, that -- that autism is still so baffling? DR. GERALD FISHBACH: I'm not discouraged at all about that. I think we're addressing one of the most profound problems in not only all of medicine but in all of human existence. We're talking about the ability to relate to other people, to empathize in a certain way and to comprehend. And I think it's the most worthwhile, most challenging effort in science that I've ever been involved in. So I'm not discouraged at all. According to Mary-Jane Schneider "...The evidence cited in the autism report included a major study done in Denmark, in which records of a half million children were analyzed. About one in five children had not received the vaccine, and the researchers found that these children developed autism at the same rate as children who had received the vaccine." From: "Introduction to Public Health", Page 146 But in the Denmark's study the ONLY one specific vaccine MMR (measles, mumps, and rubella) was analized. Nevertheless, usually kids are getting 21 shots by the time they are 4 years old and totally 41 shots by the time they are 9 years old. Therefore we have to review the practice (data) of Dr. Mayer Eisenstein from the Homefirst Health Services in metropolitan Chicago , where about 35,000 children have never been vaccinated. And they don’t have autism. The latest news: Protein found in brain cells may be key to autism Scientists have shown how a single protein may trigger autistic spectrum disorders by stopping effective communication between brain cells. The team from Duke University in North Carolina created autistic mice by mutating the gene which controls production of the protein, Shank3. The animals exhibited social problems, and repetitive behaviour - both classic signs of autism and related conditions. The Nature study raises hopes of the first effective drug treatments. Autism is a disorder which, to varying degrees, affects the ability of children and adults to communicate and interact socially. While hundreds of genes linked to the condition have been found, the precise combination of genetics, biochemistry and other environmental factors which produce autism is still unclear. Each patient has only one or a handful of those mutations, making it difficult to develop drugs to treat the disorder. Shank3 is found in the synapses - the junctions between brain cells (neurons) that allow them to communicate with each other. The researchers created mice which had a mutated form of Shank3, and found that these animals avoided social interactions with other mice. These findings and the mouse model now allow us to figure out the precise neural circuit defects responsible for these abnormal behaviours. They also engaged in repetitious and self-injurious grooming behaviour. Brain circuits When the MIT team analysed the animals' brains they found defects in the circuits that connect two different areas of the brain, the cortex and the striatum. Healthy connections between these areas are thought to be key to effective regulation of social behaviours and social interaction. The researchers say their work underscores just what an important role Shank3 plays in the establishment of circuits in the brain which underlie all our behaviours. Lead researcher Dr Guoping Feng said: "Our study demonstrated that Shank3 mutation in mice lead to defects in neuron-neuron communications. "These findings and the mouse model now allow us to figure out the precise neural circuit defects responsible for these abnormal behaviours, which could lead to novel strategies and targets for developing treatment." It is thought that only a small percentage of people with autism have mutations in Shank3, but Dr Feng believes many other cases may be linked to disruptions to other proteins that control synaptic function. If true he believes it should be possible to develop treatments that restore synaptic function, regardless of which protein is defective in a specific individual. Carol Povey, director of the National Autistic Society's Centre for Autism, said: "Animal research can help advance our understanding or the role of genetics and their influence on behaviour, however it is only a small part of the picture when it comes to understanding autism. "Human brains are far more complex than those of other mammals, and it is believed that a variety of factors are responsible for the development of the condition." http://www.bbc.co.uk/news/health-12759587 Autism Spectrum Disorder Linked To Genetic Synaptic Behaviors It seems that the place where your brain transfers electricity between synapses and how your genes determine how these processes function, are tied to autism in one way or another. There can be genetically driven disturbances in this process that lead to varying levels of autism according to a new study of DNA from approximately 1,000 autistic children and their kin. Peter S. White, a molecular geneticist and director of the Center for Biomedical Informatics stated: "This large study is the first to demonstrate a statistically significant connection between genomic variants in autism and both (nerve cell) synaptic function and neurotransmission." Entire collections of genes with similar neural roles which, taken as a group, seem to be associated with a greater proportion of autism risk. Searching for links between genetic irregularities and abnormal motor control and/or learning disabilities, the study focused on copy number variations (CNVs) that occur when the number of copies of a particular gene varies from one individual to the next. About 800 CNVs were identified as exclusive to autistic children. In addition, the CNVs in question tended to be found in genes central to the impaired biological functions that show up in autistic behavior including synapse function, nerve cell communication and brain development. White continues: "This suggested to us that there may be many different - possibly even hundreds - of genetic paths to autism, with only a few gene alterations relevant to each individual patient. But if those hundreds of genes have similar roles in the nervous system, the end result may lead to the same diagnosis: an autism spectrum disorder (ASD)." Different people with autism can have very different symptoms. Health care providers think of autism as a "spectrum" disorder, a group of disorders with similar features. One person may have mild symptoms, while another may have serious symptoms. But they both have an autism spectrum disorder. Ashley Scott-Van Zeeland, a postdoctoral research fellow at the Scripps Translational Science Institute in San Diego added: "What this study found is that there are perhaps many autisms. There may be a number of unique or very rare genetic mutations associated with the disorder. But this suggests that they follow a common pathway that leads to autism. So that could mean that instead of the old paradigm of finding one mutated gene or protein and then developing a drug targeting just for that, now we could look for entire pathways involved in autism. And then potentially we could intervene with those processes with new therapeutics." Currently autism therapies attempt to lessen the deficits and family distress associated with autism and other autism spectrum disorders , and to increase the quality of life and functional independence of autistic individuals, especially children. No single treatment is best, and treatment is typically tailored to the child's needs. Many medications are used to treat problems associated with ASD. More than half of U.S. children diagnosed with ASD are prescribed psychoactive drugs or anticonvulsants, with the most common drug classes being antidepressants, stimulants, and antipsychotics. Aside from antipsychotics, there is scant reliable research about the effectiveness or safety of drug treatments for adolescents and adults with ASD. A person with ASD may respond atypically to medications, the medications can have adverse effects, and no known medication relieves autism's core symptoms of social and communication impairments. Source: Molecular Psychiatry Written by Sy Kraft http://www.medicalnewstoday.com/articles/223122.php Groundbreaking Primate Study Links Mercury Vaccine Preservative To Brain Injury A new study in the leading scientific journal NeuroToxicology lends further credence to parents and scientists concerned about an increasingly aggressive childhood vaccine schedule and toxic vaccine components. A team led by researchers at the University of Pittsburgh found that infant macaque monkeys receiving a single Hepatitis B vaccine containing the mercury-based preservative thimerosal underwent significant delays in developing critical reflexes controlled by the brainstem. The infant macaques that did not receive vaccines developed normally. Government vaccine guidelines were expanded in 1991 to include a Hepatitis B vaccine for infants within the first few days of life, even though the disease is primarily transmitted sexually or spread through the use of dirty needles. The introduction of the shot was part of a greatly accelerated vaccine schedule that coincides with the drastic increase in autism, which now affects one in 100 American children. Thimerosal was removed from U.S. Hepatitis B vaccines in 2000 but was not recalled from the market and was administered for approximately two more years. It still remains in other vaccines including all multi-dose shots for both the seasonal flu and H1N1. Current government recommendations for seasonal flu and H1N1 call for pregnant women to receive both vaccines, and children as young as six months to receive as many as four separate flu shots. "This also doesn't take into account that nursing infants may be exposed to additional mercury through breastmilk should both mother and baby be vaccinated," says National Autism Association (NAA) board chair Lori McIlwain. "This study's outcome confirms that such an over-the-top toxic vaccine schedule is an assault on the developing brains of our children." Specifically, the study found: -- Thirteen newborn rhesus macaques were given a Hepatitis B vaccine containing a standardized dose of thimerosal adjusted for their weight, four received a saline placebo, and three were not given any shots. -- Vaccinated animals experienced a significant delay in the acquisition of three survival reflexes compared to unvaccinated animals. Root, snout, and suck reflexes, critical to animal survival in the wild, were delayed in the vaccinated macaques. -- These reflexes are controlled by the brainstem, a vital part of the brain that regulates automatic functions such as breathing, heart rate, and intestinal activity.v -- Neonatal responses in unvaccinated control animals were not delayed. -- The delay in acquisition of three of the four survival reflexes was not contingent on birth weight or gestational age. For years, parents of children with autism have lobbied government health agencies to conduct research comparing the health of vaccinated children to that of unvaccinated children, and to remove thimerosal from all vaccines. Neither request has been met. "This study underscores the lack of appropriate government action to ensure the safety of vaccines. Had our government agencies conducted the most basic research on the implications to children's health from the vaccines they rigorously promote, they could have spared thousands of children the neurological injuries they endure today," said Ms. McIlwain. "It's shameful." Source: National Autism Association http://www.medicalnewstoday.com/articles/166102.php |