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Tero Toivanen

Research on the genomics of autism from the Center for Biom - 0 views

  • Research on the genomics of autism from the Center for Biomedical Informatics at The Childrens Hospital of Philadelphia indicated that several genes and genomic variants contribute to autism. The gene alterations are rare but when they are in play, they seem to disrupt genes that are significantly involved in brain development and nerve signaling.
  • According to the September 15, 2010 issue of Science Translational Medicine, males with certain DNA alterations to their X-chromosome are at high risk of having autism.
  • This research was performed at the Centre for Addiction and Mental Health (CAMH) and The Hospital for Sick Children (SickKids), in Toronto Canada.
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  • One percent of boys with autism involved in the study had mutations in the PTCHD1 gene on the X-chromosome. No boys without autism showed this mutation.
  • Girls who also had this mutation did not seem to exhibit autistic traits. It appears that girls may be protected from developing autism because they have a second X-chromosome.
  • Still these girls could be carriers, passing on the mutation to their children. Their sons could then have autism.
  • Certain rare genetic variants were found 20 percent more in children with autism than in other children. Researchers also discovered new disruptions, where a child of non-autistic parents had autism.
  • t appears that some children have private genetic mutations not passed on genetically, and this leaves them more susceptible to autism. Interestingly, each child showed a different disturbance in a different gene.
  • Researchers hope to gain more information as they identify groups of disrupted genes. Ultimately they hope to be able to develop treatments for autism.
Tero Toivanen

Auditory Integration Training and Facilitated Communication for Autism -- Committee on ... - 0 views

  • For example, Smith et al16 studied 10 individuals with autism specifically to investigate the effects of facilitator influence and level of assistance on the results of FC. Each subject had six sessions, two with no help, two with partial assistance, and two with full assistance. Results showed that there were no cases of correct responses from the subject unless the facilitator knew the correct response. In addition, numerous responses were typed by the subjects to stimuli that were shown only to the facilitator, and not the subject. Similar results have been found by Regal et al17 and Eberlin et al.1
  • One complication of the use of FC has been the allegation of abuse, particularly sexual abuse, that has been obtained from individuals through the use of FC against third persons. This has generated adverse publicity and caused severely negative consequences for families who may be unsure of the validity of the allegations. Because of legal mandates regarding reports of child abuse, this becomes a critical issue for teachers and pediatricians alike, who may find the credibility of the report highly questionable but are obligated to fulfill their legal responsibilities. Margolin20 notes that although more than 50 such allegations have resulted in legal proceedings, most have terminated before trial. The ethical dilemmas posed by FC for practitioners have been reviewed by Jacobson et al.8
  • It is important for the pediatrician to obtain current data on both AIT and FC as they become available. Until further information is available, the use of these treatments does not appear warranted at this time, except within research protocols.
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    This statement reviews the basis for two new therapies for autism---auditory integration training and facilitative communication. Both therapies seek to improve communication skills. Currently available information does not support the claims of proponents that these treatments are efficacious. Their use does not appear warranted at this time, except within research protocols.
Tero Toivanen

NeuroLogica Blog » The Genetics of Autism - 0 views

  • What this means is that there is likely to be a complex set of many factors that contribute to ASD - not one single cause.
  • The same exact situation is true for other entities, like schizophrenia and attention deficit disorder (ADD).
  • One difference, however, is that schizophrenia and ADD likely represent changes to particular parts of the brain, while autism is likely due to changes in the global architecture of the brain.
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  • Getting back to the genetics of autism, current models are therefore consistent with what is being found when the genetics of autism is researched - researchers are finding many genes that predispose to autism in a subset of cases but no single or simple universal cause. At present, 133 different gene variants have been linked to autism.
  • This new research, conducted by Dr. Hakon Hakonarson of the Children’s Hospital of Philadelphia, is a genome wide analysis involving about 10,000 individuals.
  • The results are especially significant because the variants lie between two genes, called CDH9 and CDH10, which are known to play an important role in forming nerve connections in the brain.
  • The gene variants that correlated with ASD are for proteins that are involved in the process of neurons forming connections with each other. There is already other lines of evidence that suggest what is different in ASD brains is a decrease in the amount of interconnectedness and communication among neurons. It is therefore likely no coincidence that this study found genetic correlations for proteins involved with neuronal connections.
  • This also is compatible with the finding that many separate genes are potentially involved with ASD - for there are many separate genes and processes involved with forming and maintaining neuronal connections.
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    A new genome-wide analysis of families with autism has found significant gene associations, adding to the growing evidence for strong genetic contribution to autism.
Tero Toivanen

New Theory Of Autism Suggests Symptoms Or Disorder May Be Reversible - 0 views

  • the brains of people with autism are structurally normal but dysregulated, meaning symptoms of the disorder might be reversible.
  • autism is a developmental disorder caused by impaired regulation of the locus coeruleus, a bundle of neurons in the brain stem that processes sensory signals from all areas of the body.
  • The new theory stems from decades of anecdotal observations that some autistic children seem to improve when they have a fever, only to regress when the fever ebbs.
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  • This study documented that autistic children experience behavior changes during fever.
  • Einstein researchers contend that scientific evidence directly points to the locus coeruleus–noradrenergic (LC-NA) system as being involved in autism. "The LC-NA system is the only brain system involved both in producing fever and controlling behavior," says co-author Dominick P. Purpura, M.D., dean emeritus and distinguished professor of neuroscience at Einstein.
  • The locus coeruleus has widespread connections to brain regions that process sensory information. It secretes most of the brain's noradrenaline, a neurotransmitter that plays a key role in arousal mechanisms, such as the "fight or flight" response. It is also involved in a variety of complex behaviors, such as attentional focusing (the ability to concentrate attention on environmental cues relevant to the task in hand, or to switch attention from one task to another). Poor attentional focusing is a defining characteristic of autism.
  • "What is unique about the locus coeruleus is that it activates almost all higher-order brain centers that are involved in complex cognitive tasks," says Dr. Mehler.
  • autism, the LC-NA system is dysregulated by the interplay of environment, genetic, and epigenetic factors
  • They believe that stress plays a central role in dysregulation of the LC-NA system, especially in the latter stages of prenatal development when the fetal brain is particularly vulnerable.
  • a higher incidence of autism among children whose mothers had been exposed to hurricanes and tropical storms during pregnancy.
  • autistic children, fever stimulates the LC-NA system, temporarily restoring its normal regulatory function. "This could not happen if autism was caused by a lesion or some structural abnormality of the brain," says Dr. Purpura.
  • future of autism treatment probably lies in drugs that selectively target certain types of noradrenergic brain receptors or, more likely, in epigenetic therapies targeting genes of the LC-NA system.
  • If the locus coeruleus is impaired in autism, it is probably because tens or hundreds, maybe even thousands, of genes are dysregulated in subtle and complex ways," says Dr. Mehler. "The only way you can reverse this process is with epigenetic therapies, which, we are beginning to learn, have the ability to coordinate very large integrated gene networks."
  • "You can't take a complex neuropsychiatric disease that has escaped our understanding for 50 years and in one fell swoop have a therapy that is going to reverse it — that's folly. On the other hand, we now have clues to the neurobiology, the genetics, and the epigenetics of autism. To move forward, we need to invest more money in basic science to look at the genome and the epigenome in a more focused way."
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    the brains of people with autism are structurally normal but dysregulated, meaning symptoms of the disorder might be reversible.
Tero Toivanen

Autism and early oxygen deprivation 2 | On the Brain by Dr. Mike Merzenich,Ph.D. - 0 views

  • Fraternal twins typically have different placentas, whereas identical twins share a placenta but have different cords. The blood supply, and pre-clamping susceptibility to anoxia, would surely be different.
  • As for the idea that one could statistically detect whether cord clamping is the problem, we can! Amish people do not clamp the cord until placental delivery, and they have no autism rate. The same is true in Somalia, but Somalian immigrants to westernized medical countries have high rates. Try to systematically find out autism rates and immediate cord clamping rates, on a country by country, or region by region basis. It is a task someone should get on immediately, but it will take a lot of effort.
  • An interesting discussion of the “Amish anomaly” re autism incidence has been provided by Dan Olmsted, who went to Amish Country to find the 150 or so individuals there who could be expected to be severely autistic. They aren’t there. He seems pre-disposed to believe that the difference lies with their non-vaccination. Many studies now show that this is unlikely. As David Blake points out, there is another difference in this population: In Amish birthing, by tradition, the cord is not clamped prior to placenta delivery.
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  • The picture with autism in Somali children is a little murkier. It turns out that the incidence of autism is very high in children of Somali origin who were born in the US (several times higher than normal), while it appears to be very low in Somali children born in their native country. Again, vaccination has been identified as the likely cause by Somali parents and by many observers — but again, clamping follows placental delivery in Somalia, while the cord has been clamped without delay as a general practice in Minnesota, where a high incidence of autism in these children of Somali immigrants was first discovered.
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    Comment about the hypothesis that early umbilical cord clamping might contribute to the risk of origin of autism.
Tero Toivanen

NIMH · Our brains are made of the same stuff, despite DNA differences - 1 views

  • “Having at our fingertips detailed information about when and where specific gene products are expressed in the brain brings new hope for understanding how this process can go awry in schizophrenia, autism and other brain disorders,” said NIMH Director Thomas R. Insel, M.D.
  • Among key findings in the prefrontal cortex:Individual genetic variations are profoundly linked to expression patterns. The most similarity across individuals is detected early in development and again as we approach the end of life.Different types of related genes are expressed during prenatal development, infancy, and childhood, so that each of these stages shows a relatively distinct transcriptional identity. Three-fourths of genes reverse their direction of expression after birth, with most switching from on to off.Expression of genes involved in cell division declines prenatally and in infancy, while expression of genes important for making synapses, or connections between brain cells, increases. In contrast, genes required for neuronal projections decline after birth – likely as unused connections are pruned.By the time we reach our 50s, overall gene expression begins to increase, mirroring the sharp reversal of fetal expression changes that occur in infancy.Genetic variation in the genome as a whole showed no effect on variation in the transcriptome as a whole, despite how genetically distant individuals might be. Hence, human cortexes have a consistent molecular architecture, despite our diversity.
  • Among key findings:Over 90 percent of the genes expressed in the brain are differentially regulated across brain regions and/or over developmental time periods. There are also widespread differences across region and time periods in the combination of a gene’s exons that are expressed.Timing and location are far more influential in regulating gene expression than gender, ethnicity or individual variation.Among 29 modules of co-expressed genes identified, each had distinct expression patterns and represented different biological processes. Genetic variation in some of the most well-connected genes in these modules, called hub genes, has previously been linked to mental disorders, including schizophrenia and depression.Telltale similarities in expression profiles with genes previously implicated in schizophrenia and autism are providing leads to discovery of other genes potentially involved in those disorders.Sex differences in the risk for certain mental disorders may be traceable to transcriptional mechanisms. More than three-fourths of 159 genes expressed differentially between the sexes were male-biased, most prenatally. Some genes found to have such sex-biased expression had previously been associated with disorders that affect males more than females, such as schizophrenia, Williams syndrome, and autism.
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  • Our brains are all made of the same stuff. Despite individual and ethnic genetic diversity, our prefrontal cortex shows a consistent molecular architecture.
  • Males show more sex-biased gene expression. More genes differentially expressed (DEX) between the sexes were found in males than females, especially prenatally. Some genes found to have such sex-biased expression had previously been associated with disorders that affect males more than females, such as schizophrenia, Williams syndrome, and autism.
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    Our brains are all made of the same stuff. Despite individual and ethnic genetic diversity, our prefrontal cortex shows a consistent molecular architecture. 
Tero Toivanen

Developmental abnormalities in the mirror neuron system may - 1 views

  • Developmental abnormalities in the mirror neuron system may contribute to social deficits in autism.
  • Now, a new study published in Biological Psychiatry reports that the mirror system in individuals with autism is not actually broken, but simply delayed.
  • While most of us have their strongest mirror activity while they are young, autistic individuals seem to have a weak mirror system in their youth, but their mirror activity increases with age, is normal by about age 30 and unusually high thereafter.
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  • This increase in function of mirror neuron systems may be related to increased capacity for social function or responsiveness to rehabilitative treatments among individuals with autism.
  • One of the next steps in this line of research will be for researchers to examine how individuals with autism accomplish this improvement over time, and how therapeutic interventions targeting the same mechanism can help to support this important process.
Tero Toivanen

Researchers define uniform method to interpret autism spectrum disorders - 2 views

  • This approach makes it easier to understand both commonalities and differences between ASD and other conditions, such as Attention Deficit Hyperactivity Disorder (ADHD). This approach will make it possible to test predictions about the location of these brain networks, how they function differently in people with ASD and how to use this knowledge to design interventions and compensatory strategies.
  • A recent study of a U.S. metropolitan area estimates that 3.4 of every 1,000 children between 3 and 10 years-old have Autism.
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    Dr. Dorit Ben Shalom recommends a uniform approach to evaluating and confronting the four common problems associated with ASD.
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