Molecular Explanation for Autism Reportedly Within Reach

A new  study appears to support the theory that a lack of chemical regulation between synapses is behind at least some cases of autism disorders. The new results are stated to be very preliminary and are discussed  at Molecular Explanation for Autism Within Reach :


"Autism is a disorder that affects numerous children around the world, but now experts appear to be closing in on the molecular agents that appear to underlie at least a portion of all autism cases.


Investigations have thus far been conducted on lab animals, cadavers, and even in a small clinical trials, and the results are encouraging.


The team behind the researches however draws attention to the fact that the work is still in its earliest days, and that even the results are preliminary.


But experts express their hope that one day they will be able to identify these troublesome molecules, and develop new cures based on them.


The main idea about autism that is getting support from the new investigations is that the condition appears due to a lack of chemical regulations in synapses.


These are the small spaces between neurons or nerve cells, through which electrical signals are being transmitted from one cell to the next via chemicals known as neurotransmitters.


The latest clinical trial to support this idea was conducted on about 25 children, all of which were aged 6 to 17. Cambridge, Massachusetts-based Seaside Therapeutics conducted the investigation ...."

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Autism and Intellectual Disability: One Synaptic Disorder Tied Together by APC Protein Dysfunction?

Intellectual Disability, or Mental Retardation, or Cognitive Deficit, pick your label, pick  your euphemism, pick your stigma, is officially described as a "co-morbid" condition associated with autism spectrum disorders. There are many in the "autism community", persons who have an autism spectrum disorder diagnosis, or  parents who have a child with an autism disorder,  who do not like any suggestion that autism disorders and intellectual disabilities are more than just co-morbid conditions, that they might be part and parcel of one disorder.  The stigma associated with intellectual disability is real and many in the high functioning autism and Aspergers community, including parents, want no part of it.

The fact that the "vast majority", 75-80% of persons with Autistic Disorder  and  41-44% of all persons with any type of autism spectrum disorder, (a number diluted by the inclusion of Aspergers on the autism spectrum which by diagnostic definition excludes a cognitive deficit or intellectual disability) have intellectual disabilities is dismissed as a co-morbidity .... as autism's biggest coincidence.   The "coincidence"  denial of the obvious connection between autism and intellectual disability  will be harder to maintain though in the face of a study from Tufts University, news release follows, in which the study authors found that a dysfunction of a specific protein, APC (adenomatous polyposis coli) which plays a key role in synapse formation required for learning and memory provides a clue to the causes of autism and mental retardation:

Researchers Connect APC Protein to Autism and Mental Retardation 

BOSTON (August 23, 2010) — A clue to the causes of autism and mental retardation lies in the synapse, the tiny intercellular junction that rapidly transfers information from one neuron to the next. According to neuroscientists at Tufts University School of Medicine, with students from the Sackler School of Graduate Biomedical Sciences at Tufts, a protein called APC (adenomatous polyposis coli) plays a key role in synapse maturation, and APC dysfunction prevents the synapse function required for typical learning and memory. The findings are published in the August 18 issue of The Journal of Neuroscience.

“Both sides of the synapse are finely tuned for efficient transmission; an imbalance on either side can negatively impact function, resulting in cognitive deficits. Our study reveals that APC forms a key protein complex in the postsynaptic neuron that also provides signals to direct synapse maturation in the presynaptic neuron, ensuring that the two sides of the synapse mature in concert to provide optimal function,” said senior author Michele H. Jacob, PhD, professor in the department of neuroscience at Tufts University School of Medicine. Jacob is also a member of the cell, molecular and developmental biology; cellular and molecular physiology; and neuroscience program faculties at the Sackler School of Graduate Biomedical Sciences at Tufts.

In the in vivo study, the team blocked APC function and found that synaptic levels of the cell adhesion proteins neuroligin and neurexin dropped considerably. Without normal levels of these proteins, synapses were less mature both structurally and functionally. Mutations in the genes for neuroligin and neurexin are associated with autism in humans, but until now, little was known about the mechanisms responsible for localizing these proteins at the synapse. “Our laboratory study is the first to show that APC is needed to recruit neuroligin and neurexin to the synapse. This finding provides new insights into the mechanisms required for proper synapse function as well as molecular changes at the synapse that likely contribute to autistic behaviors and learning deficits in people with APC loss of function gene mutations,” said Jacob.

“Our study also sheds light on a poorly-understood but essential process, the cross-talk that occurs between presynaptic and postsynaptic neurons. When we perturbed APC function on the postsynaptic side, we saw changes on both sides of the synapse, indicating that APC organizes a protein complex that communicates against the normal flow of traffic,” said first author Madelaine Rosenberg, PhD, an affiliate of the department of neuroscience at TUSM.

The research team’s next step is to examine the behavioral and cognitive changes that occur when APC is deleted in neurons of the mammalian brain. They have developed a new mouse model that will allow them to investigate how the loss of APC function leads to synaptic changes and impaired learning and memory.

Additional authors are Fang Yang, PhD, a research associate in the department of medicine at TUSM; Jesse Mohn, a PhD candidate in the cell, molecular, and developmental biology program at Sackler and member of Jacob’s lab; and Elizabeth Storer, a PhD candidate in the neuroscience program at Sackler and member of Jacob’s lab.

This study was funded by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health, and the Tufts Center for Neuroscience Research. The Tufts Center for Neuroscience Research, itself, is supported by NINDS and by Tufts University School of Medicine and Tufts Medical Center.

Rosenberg MM, Yang F, Mohn JL, Storer EK, Jacob MH. The Journal of Neuroscience. 2010. (August 18); 30(33): 11073-11085. “The Postsynaptic Adenomatous Polyposis Coli (APC) Multiprotein Complex Is Required for Localizing Neuroligin and Neurexin to Neuronal Nicotinic Synapses in Vivo.” Published online August 18, 2010, doi: 10.1523/JNEUROSCI.0983-10.2010

About Tufts University School of Medicine and the SacklerSchool of Graduate Biomedical Sciences

TuftsUniversitySchool of Medicine and the Sackler School of Graduate Biomedical Sciences at TuftsUniversity are international leaders in innovative medical education and advanced research. The School of Medicine and the SacklerSchool are renowned for excellence in education in general medicine, biomedical sciences, special combined degree programs in business, health management, public health, bioengineering and international relations, as well as basic and clinical research at the cellular and molecular level. Ranked among the top in the nation, the School of Medicine is affiliated with six major teaching hospitals and more than 30 health care facilities. TuftsUniversitySchool of Medicine and the SacklerSchool undertake research that is consistently rated among the highest in the nation for its effect on the advancement of medical science.

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If you are a member of the media interested in learning more about this topic, or speaking with a faculty member at the Tufts University School of Medicine, the Sackler School of Graduate Biomedical Sciences, or another Tufts health sciences researcher, please contact Siobhan Gallagher at 617-636-6586.

Contact:

Siobhan Gallagher

617-636-6586

siobhan.gallagher@tufts.edu

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Dr. Thomas Armstrong Romanticizes Autism Disorders and Autism's Gadfly Holds Him Accountable

Yesterday I commented in Synaptic Disorder Instead Of Autism Spectrum Disorder? on the romanticization of autism disorders by those who subscribe to the Neurodiversity ideology.  At Autism's Gadfly Jonathan Mitchell has dissected a very blatant example of  romanticization and misrepresentation of autism disorders. 

In Thomas Armstrong's book on neurodiversity Jonathan describes as offensive the title of Dr. Armstrong's new book "Neurodiversity discovering the extraordinary gifts of autism ADHD, Dyslexia and other brain differences. "  I agree with Jonathan's description of the book title as offensive. I  refer you to Jonathan's commentary for the details but, as the father of a boy who is severely affected by Autistic Disorder, whose life will be one of living dependent on the care of others,  I am sick and tired of careers being made, and books being sold, by people promoting flimsy, unrealistic, misrepresentations of autism based on the  successes of a few high functioning persons with autism or Aspergers.  

As I said yesteday, maybe it is time to drop the "autism" label altogether and look at Autism Disorder as Synaptic Disorder.  "Synaptic" doesn't sound like it would be as  easy to market, and misrepresent to a gullible mainstream media, as "autism".

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Synaptic Disorder Instead Of Autism Spectrum Disorder?

The word "Autism" has become romanticized, occasionally glorified, in public discussions of the neurological disorder. It is literally being stripped of its meaning as a diagnostic label of a mental disorder and is being turned into a different way of thinking, a way of life, a culture. Maybe it is time to start thinking about dropping the use of the term autism in the DSM, abandon the Autism Spectrum Disorder concept and replace it with a more informative, less romanticized, less politicized  name ... Synaptic Disorder.

At its most extreme the glorification of autism spectrum disorders has seen historical talents and geniuses from Mozart to Einstein "diagnosed" long after their deaths as  having been "autistics". One of the silliest of such fantasies is the speculation that Jesus Christ was autistic. At the other end of the stigma spectrum are those aided by the American Psychiatric Association, and its dilution of the concept of autism disorders in the DSM-IV,  who want the world to believe that autism and intellectual disability are unrelated conditions that are "coincidentally" present in 75-80% of those with Autistic Disorder and between 40 and 50% of all persons with autism spectrum disorders. 

Maybe it is time to consider abandoning use of the term "autism" altogether and replace it with a new, more informative, and less politicized term .... synaptic disorder.  In his December 2009  Simons Initiative on Autism and the Brain Lecture at MIT, "Autism, What Do We Know? What Do We Need?",  Dr. Thomas Insel, Director of the National Institute of Mental Health (NIMH) acknowledged that autism is not fully explained by genetics. It is also necessary to consider environmental factors ( a point made 10 years earlier by Teresa Binstock and emphasized by many autism authorities including Dr. Irva Hertz-Picciotto).  Dr. Insel also discussed the matter of how we describe autism disorders and whether we are talking about these disorders in ways that are helpful to understanding them biologically as summarized on the MIT World review of his lecture:

"The formal definition of autism includes three main components: deficits in social behavior, abnormal language, and repetitive or restricted (motor) behaviors (hand flapping, for instance). But it can also include a host of other associated features like seizures, mental retardation, GI disorders, dysmorphic appearance, and regression.

Insel compares talking about autism as a single disorder to talking about epilepsy or fever or chest pain as a single disorder. Discussions must include understanding details at many levels—genetic, environmental, cellular, behavioral, systems. While researchers may now increasingly refer to autisms (plural) or think of the disorder along a spectrum, these categories may cause more problems in getting to the underlying biology of the disorder. Current research suggests that autism is a developmental brain disorder, specifically a disorder of synapses." (Bold emphasis added-HLD)

Given Dr. Insel's view, as Director of the NIHM, speaking at MIT, that autism is a synaptic  disorder  would  it not be prudent for the DSM-5 team to hold off on  another transformation of the pervasive developmental disorders, already spoken of as autism spectrum disorders, until the research confirms (or refutes) the view that autism is a disorder of synapses?  Dr. Insel has indicated that describing autism as a disorder of synapses, synaptic disorder, may be more helpful in getting to the underlying biology of the disorder.

Synaptic Disorder instead of Autism Spectrum Disorder? Surely it should at least be considered by the American Psychiatric Association  as it once again revises the DSM. 

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