Autism Disorder as Synaptic Disorder: Dysregulation of Neural Networks Causes Autism?

"In summary, Ehlers and colleagues (Lee et al., 2010) use infection of a tetanus toxin light chain to silence isolated synapses and uncaging of glutamate at single spines to reveal priming of individual synapses for LTP. The authors show that the underlying molecular mechanism involves an increase in NMDA receptor number and a switch in NMDA receptor phenotype from NR2A-containing to NR2B-containing receptors. Alterations in postsynaptic NMDA receptors are associated with an increase in postsynaptic Ca2+ and increase in the NMDA component of the EPSC. These findings are significant in that they show for the first time that metaplasticity, once thought to be a process involving a global change in the biophysical properties of entire neural networks, can occur within a single synapse. Understanding how changes in NMDA receptor number and subtype alter the threshold for potentiation is likely to cast light on the molecular mechanisms involved in plasticity and priming in general and increase our understanding of how neural networks participate in higher cognitive function, including learning and memory, and how their dysregulation causes neuropsychiatric disorders, including autism."

Synapse-Specific Metaplasticity: To Be Silenced is Not to be Silenced 2B

The emphasis in this article, and the Lee et al  study it  previews, is on plasticity changes in single synapses.  This humble father of a son with Autistic Disorder does not pretend to have the knowledge of the subject matter or the jargon to follow the logic of the discussion without a great deal of effort and research.  I do find it interesting to note how some of the concepts of which I have some degree of understanding  are almost casually mentioned as factual.  Autism is clearly identified as being caused by dysregulation of neural networks in a very unqualified manner.  It is also interesting how the neural networks are described as participating in higher cognitive functions ... making a clear association between dysregulated  cognitive functions and autism. 

It is  refreshing  to see autism discussed objectively as a synaptic disorder.involving cognitive challenges, not glorified or misrepresented. Hopefully our increasing understanding of the synaptic bases and functions involved in autism disorders will some day result in treatments to help autistic persons who want to overcome their disorders and the families who seek treatment for their children affected by autism disorders.

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. 

Autism and Nicotine Addiction - The Neurexin Connection

Science Daily reports on findings presented by Rene Anand, associate professor of pharmacology in Ohio State University’s College of Medicine and principal investigator of research presented today at the at the Society for Neuroscience meeting in Washington, D.C. The findings identified a relationship between two proteins in the brain that have links to both nicotine addiction and autism suggesting a possible drug therapy to alleviate some symptoms of autism.

The neurexin-1 gene produces a protein which lures another protein "a specific type of nicotinic acetylcholine receptor, to the synapses, where the receptor then has a role in helping neurons communicate signals among themselves and to the rest of the body." Persons with autism have previously been found to have a shortage of nicotinic receptors in their brains while people who are addicted to nicotine have too many.

There is some speculation that drugs known as cholinergic agents, used to counter nicotine addiction, could be adjusted for use in autistic children in an effort to increase the level of neurexin-1 beta protein in their brains. It is hoped that more neurexin would alleviate some of the symptoms of autism by encouraging the presence of more nicotinic acetylcholine receptors and number of other proteins important for the proper formation and maturation of synapses.

These cholinergic agents already exist so presumably they will be adjusted for autism as described and their effectiveness tested in the near future.

The Autism Knowledge Revolution continues.

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