Recently we had the opportunity to publish a blog at the Autism Science Foundation (ASF) web site (see http://bit.ly/1zJHtey). The same summarizes the main intent of one of our latest articles published in Frontiers in Cell Biology. The article is freely available online (http://bit.ly/1CZ2xya). The article suggests that there is a cascade of interdependent developmental processes that are affected in autism. For some researchers, to say that autism is simply a synaptic disorder is therefore naïve and ultimately offers only a myopic view of the available literature. Due to their formatting guidelines the original blog that we wrote was cut in half by the ASF. I reproduce the same in its entirety in the next few paragraphs.
By Emily L. Casanova, Ph.D. & Manuel F. Casanova, M.D.
Science, like any area of study, goes through trends. At any given time, particular ideas may be more or less popular, not necessarily because of their merit alone but because they support points of view that are en vogue. In 2003, Dr. Thomas Bourgeron and his team published evidence that identified mutations in two synapse-related genes in a pair of autistic siblings, the first in a long line of evidence that has supported the notion that synapses are dysfunctional in autism. That same year, partly based on Bourgeron’s work, Dr. Huda Zoghbi took up the gauntlet by proposing that autism was a disorder of the synapse. Since that time, the study of synaptic development has received much attention in the field of autism research. However, if one studies the brain in autism, either through postmortem work or brain imaging, one finds that most cases of the condition display brain abnormalities characteristic of early developmental disturbances. Examples of these disturbances include the displacement of neurons, changes to the overall complexity in the shape of the brain, and cerebral malformations. These findings, along with the known neuropathology of many syndromic autistic disorders such as Tuberous Sclerosis, help sustain the view that autism is generated during early brain development.
In humans, the production of new neurons continues up into the early part of the third trimester. Synapses, on the other hand, are formed in successive waves later in the prenatal period and after birth, providing portals through which neurons may communicate with one another. Current evidence stresses the importance of early brain development in autism risk, however it also raises an important question: How can both early and later brain developments be targeted in autism?
Our laboratory has focused on the idea that many stages of brain development are affected in most cases of autism. In our most recent publication in Frontiers in Cellular Neuroscience, we report that most of the high-risk gene mutations associated with autism impair not only later synapse development but also earlier stages of neuron production and maturation. This tells us that autism is more than just dysfunctional synapses, it’s dysfunctional neurons and neuronal networks. This understanding is vital, not only so we can decipher how this heterogeneous condition develops, but also to be able to predict the different ways in which it might be treated or even prevented. In order to design successful treatments, we must know precisely what we’re dealing with.
Our recent work also helps bridge the gap that has developed between subfields of autism research, resolving differences between those scientists who study prenatal versus postnatal development. In essence, these groups have been studying different sides of the same coin. We can see this in the way that nature has tinkered with brain development: instead of developing new mechanisms for postnatal synaptic development, it has borrowed many of them from preceding evolutionary processes like cell division and migration that characterize prenatal brain development.
Determining the ways in which the brain is affected in autism may also help us understand how regressive autism arises, and how these cases may be similar and/or different from typical forms of the condition. For instance, the childhood epilepsy known as Dravet Syndrome (DS) presents with normal or relatively normal cognitive development throughout the first year of life. Yet between ages 1-2 years these children develop seizures often in response to fever or illness. Following seizure onset, approximately 25% of these children also develop symptoms of autism, making DS a well-recognized form of syndromic autism. However, individuals with DS also exhibit brain malformations similar to those seen in typical and syndromic autism. Because these malformations occur very early in brain development, this indicates that DS, and perhaps other forms of regressive autism, have prenatal roots even though symptoms aren’t obvious until 1-2 years of age.
This work stresses the need for a paradigm shift in autism research and a broader understanding of how the brain develops. While it may be simpler to study a single structure or developmental stage, a tunnel-vision approach may not provide us with an accurate understanding of what has occurred to produce the condition we’re investigating. We hope that a broader developmental point of view is a step in the right direction, helping to bring together different branches of research so that their results complement each other rather than confuse the field. Autism, after all, is a puzzle. We need to be looking at all the pieces together.
Dear Dr. Casanova,
I just read your article with great interest. That means my “theory” regarding the incapability in autism to get the world in sequences (of words & images) is essentially correct.
That is why we have no faculty for recalling memories in an orderly (sequential) fashion. Japanese author Naoki Higashida (who is severe autistic) noted in The Reason I Jump, “Memories are not stored in a clear order. Our memory isn’t like a number-scale from which you pick out the recollection you are after: it’s more like a jigsaw puzzle, where if even just one piece is misinserted, the entire puzzle becomes impossible to complete. What’s more, a single piece that doesn’t belong there can mess up all the surrounding memories as well.”
That is why we cannot assimilate the ready-made knowledge and skill that others present to ourselves.
That is why we are unable to build up “automatic programmers” through practice and habit.
That is why we have a lack of concentration to a high level.
That is why we have characteristic difficulties of automatization. The automatization of learning, that is, the setting up of routine thought processes, proceeds only with the utmost difficulty.
That is why we often confuse letters, have spelling deficiencies and the greatest difficulty in blending letters together. Orthography too is difficult to automatize.
That is why we have difficulty in retrieving our knowledge (what we have learned) which is revealed often by chance.
That is why visual aids, like pictures, can help us a lot.
This is my question: Could it be possible that this disruption in the otherwise well-coordinated network of cells and lack of neuronal maturation which is disturbed in autism is a consequence of a development that occurred late in the process of evolution?
I think so. I think that humankind throughout the ages has always intuitively known it and somehow helped the process of network synchronization through the creation of languages first and then myths and stories in order to explain ourselves. Did not Evolution have to split the brain’s functions in two to accommodate speech? As Leonard Shlain wrote in Alphabet versus Goddess:
“For the first two million years of evolution, both the hominid’s body and brain slowly enlarged. And then over the next one million years, a remarkable change occurred: while its stature increased only minimally, its brain acquired one extra pound of neural tissue, primarily in the neocortex. At the same time, the brain’s functions split in two—a revolutionary development made necessary because evolution had to rewire one lobe to accommodate speech.”
My hypothesis is justified when I learned that, not surprisingly, the autistic brain shows «system failure» in almost every function of the left-brain – the functions that make us human. I know that the left-brain finishes its development behind that of the right, which, I suspect, could leave the left susceptible to many factors that can disrupt brain function.
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You ask all of the hard questions. I do not have an answer. Many of the evolutionary genes that created the big brains and allowed for socialization were mutated only 20,000 to 60,000 years ago. If you are interested some of these genes include ASPM and the FOXP2. Continue being creative.
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