I suspect that most of the knowledge necessary to understand autism already exists. I believe that the causal mechanism of autism has not been identified because modern science is poorly equipped to piece together the components of this extremely complicated puzzle whose solution requires the integration of many diverse scientific disciplines such as sociology, psychology, endocrinology, neurology, genetics, and immunology. Integration is not the hallmark of the scientific method as carried out today. Science is all about specificity. Researchers break down problems into the smallest component parts so that in establishing causation, they can strip away variables and achieve statistical significance. This is a very effective way of understanding many problems. However, I don't think it will solve the mystery of autism any time soon.
I theorize that it is possible using logic combined with a basic understanding of numerous scientific disciplines to integrate the puzzle pieces into a valid and useful logical construct, what some scientists will dismissively describe as a ‘grand unified theory’, a non-scientific venture. Ultimately, this consists of building what lawyers would call a circumstantial case for the cause of autsm, which is all you can do when causation is so complex to elude scientific proof. This is adequate in a court of law to allow conviction; the law accepts a lack of complete and direct proof and the possibility of mistake because pragmatically it is the only way to achieve justice in certain circumstances. While this theory may have various scientific flaws, this does not mean it is not a relatively accurate theory of how autism works that could guide parents, caregivers, doctors and others who have to deal with the reality of autism in their lives.
There are two particularly important, but very different, questions in deciphering the causal chain of autism in an effort to establish such a unified theory. First, what has caused autism to be seemingly present at relatively low levels stretching back thousands of years? Second, what has caused the sizable increase in autism incidence in the last 50 years?
What Causes the Ambient Level of Autism in History?
Vastly simplified, my theory is that autism is not ultimately a disorder unto itself, but instead a series of behaviors engaged in and deficits experienced by persons who are neurologically hypersensitive to the sensory and psychosocial stressors in their world. This means that the nervous systems, including and especially the brains, of those with autims are excessively excitatory, with too much electrical activity coursing through their electrical circuits at all hours of the day. Hypersensitivity results from this excess of neural activity, as information about the surrounding world is processed up to the brain with too little filtering and too much amplitude.
This neurological hypersensitivity can occur in three primary ways, the first two of which are well accepted as causes of autism, or at least autistic-like behaviors, though the mechanism of causation is not understood. First, the person may have a severe genetic abnormality, such as Rett Syndrome or Fragile X syndrome, that, among other things, results in a nervous system that is overly sensitized to the outside world. Second, the person may have been exposed (most often prenatally) to a substance such as excessive alcohol, methyl mercury, or valproic acid, which affected the development of their brain in a way that resulted in an overly excitatory nervous system. These first two causal mechanisms are estimated to account for no more than 10-15% of all autism diagnoses.
The Third Group - Idiopathic Autistics
It is the third category that is wrapped in tremendous mystery – all the other people who get autism without a simple, identifiable, single vector causal chain underlying their condition - the idiopathic autistics.
I hypothesize that the unifying factor behind the vast majority of these cases is that these individuals are predisposed to autism because evolution dictated that their genetic line be more sensitive on average to external stressors than most other humans. It altered the balance in these individuals’ nervous systems towards a higher level of electrical excitation than normal, providing them a more intense experience of the sensory world around them and a unique way of processing information that offered benefits to their tribe, though a much greater risk than normal of developing autism because their excitation levels have been pushed to the ragged edge of where problems start to show up.
This genetic variation occurred because of the survival advantages to the group that having a limited number of individuals wired this way conveyed – there are benefits of having individuals who are extremely sensitive to physical threats to the group, uniquely able to spot patterns that might indicate the presence of a threat, and able to think in orderly and systematic ways. Simon Baron-Cohen calls this the ‘extreme male brain’, a brain which provides benefits to the tribe, but offers a potentially difficult existence to the individual with it.
This inherent neural hypersensitivity may result in autistic symptoms in a person if 1) their excessively sensitive nervous system was sufficiently excitable in the face of a historically normal human environment (like living in a stable family in a small village in a forest with limited access to modern technology) to result in substantial dysfunction, or 2) their more-sensitive-than-average nervous system (which is less excitatory than that of a person in class 1) above), which would not be adequately sensitive in a historically normal human environment to result in significant dysfunction, mixed with a sufficiently toxic environment during their prenatal and early postnatal life (like a low-nurture early childhood or very poor maternal health during pregnancy) in a way that disrupted numerous of the normal homeostatic balances in their nervous, endocrine and other systems, resulting in autistic dysfunction.
Neural Balance - The Role of Glutamate and GABA
The level of neural sensitivity in any individual results primarily from a balance in the brain between two neurotransmitters, glutamate and GABA, which balance is determined by a complex interplay of genetics and environment. Glutamate is the primary excitatory neurotransmitter in the human brain, bearing responsibility for charging the human nervous system and making it function electrically. GABA is the primary inhibitory neurotransmitter in the human brain, channeling and restraining the nervous system in a way that allows it to function normally. Autistic dysfunction can result from too much glutamate, too little GABA, or both. Much of the diversity in the autism spectrum (i.e. which individuals with autism develop seizures and where they are located) is driven by how this imbalance is caused: whether the imbalance is local (i.e. constrained to a specific neural circuit, like the cerebello-thalamo-cortical circuit) or global (i.e. resulting from insufficient inhibition at the brainstem where much sensory information is modulated) or whether the imbalance results from too much glutamate (i.e. as occurs in ethyl mercury poisoning) or too little GABA (i.e. which may happen when the Purkinje cells of the cerebellum are degraded – which is the most consistent anatomical finding in autism).
The Involvement of the Human Stress Response
This neurological hypersensitivity triggers the involvement of the other primarily involved biological system: the human stress response as mediated by the nervous and endocrine systems. The exaggerated sensitivity in autism results in a stress response that is triggered much more easily than in a neurotypical person. This is because the heightened neural sensitivity results in the brain perceiving many more components of the individual’s sensory world as threats (such as emotional tone in normal human interaction), activating the stress response (which helps protects against external threats) much more frequently. The autistic individual is almost constantly under at least low grade stress response activation, as indicated by chronically elevated/abnormal cortisol levels, abnormally high levels of adrenaline and noradrenaline, and the elevated presence of many substances that are secreted or produced in greater quantities in response to stress, such as vasoactive intestinal peptide, brain derived neurotrophic factor, and substance P.
The abnormality in cortisol secretion is particularly important in this process. Cortisol causes changes in the brain, and is likely responsible for the decreased hippocampal volume and increased amygdala size seen frequently in autism, both of which changes tend to allow fear responses to become uninhibited, which contributes to the anxiety chronically present in autistic children. Cortisol increases neural hyperexcitability by sensitizing neurons in the brain to the effects of glutamate as well as impairing the ability of GABA to inhibit glutamate, both of which create positive feedback loops that sustain the autistic downward spiral. And, cortisol works with the other stress hormones to stoke the inflammatory processes of the immune system in a way that results in chronic inflammation.
Autistic individuals have clear indications of chronically activated inflammatory systems. This shows up in altered immune system function, elevated levels of cytokines and chemokines (such as interleukin-6 and tumor necrosis factor alpha) which signal inflammatory activation, particularly in the brain, and altered numbers and function of brain cells called glial cells that support neuronal function often by adjusting and controlling the levels of neurotransmitters like glutamate and GABA. Moreover, this chronic inflammatory activation causes sensitization of the sensory pathways of the peripheral nervous system, loading even greater levels of sensory information on a nervous system already overwhelmed due to the excess excitation in the brain.
Anything and everything in the autistic individual’s environment can act as a threat to set off the stress response cascade, from a changed furniture arrangement, to background noise, to eye contact, to fluorescent lights, to the stress of getting up in the morning. The autistic’s world is one of hypervigilance, constantly scanning the world for threats, for patterns that help the autistic to control and predict the threatening world, and for the underlying workings of the systems that control the world, like mathematics and science.
In response to this hostile world, the autistic individual attempts to cope in a way that minimizes their pain and challenge in the world. The behaviors that typify autism are largely attempts to cope with a world that is toxic to their nervous system (i.e. control seeking through habits and rituals, distracting through rocking or flapping, or stress relieving through hyperactivity) or the results of their failure to cope (i.e. a melt down). The normal behaviors autistics fail to engage in are the result of efforts to avoid exposure to too much information (i.e. they fail to look at faces or eyes because the emotional content of that action overwhelms them). The deficits that they often exhibit (i.e. lack of emotional reciprocity) result from adjustments their brain and nervous system have made in order to function as best they can in this overwhelming world. Their difficulties with language and communication may result from many factors, such as a brain that is rushing too fast for them to keep up with due to excess excitation, an unwillingness to elicit a response that may be loaded with offensive emotional content, an overstimulated auditory system that distorts their perception of language, or a simple lack of interest in interacting with a world that continually causes them pain. And, the sensitivities that they exhibit (i.e. inability to tolerate light touch or loud noise) result from a nervous system that fails to properly attenuate and manage the sensory information flowing to their brain through their peripheral nervous system and brainstem. Their subjective experience of the world, to quote a book title on sensory processing disorders, is too loud, too bright, too fast, too tight.
What is Causing the Modern Increasing Incidence of Autism?
Human disease and dysfunction result from a complex interaction of genetics and environment. In the absence of a significantly changing environment, human diseases such as cancer typically reach relatively stable levels of incidence - equilibrium.
When the incidence of a disease starts to change quickly and dramatically (i.e. the rate of lung cancer in humans in the 20th century), logic demands that the core cause of this increase is environmental (an increase in exposure to cigarette smoke). Genetics simply cannot change quickly enough in humans in order to play a significant role in causing drastic shifts in disease incidence.
There is a heated debate on how much of the drastically increasing diagnosis of autism results from an actual increase in incidence and prevalence. Many, particularly those who believe vaccines cause autism, point to an autism epidemic. Others, including many scientists who are reacting to the media frenzy over the perception of an epidemic of autism, argue that there is no compelling evidence that autism rates have increased at all; studies that have been published argue that the increase in autism diagnosis can be explained by various factors including the growing popularity of the diagnosis, diagnostic substituion, a widening definition of autism and other factors. I personally believe, and will shortly publish on this site my research on this topic, that autism incidence and prevalence rates have in fact gone up substantially (maybe up to 5 times what it used to be), particularly on the high functioning side of the spectrum. However, the claims of a modern epidemic for a disease that didn't exist at all 30 years ago are specious for various reasons.
Even a doubling of autism incidence and prevalence would be a dramatic increase in the impact autism is having on our world. Imagine a doubling of cancer cases in a 20 year period of time and the panic that would cause. That type of increase of any disease cannot be accounted for by a change in human genetics because of natural selection or other types of mutation. Genes just don't change that quickly. Changes that occur that quickly have environmental causes - such as tobacco causing lung cancer or modern dietary ane exercise patterns causing type 2 diabetes. Changes in our environment logically must dominate the causal pathways behind the increase we are seeing in autism.
This raises the most important question, which few scientists are interested in today, probably because the causal chain is highly complicated and hard to study conventionally: which changes in our environment are causing the escalating rates of autism in the third category of people described above?
What Environmental Changes are Most Important
I theorize that the changes involved are everywhere. They have become part of a modern culture that we have created. We have changed our environment so drastically that our current environment is simply biologically unrecognizable from the places humans evolved – the places where the homeostatic balances that underlie human biology were established. Everything is different, from the foods we eat, to the way we live, to the way we get around, to the manner in which we spend our free time. 10,000 years ago, there were no cars, no vacuum cleaners, no pop tarts, no fluorescent lights and no television. 10,000 years ago, stress relieving movement was built into the fabric of our lives – not any more. 10,000 years ago, we lived every day in harmony with the rhythms and beauty of nature – few of us do so today. The habits and experiences of a tribe of hunter gatherers bear no resemblance to the lives of office workers or motor sports enthusiasts. And, this change has not gone biologically unnoticed.
As our environment has changed, in a timeframe too quickly for evolutionary adaptation, our biology has changed, and for the most part these changes have been extremely negative. Heart disease, many types of cancer, obesity, autoimmune conditions, gastrointestinal dysfunction and many other conditions have resulted from the way we now live. These conditions are often called diseases of western civilization. Highly elevated autism rates is simply one more disastrous outgrowth of the world that we have created for ourselves. This changed way of living, this massively modified environment in which we live every moment of our lives, is the trigger that pushes the already sensitive nervous systems of this dramatically expanding third group of people into hypersensitivity to an increasingly neurologically toxic world, resulting in positive feedback loops that starts these people on a cascade to autistic dysfunction the moment they are conceived.
What are the most important elements of this westernized world related to autism causation? The answer is uncertain, and probably different for every individual. However, we can make some logical guesses that can be experimentally validated over time. The answer is likely similar to the causal mechanisms underlying the other diseases of westernized civilization. Take type 2 diabetes. The causal mechanism behind its prominence likely involves obesity (which is driven by an imbalanced human diet compounded by a sedentary lifestyle), a diet dominated by simple carbohydrates eaten in isolation from food that slows digestion, inadequate sleep (which reduces resilience to stress and negatively impacts glucose metabolism), and a chronically stressful existence which exacerbates all of the other causal vectors as well as having its own ravaging consequences mediated mainly by cortisol. Take cardiovascular disease. Its causal chain probably includes obesity (which leads to chronic inflammation and overloaded demand on the heart), a diet rich in saturated fats (which causes platelets and other cells to become sticky leading to clot and plaque formation), a diet deficient in omega 3 fatty acids (which allows the body’s cholesterol, which is normally mostly embedded in cell membranes, to escape into the blood stream), and a generally stressful environment (which causes elevations in blood pressure and other negative consequences).
These westernized diseases all have relatively similar causal chains, rooted in the dysfunctions of western civilization: bad eating habits, limited exercise and movement, poor sleeping patterns, a lack of daily relaxation and real enjoyment, degraded interpersonal engagement, and lots and lots of stress. And, the types of stress we are subjected to are much greater than the average person would understand. Riding in a car is a profoundly stressful experience: vibration of all types, too much noise, limited control over the surrounding vehicles, and no way to use movement to bleed off that stress - this is where road rage comes from. So is shopping at Walmart, with the constant din and awful fluorescent lighting. Watching TV is stressful as well. It may feel stimulating, with all that violence and emotional conflict, but stimulation is just one type of stress that is perceived as positive but still results in stress response activation. An increasingly large proportion of the activities we engage in, from playing video games, to racing motorcycles, to shopping at the mall involve stress response activation as a way of the body attempting to normalize a nervous system that is not being given a chance to recover. And, this stress, which is not compensated for by behaviors and activities that calm us, is driving us into nervous system imbalance, the cornerstone of autism.