Could Autism be seen as a Stress Adaptation?
Author: Lori Hogenkamp, B.A. Psychology
Edited: July 24, 2018
……ABSTRACT/INTRO in works….
On the cellular level, stress, or how the body-brain maintains homeostasis, is through complex physiological responses called allostasis (McEwen, 2017). These various stress coping strategies and trade-offs are quite individualistic, on both the social and cellular levels (Ebner and Singewald, 2016).
It would be a mistake to think of stress so simply as anxiousness. Because at its foundation, stress is the medium in which our genes communicate with our environment. The core communication of survival and evolution (Hammerlund et al., 2018 in ScienceDaily) .
A stress framework would be a working description of the patterns and compilation of hits and allostatic loads that impact adaptive programming. The combination possibilities are vast (Schaafsma et al., 2017) and act together in a synergistic fashion (Fatemi et al., 2012; Lombardo et al., 2017).
When it comes to stress and the relationship to autism, we find evidence riddled throughout the literature. Stress mechanisms are found in the biomarkers of autism (Goldani et al., 2014; Zaman et al., 2016; Wang, 2016; Howsmon et al., 2017), the collection of environmental impacts (Modabbernia et al., 2017), genetic signaling channels (Kim et al., 2016) and the neurotransmitter (Cetin et al., 2015) pathways. The diverse array of genetic and environmental factors involved in autism, the nurture that is running contrary to our nature, are likely causative within this complex relationship of stress balances (Francis and Kaufer in The Scientist, 2011;Traynor and Singleton, 2010).
What are Stress Mechanics?
What makes a stress stressful and subsequently adapting the system, is a variety of influences such as; Genes, Behavioral Genetics, Personality, Epigenetics, Previous Programming, Significant Deficiencies, Age, Timing, Gender and Context of Stress.
Genetics can represent both functions, such as personality and information processing and dysfunctions, such as single-gene diseases. The functions could represent unique stress sensitivities of personality types, while the genetic diseases have high levels of oxidative stress as a core feature mimicking the personality-stress phenotype.
Programming can cross generations, referred to as Transgenerational Epigenetics or Ancestral Programming. Programming from stress occurring at conception or in the womb is referred to as Prenatal Stress or Early Life Stress.
Deficiencies are an important factor to consider when stressors become stressful enough to create programming changes. Such deficiencies may come from the Microbiome, Fatty Acids, or artificial lighting.
There are quite a few Cellular Stressors implicated in autism, such as: Maternal Stress, Maternal and Paternal Health, Pesticides, Endocrine Disruptors, Mitochondrial disturbance, Viruses, Infections, Pharmaceuticals, Chemicals, Metals, Trauma, Pollutants and Social Stress. Early life stress programming can also create greater impacts to later life stress.
These Later Life stressors include: Hyper/hypo-sensitivity to lights, sounds and sensory inputs, growth stages, hormone changes, social expectations and social isolation. And lastly when we take a Systems Approach the same inputs can create variable and multi-layered Outcomes: Core symptoms of autism include atypical sensory, RRBIs, social and communication disturbances, along with interoception, alexithymia, digestive issues, unique immune activation, skin disorders, sensory atypicality, seizures, metabolism and circadian disturbances. Co-occurring and overlapping disorders include anxiety, depression, aggression, schizophrenia, bipolar and ADHD.
What are the Stress Variables?
Personality and Stress Resiliency
The definition of personality is similar to the many words for snow. Dozens of different definitions, layers and dimensions to this single word. Personality consists of character, traits, temperament and information processing types.
There are many factors of personality that are inherited; genetic, epigenetic, neurochemical and hormone factors. There are also environmental and social influences that can factor into the expression of an individual’s personality. Instead of looking at individual genes for the gene-environment influences, we could look at personality or information processing differences as a collection of genetic “hubs”. Since personality traits and information processes could reflect evolutionary patterns of vulnerability, plasticity and adaptability to stress.
Ultimately it will be quite complicated because it’s not like everyone is just one personality, trait, temperament or characteristic. Dr. Helen Fisher, biological anthropologist, discusses that each degree of these brain systems is expressed in different people. “We’re not all dopamine. We’re not all serotonin,” Dr. Fisher says. “We are a combination of all of them. But we express some more than others. And that’s what creates our basic personality.” So the ability to test this will be fuzzy, but if can we can see the patterns, collect enough evidence and build a model of stress mechanisms. Do we see enough stress and evidence of stress associated with autism to support this theory?
If stress is how the environment impacts and adapts, then personality, the trade-offs of neurological and hormonal functions, might be seen as the initial condition, or the core basis for how we respond to challenges and stressors from our environment.
Theoretically this theory proposes that throughout history we evolved working together in villages and communities. The core majority were a group of similar-minded individuals that could get along easily and keep the peace. They evolved to process and prioritize information for sociability. They were adept at imitation, following the crowd and working with others. Because we know from the work of Dr. Fisher and Dr. Michael Lesser that these personalities were dispersed in such a way as the periphery were the more rare personality types. More interested in things and tinkering, exploring, telling stories and taking up causes. These different groups, or personalities, processed information uniquely and had different priorities and motivations. They were innovators, explorers, protectors, leaders, scientists, geeks, artists and creatives (Lesser and Kapklein, 2003). These neurodiverse outliers processed and experienced the world very differently than the more sociable core. However, because of both the core and the diverse Peripheral Minds we thrived with each unique personality bringing value to cooperative goals (Bergmüller et al., 2010; Smaldino et al., 2013).
This diversity is stable across the world, as shown in personality and evolutionary studies (van Oers and Miller, 2010; Crespi, 2017; Quinn et al. 2016). Personality studies additionally inform us that these diverse groups are uniquely vulnerable to stress (Matthews, 2016). Personalities, or character traits, are shown to have unique genetic, neurobiological and neuroendocrine underpinnings. As described in studies linking serotonin, dopamine, testosterone and estrogen to both personality (Fisher 2015) and stress resiliency (Van Bodegom et al., 2017; Arnold et al., 2014; Boersman and Tamashiro, 2015; Boyce, 2016).
Thinking Types: Word, Picture and Pattern Thinkers
The idea that there are “thinking types” on the spectrum is discussed by Temple Grandin (Grandin, 2010; Quora in Forbes Online, 2017). Multiple Intelligences were also discussed by Howard Gardner in his 1983 “Frames of Mind” in which he discusses 9 types, with the strongest in three areas; Visual, Math and Language (Strauss in Washington Post, 2013). Gardner’s intelligence types are very similar to Temple Grandin’s: Picture, Pattern and Word Thinkers. These thinking types are informative for giving us distinctions in inherent wiring and unique approaches to processing information (Cerruti, 2013).
The Broader Autism Phenotype
Leo Kanner described the parents of those with autism as having “abstractions of a scientific, literary or artistic nature, limited in genuine interest in people” ( Kanner 1943)
Personality traits are known to be at the core of what is considered the “Broader Autism Phenotype” (BAP) (Landry and Chouinard, 2016). The BAP are family members who express milder characteristics and traits of autism (Losh et al., 2008; Billeci et al., 2016; Szatmari et al., 2008). Numerous studies document this constellation of subtle language, cognitive, social and personality characteristics that parallel the defining features of autism disorder and the BAP Ruparelia et al., 2017; Vukusic et al., 2016). The broader autism phenotype genes could also coordinate with greater or specific stress plasticity (Belsky et al., 2009; Henckens et al., 2016; Jensen, 2013). High rates of anxiety and mental illness are more common among parents and relatives, in both creative-types (Karpinski et al., 2017), the BAP and individuals with autism (Murphy et al., 2000; Jokiranta et al., 2015). The BAP may also be able to predict child functioning when that child tips into autism (Maxwell et al., 2013). For example, a child has more intense versions of sensory dysfunction when parents and siblings show sensory atypicality (Donaldson et al, 2017; Mayer, 2017; Glod et al., 2017). These studies are showing predictive patterns of traits which turn to disability, and this predictability may be mediated through stress mechanisms.
When considering the “what ifs” of autism and the BAP, “what if” these phenotypes are more sensitive because they are more evolutionarily adaptive and plastic?
Studies on the genetics of autism have suggested just this. That the genes involved in autism include signatures for both positive and negative selection (Shpigler et al., 2017). They are part of the essential genes we need to survive and thrive (Xiao et. al., 2016). Renato Polimanti of the Department of Psychiatry, Yale School of Medicine states: “Accordingly, at least two different evolutionary mechanisms appear to be present in relation to autism genetics: 1) rare disruptive alleles eliminated by purifying selection; 2) common alleles selected for their beneficial effects on cognitive skills. This scenario would explain autism prevalence, which is higher than that expected for a trait under purifying selection, as the evolutionary cost of polygenic adaptation related to cognitive ability” (Polimanti and Gelernter, 2017).
Genes for autism have likely evolved under complex evolutionary forces, and researchers describe this force leaving unique signatures on candidate genes (Tsur et al., 2016). Dr. Idan Menashe, along with his colleagues, Erez Tsur and Professor Michael Friger at the Department of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel “searched for evidence of positive selection in these genes, which would cause an increase in frequency until they are a factor in the population. What they found is while this kind of mechanism could explain the prevalence of autism in the human population; they found no indications of positive selection in autism as the disorder. They suspect that autism susceptibility mutations are in the human genome, but they only present as an autism disorder when combined with other genetic, non-genetic or environmental factors”.
Bernard Crespi, professor of evolutionary biology at Simon Fraser University and one of the initiators of the imprinted brain theory discusses in “Autism as a Disorder of High Intelligence” that the paradox of autism can be resolved under the hypothesis that autism etiology commonly involves enhanced, but imbalanced, components of intelligence. “This hypothesis is supported by evidence showing that autism and high IQ share a diverse set of convergent correlates, including large brain size, fast brain growth, increased sensory and visual-spatial abilities, enhanced synaptic functions, increased attentional focus, high socioeconomic status, more deliberative decision-making, profession and occupational interests in engineering and physical sciences, and high levels of positive assortative mating. These findings help to provide an evolutionary basis to understanding autism risk as underlain in part by dysregulation of intelligence, a core human-specific adaptation. In turn, integration of studies on intelligence with studies of autism should provide novel insights into the neurological and genetic causes of high mental abilities, with important implications for cognitive enhancement, artificial intelligence, the relationship of autism with schizophrenia, and the treatment of both autism and intellectual disability” (Crespi, 2016).
Neurogeneticist Christopher A. Walsh, a HMS Bullard Professor of Pediatrics and Neurology at Boston Children’s, found that animal models with intensive environmental stimulation can increase gene expression and that this type of stress may be a main driver of behavioral evolution. Michal Dubovicky’s work on toxicology and the neurobehavioral manifestations of developmental impairment states that: ”Individual characteristics of human nature (e.g. introversion, extroversion, mood, activity, adaptability, aggressiveness, social ability, anxiety) do not need to be primarily innate. They can be determined by the action of various influences and their interactions on functional development of the brain. There is ample epidemiological and experimental evidence that chemical and/or physical factors acting during sensitive time windows of the brain development can cause mental, behavioral, emotional and/or cognitive disorders. Environmental pollutants, addictive substances, drugs, malnutrition, excessive stress and/or hypoxia-ischemia were reported to induce functional maldevelopment of the brain with consequent neurobehavioral disorders” (Dubovický, 2010). “Walsh has also noted in his work that the intensive training often helpful for children on the autism spectrum mean that these genes can be addressed during life. That the noncoding sequences control levels of gene expression can change, suggesting that a lot of the gene in autism is good—if we can find ways to manipulate it, turn it back on” (Fliesler in Harvard Review “Autism and Evolution”, 2016; Doan et al., 2016).
Autism as a platform has the potential to teach us quite a lot about stress and evolution. What happens, both positive and negative, to our minds and interrelated systems when we stress our diversity of talents and thinking types. And the answer could be a gateway to new understandings of human behavior, potential and limitations. In a recent 2016 paper in Scientific America by science writer and computational biologist Jim Kozubek, new research from CRISPR (gene editing technology) has currently led us to the conclusion that “there are no superior genes, only genes that provide advantages with a tradeoff for other disadvantages” (Kozubek in Scientific American, 2016)
How is Stress Programmed?
A relatively new discovery in science is having a profound impact on autism research. Transgenerational epigenetics or ancestral programming is the idea that what happens to parents or grandparents can be passed down to children and grandchildren (Hurley in Discover Magazine, 2015). Evidence has shown that environmental factors that alter a person’s phenotype, can have this type of cross-generational impact. This is theoretically meant to enable an offspring to better survive in adverse environments (Vaiserman et al., 2017; Johnson, 2017). They receive the information of the generation before from the stresses they experiences. It is embedded and communicates with their DNA turning switches on or off (Hunter et al., 2015; Yuen et al., 2017). This type of complex relationship with the environment is best described within the scientific model of Complexity or Complex Systems (Plsek and Greenhalgh, 2010; Randolph-Gips and Srinivasan, 2012)
This is a paradigm-shifting concept realized in just the past decade. That Charles Darwin, the father of evolution, would have to now share the stage with his competing theorist, John-Baptiste Lamarck. Darwin had thought we changed only through random mutation, and Lamarck thought we changed according to our environmental needs and influences. For hundreds of years Darwin was our only consideration, now we know that we need to blend these two theories together.
Since genetic and environmental factors are both involved in autism (Karimi et al., 2017), and there are multiple mechanisms of gene and environment interactions required to delineate its development (Koufaris and Sismani, 2015), an epigenetic understanding is essential for understanding autism (Loke et al., 2015).
Epigenetics and Stress
Stress mechanics are epigenetic mechanisms. Stress is the way we communicate with the environment. We know that most remodeling and communication with the DNA is done through stress communication of needs (Babenko et al., 2015; Daskalakis et al., 2013). Stress is the language in which we adapt to the environment (Goldani et al., 2014) and the integration of epigenetics in the emergence of autism is revolutionizing the way we think about it (Hamza et al., 2017; Nardon and Elliot, 2016).
Bruce McEwen, an expert in stress neuroendocrinology who runs the Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology at Rockefeller University, describes how epigenetics are the manner in which stress communicates. In his July 2017 article in Aeon Magazine he states that: “Epigenetics drives the seamless integration of experiences, both good and bad, acting on our genetic code over our life course. We now understand that epigenetics is the means by which stress acts on the body, the genome, and the brain… the hormones did not work alone and required, among other mediators, the main neurotransmitter in the brain, glutamate. Thus, circulating hormones not only enter the brain and bind to receptors but also participate with the brain’s own neurotransmitters in what we now call ‘adaptive plasticity’ – structural changes in the brain to enhance our success and survival. Adaptive plasticity underlies behavioural and neurological adaptation to the world. For example, shrinkage of dendrites in the hippocampus protects those neurons from damage by over-stimulation during toxic stress. The brain is the central organ for adaptation to experiences, including stressors, which are capable of changing brain architecture as well as altering systemic function through neuroendocrine, autonomic, immune, and metabolic systems. Because the brain is the master regulator of these systems, as well as of behavior, alterations in brain function by chronic stress can have direct and indirect effects on cumulative allostatic overload, which refers to the cost of adaptation. There is much new knowledge on the neural control of systemic physiology and the feedback actions of physiologic mediators of brain regions regulating higher cognitive function, emotional regulation, and self-regulation. The healthy brain has a considerable capacity for resilience, based upon its ability to respond to interventions designed to open “windows of plasticity” and redirect its function toward better health. As a result, plasticity-facilitating treatments should be given within the framework of a positive behavioral intervention; negative experiences during this window may even make matters worse. Indeed, there are no magic bullets and drugs cannot substitute for targeted interventions that help an individual become resilient.” (McEwen, 2016; McEwen in Aeon, 2017).
Dennis Grayson, Professor of Molecular Neuroscience at the University of Chicago Psychiatry Department, describes the crossroads of epigenetics and autism thusly: “Genetic research has identified large numbers of genes that contribute to autism phenotypes. There is compelling evidence that environmental factors contribute to autism through influences that differentially impact the brain through epigenetic mechanisms. Both genetic mutations and epigenetic influences alter gene expression in different cell types of the brain. Mutations impact the expression of large numbers of genes and also have downstream consequences depending on specific pathways associated with the mutation. Environmental factors impact the expression of sets of genes by altering methylation/hydroxymethylation patterns, local histone modification patterns, and chromatin remodeling.” (Grayson and Guidotti, 2016).
What has made Stress more Stressful?
Deficiencies that increase Susceptibility
Nutrition encompasses many aspects of our growth and success. Problems are created when they are deficient, in excess or out of context. This includes adequate calories and a sufficient supply of nutrients (Ballard and Youngson, 2015). In a stress context, there are three deficiencies in particular that greatly impact our homeostatic and ecosystem resilience. These three modulators have also been compromised significantly in the last century and are seen consistently associated with many diseases and disorders, even if their involvement has not yet been fully understood.
John Sterman Director of MIT Systems Group in his 2002 seminal speech “All Models are Wrong: Reflections on becoming a systems scientist” (Sterman, 2002) stated:
“Thoughtful leaders increasingly recognize that we are not only failing to solve the persistent problems we face but are in fact causing them.”
“Revelations about the role of the human microbiome in our lives have begun to shake the foundations of medicine and nutrition” (Scientific American Grogen, 2015)
Cecil Lewis, professor of Anthropology at the University of Oklahoma, discusses that our microbiota have changed drastically in the last 100 years (Tito et al., 2012). “Our rural -cousins resemble our ancestors more than city-dwellers.” Maintaining this relationship and diversity appears of the utmost importance, especially for our ability to handle, detect and respond to our environment, foods, and stressors (De Filippo et al., 2010).
The gut microbiota influences development and behavior through the neuroendocrine, neuroimmune, central, peripheral (Orefice et al., 2016; Foster et al., 2016) and autonomic nervous systems (Felice and O’Mahoney, 2017). This interaction is bidirectional and known as the brain-gut axis (Li et al., 2017). It is becoming more and more likely to be one of the major interfaces between environmental and genetic risk factors that are associated with autism (Vuong and Hsiao, 2017). An abnormal gut microbiota is associated with many diseases, including autism (Kelly et al., 2017).
Our microbiomes have evolved with us and we have evolved because of them (Gibbons, 2016). Our relationship with our microbiome is showing just how beneficial and necessary they are to us. These microbes have tremendous potential to impact our physiology, both in health and in disease. They contribute metabolic functions, protect against pathogens, educate the immune system, and, through these basic functions, directly or indirectly affect most of our physiologic functions (Shreiner et al., 2016). The importance of the gut–brain axis in regulating stress-related responses has long been appreciated. More recently, the microbiota has emerged as a key player in the control of this axis, especially during conditions of stress provoked by real or perceived homeostatic challenge (Foster et al., 2017).
Fatty Acid Deficiencies
In 1911 Procter and Gamble introduced, what was considered at the time, a healthy alternative to animal fats, Crisco or hydrogenated vegetable oil. We now know these trans-fats were one of the worst decisions in history for our health. And while they were banned in the United States in 2013 (to be fully enacted by 2018), the pervasive effects of trans-fats doesn’t stop with removing them. Although a study investigating heart attacks have shown that this decision has already been a lifesaving one, with cardiovascular events in New York down 6.2% (Brandt et al., 2017), trans-fats may be a continued threat to our brains (Ginter and Simko, 2016), nervous systems and transgenerational cognitive development. Trans-fats likely had a much more devious impact, such as lowering our threshold for stress (De Paula Simino et al., 2017; Mennitti et al., 2015; Bradbury, 2011; Zárate et al., 2017; Lindsay et al., 2017) and impacting programming issues across several generations (Innis 2011; Pase 2017).
Fatty acids from fish and animals were likely a very important part of our evolution (Bradbury, 2011) and their absence in our diet could be impacting autism susceptibility. Jolien Steenweg-de Graaff, a Postdoctoral Researcher at Erasmus MC, suggest a biological pathway between maternal fatty acid intake during pregnancy and autistic traits in the offspring (Steenweg-de Graaf et al., 2016). Biomarkers for fatty acids and autism have been suggested by researchers in Saudi Arabia (El-Ansary et al., 2011) and New Zealand (Mazahery et al., 2017). Interventions with fatty acids are making interesting headway and are a continued avenue of suggested treatments options (Fortunato et al., 2017; Yui et al., 2016).
Sunlight Deficiencies: Circadian Unbalanced
Whether a stress like the sun and UV radiation creates enough genetic and cellular stress on the skin to create cancer depends on many factors. Genetics, skin type, duration of exposure, previous exposure, nutritional status, medications, and even psychological and genetic stress levels (Sinnya and De’Ambrosis, 2013) can impact how sun exposure leads to skin cancer (Gillberg et al., 2017). While there can be dangers the sun also brings us vital ingredient to our health and well being. There are three nutrients discovered so far that are involved in stress regulation and autism from the sun; Melatonin (Tain et al., 2017), Vitamin D (Frei et al., 2015; Kočovská et al., 2017; Vuillermot et al., 2017; Mazahery et al., 2016) and Nitric Oxide (Fleury et al., 2017; Yui et al., 2016).
Melatonin has been long associated with autism (Tordjman et al., 2013; Pagan et al., 2014). Stress dysregulation of genetic pathways that synthesize or metabolize serotonin, melatonin (Veatch et al., 2015) or cholesterol (Gillberg et al., 2017) is a more likely mechanism than a direct deficiency of sunlight per se. However, exposure to sunlight and the experience of autism may disrupt this very important relationship of natural energy distribution and recovery rhythms. Circadian rhythm disruption in mothers, whether by avoiding the sun, too much artificial lighting (Smolensky et al., 2015; Smarr et al., 2017) or prenatal stress disruption may be a part of autism through its role in stress adaptation distress and impaired resilience.
What causes Cellular Stress?
Early Life Stress
While genetics, personality, brain thinking-type, gender, deficiencies and nutrition (Moody et al., 2017) influence how we respond and adapt to stress, there are then the stressors themselves. Environmental stressors that are said to contribute to an autism diagnosis include; various pharmaceuticals (Ornoy et al., 2016; Mezzacappa et al., 2017), chemicals from pollutants (Boggess et al., 2016; Weisskopf et al., 2015; Dunaway et al., 2016), industrial exposures (Bolton et al., 2017), noise pollution (Molina et al., 2016; Jafari et al., 2017), pesticide exposure (De Felice et al., 2016), heavy metals (Arora et al., 2017 via National Institute of Health), viruses, infections (Jiang et al., 2016) with fever (Lombardo et al., 2017; Wong and Hoeffer, 2017), endocrine disruptors (Stein et al., 2015), physical and emotional traumas (Fujiwara et al., 2016; Tran and Miyake, 2017), father’s age (Janecka et al., 2017), the mother’s health (Kosidou et al., 2016; Madore et al, 2016) or the mother experiencing social/emotional stress (Varcin et al., 2017). Activation of inflammatory pathways (Bilbo et al., 2017) during pregnancy or shortly after birth and infant neglect (Nelson in Spectrum News, 2017 ) are also implicated.
“Early Life Stress” (Provençal and Binder, 2015), the impact of stresses early in life, can change the response to stress exposures in later life (Picci and Scherf, 2015; Daskalakis et al., 2015; Faraji et al., 2017). They alter our trajectories in such a way as to be involved in later life outcomes (Chen and Baram, 2016). This can alter gene expression and permanently affect the structure and function of the architecture of the brain and body (Lahiri et al., 2013; Wen and Herbert, 2017) and create outcomes that are often not considered as having such complex origins. These early life impacts can influence later outcomes such as later life depression, seizures and obesity (Daskalakis et al., 2015; Cottrell and Seckl, 2009; Huang, 2014; Hiramatsu et al., 2017).
Studies have shown that many cases of autism likely begin in the womb (Stoner et al., 2014). The combined impacts of susceptible genetics, traits, deficiencies, ancestral stress and early life stressors may all be part of what creates individuals with overly activated systems.
Purinergic Stress Signalling Pathway
Dr. Robert Naviaux, professor of genetics in the departments of medicine, pediatrics and pathology of the University of California San Diego discusses that Purinergic signaling is the very cellular-most level signaling of a response to stress. There are of course many interconnected pathways in which stress could lead to autism. Including the amygdala (Anderson and Maes, 2014), the Hypothalamic-Pituitary-Adrenal (HPA) axis (Taylor and Corbett, 2014), Brain-derived neurotrophic factor (BDNF) (Al-Ayadhi, 2012), oxytocin (Alanazi et al., 2017), mTOR (Sengupta et al., 2010; Yui et al., 2015; Onore et al., 2017), glutamate signalling (El-Ansary, 2016) and any number of susceptible genes that are connected to stress signalling (Hunter et al., 2010). According to Dr. Naviaux’ “Cell Danger Response” theory, autism can result when a stress during early brain development triggers a chronic danger response. He suggests that stress that starts this chain of events can come from an environmental influence, a genetic problem or a combination of both. He suspects that the result is chronic brain inflammation and frayed connections between brain cells (Naviaux et al., 2017).
RAS Stress Signalling Pathway
Alan Packer, a senior scientist and geneticist at the Simons Foundation, suggests that the evidence implicating RAS signaling in autism comes both from the functional studies of individual genes and from comparisons between autism and syndromes known to be caused by hyperactivation of the RAS pathway. He states that “An impressive series of discoveries over the past decade has shown that this group of related developmental disorders is characterized by mutations in different genes in the RAS pathway, each of which results in a gain-of-function of ERK signaling. Thomas Bourgeron discusses the genetic architecture of autism with a similar view in mind, by arguing that mutations that disrupt synaptic homeostasis might be well or poorly tolerated depending on the genetic buffering capacity of the individual. In other words, particular genetic backgrounds may be more vulnerable to mutations (or environmental factors) that perturb neural function through the modulation of synaptic strength.”
Ya Wen and Martha Herbert at Harvard University have expressed the idea that autism-associated genes may contribute not only to core features of autism themselves but also vulnerability to other chronic and systemic problems. Autisms may thus arise, or emerge, from underlying vulnerabilities related to pleiotropic genes associated with pervasively important molecular mechanisms, vulnerability to environmental input and multiple systemic comorbidities (Wen et al., 2016).
Later Life Stress
“According to Andreasen, our openness to new experiences, tolerance for ambiguity, and the way we approach life enables us to perceive things in a fresh and novel way. Less creative types “quickly respond to situations based on what they have been told by people in authority”, while creatives live in a more fluid and nebulous (read: incredibly stressful) world.” (Dr. Susan Biali in Psychology Today, Biali, 2012)
Once there is an adaptation of the various stress mechanics of the human body, individuals with autism may be more susceptible to daily stressors (Maine et al., 2013; Faraji et al., 2017). While we typically think of stress as social, and social stress is an important factor (Kushki et al., 2013; Levine et al., 2012; Wells et al., 2017), stress is also the various ways the body needs to maintain homeostasis (Corbett et al., 2009). Stress balancing issues come from regulating sleep (Sengupta et al., 2010; Fliesler in Vector, 2016; Lipton et al., 2017), body temperature, immune function (Meltzer and Van de Water, 2017; Lombardo et al., 2017), mitochondrial/metabolic functions (Griffiths and Levy, 2017; Bu et al., 2017), food sensitivities (Stafford et al., 2017; Ly et al., 2017), fear regulation (Sharp, 2017), proneness to feeling shame (Davidson et al., 2017; McCarthy-Jones, 2017), pain regulation (both hyper and hypo) (Fitzgibbon et al., 2013; Yasuda et al., 2016), proprioception (Riquelme et al., 2016), alexithymia, interoception (Shah et al., 2016) and of course sensory atypicality (Qasem et al., 2016) that creates oxidative stress from lights, sounds and touch (Corbett et al., 2016; Wigham et al., 2015).
While all teenagers face challenges during developmental growth periods, kids with autism have it especially difficult. They face unique challenges because of amplified or altered stress reactivity (Taylor and Gotham, 2016). The Broader Phenotype or personalities of artists, scientists, leaders (Overskeid, 2016) and creatives are suspected to already be naturally experiencing internal and social stresses at greater levels (Andreasen, 2008; Ingersoll and Hambrick, 2010). And researchers such as Blythe Corbett at Vanderbilt University have shown that having autism can multiply these socioemotional challenges (Corbett and Simon, 2014; Corbett et al., 2016). Corbett expresses in studies that those with autism show “higher physiological arousal during play associated with heightened sensory sensitivity and a pattern of increased stress in various contexts.” A lowered executive function capability has also been shown to increase perception and impact of social and physical stress (Shields et al., 2017). This can create higher risk and more susceptibility during growth and developmental stages. As age, gender and genetic profiles can shape the way we respond to stress (Novias et al., 2017).
Autisms are suggested to have higher rates of comorbidly occurring conditions (Pisula et al., 2016; Cawthorpe, 2017). If we see autism as a stress adaptation with increased sensitivity, greater allostatic loads, and impaired ability to handle stressors. And if comorbidities are the result of excessive oxidative stress, than having autism (Orinstein et al., 2015) would theoretically increase the risk of having comorbid conditions (Diaz-Beltran et al., 2017). It is likely that those with autism react to negative life events differently or with greater intensity than individuals from the general population. The early life programming and later life environment would be considerable influencers in the expression of psychiatric comorbidities in the autistic individual (Mazzone et al., 2013). Individuals with autism may run a higher risk of co-occurring and comorbid conditions, such as anxiety, depression and schizophrenia (Smaga et al., 2015).
Neurodiversity: the Positive Side of Autism and Stress Enhancements
One of the biggest problems facing those with autism isn’t necessarily living in an amplified world. In fact many autistics embrace this quality of enhanced perception. Qualities like perfect pitch (Dohn, A. et al. 2012), creative abilities (Chamberlain et al., 2013; Kasirer and Mashal. 2014), enhanced logic and divergent thinking (Best et al., 2015). The additional information sometimes crisscrosses senses creating synesthesia (Ward et al., 2017) and opportunities for unique perspectives. It is also suggested that coping measures may enhance thinking and learning styles, such as thought processes described by Temple Grandin (Grandin, 2009), job and interest strengths described by Timo Lorenz and Kathrin Heinitz (Lorenz and Heinitz, 2014) and LUT and INT learning styles described by Ning Qian and Richard M. Lipkin (Qian and Lipkin, 2015). The problem lies that this sensitivity has a greater potential to lead to more comorbid conditions that cause considerable harm. Oxidative stress likely influences the severity (Meguid et al., 2017) of autism symptoms, potential regressions (Hoover, 2015), “autistic exhaustion” and the co-morbid manifestations, which often become more apparent during these life transitions.
These co-occurring and co-morbid physical and mental health conditions have been associated with suicide rates (Takara and Kondo, 2014) and impaired quality of life for those on the spectrum. Understanding this combination of priming and programming could be helpful for devising future intervention and treatments.
What are the Manifestations of Stress in Autism?
As an adult with autism, the one feature I would say describes my experience of autism most is that I take in “too much information”. It is the outstanding feature I experience and one that seems to be connected to all of my other symptoms; an amplified and heightened sensory experience of the world. For me, it seems elementary that this could be created by stress and since stress doesn’t act alone (it has to act on something), it seems reasonable that this acted upon a unique sensory experience of the world or the BAP within me to begin with. Stress merely amplified and ultimately discombobulated that experience. But because of the way stress can up or down regulate, excite or suppress and because stress has many adaptation strategies, we get many opposites and variations of patterns and interconnected disorders and diseases.
The three core features of autism are 1) Restrictive and Repetitive Behaviors and Interests (RRBI), 2) Social Communication Difficulties, and 3) Atypical Sensory experiences. Core features may manifest for different reasons, but these behaviors may illuminate the compensation patterns of experience of amplified stress adaptation in autism.
Restricted and Repetitive Behaviors and Interests (RRBI)
Repetitive behaviors include features such as pacing, stimming, routines, lining things up and need for sameness. RRBIs are considered a core feature found in everyone on the spectrum. Atypical sensory experience has been suggested to be associated with RRBI (Wolff et al., 2017), and unique sensory experience by 90-95% of the autism population (Elwin et al., 2016). As is typical with autisms, there are likely multiple functioning channels as to why this may occur. Over and under-activation of various brain regions can lead to these behavioral outcomes. The re-regulation of the cortical stratum (Kim, 2016) by stress (Vogel et al, 2016) is one such example. Stress can also create an energy depletion in the mitochondrial (Napoli et al., 2013) that could lead to these behaviors.
It is suggested that some with autism see every situation as a new experience (Gaigg, 2012). That those with autism live only “in the moment”, because of the large input of sensory information (Haker et al., 2016). This overwhelming experience may lead to the need for sameness and predictability (Van de Cruys et al., 2015). A theory proposed by researchers Pawan Sinha, Margaret Kjelgaard and Annie Cardinaux suggest that those with autism live in a “Magical World” of unpredictability, as a consequence of this sensory overload (Sinha, Kjelgaard and Cardinaux in Spectrum 2015). Many people on the spectrum themselves say that RRBI behaviors are soothing, relieve anxiety and reduce fear and feelings of stress (Rodgers 2016; Joyce et al., 2017; Uljarević et al., 2017; Weiss et al., 2014). Structural aspects (Kim et al., 2016) for RRBI are also known to be mediated through stress impacts (Sesack and Grace, 2009) and adaptations.
Self-stimulating behaviors (commonly referred to as “stimming”) are suspected to be performed by those with autism (Kirby et al., 2017) for reasons that are consistent with the idea that there is hyper/hypo-functioning, or up/down regulation of stress sensitivity. There are those on the spectrum who stim to relax and there are those on the spectrum who stim to stimulate (McCormick et al., 2016). There are also behaviors like self-injury that may be a disruption of pain perception and the need to “block” pain (Bunderla and Kumperščak, 2015; Klabunde et al., 2015). While the autisms themselves may be strikingly different, it could be that all three of core deficits come from sensory overwhelm and the compensatory behaviors in response to heightened stress reactivity.
When Stress Pushes Past Core Symptoms
Not everyone with autism experiences negative co-morbid conditions or are actively experiencing side effects of heightened oxidative stress. In many ways, there are those with autism that have found a new homeostasis, thresholds have shifted and while amplified they have relatively stabilized. They have found a balance within themselves and may be operating at a level that is fine or comfortable for them. They may be using core features (RRBIs, avoiding eye contact, stimming, additional supports) to maintain their own internal balances. This is likely one reason it could be detrimental to attempt to “train” the core symptoms out of the autistic. The ABA of the 1980’s shortcomings likely came from this mistaken belief that if they could punish or reward these behaviors, and hence reverse or remove them, this would be improving autism (Epstein et al., 1985). However, those behaviors may have been what was helping them maintain internal homeostasis. Those behaviors likely helped to reduce internal stress. And a large reason for the continued controversy and civil rights movement of autistics that claim, and likely rightly so, that those behaviors, when properly directed and not indicating larger issues, are not only fine but necessary.
Overlapping and CoMorbid Conditions
Using a stress perspective lens we see “variations on the same tune” created by stress. While the core symptoms of autism may be ways individuals attempt to manage stress, the co-occurring conditions may represent unchecked stress. (The following is meant as an example and not an exhaustive list of comorbid and overlapping conditions)
Aggression is considered one of the most problematic issues on the spectrum (Fitzpatrick et al., 2017) with prevalence rates varying from 10-68%. While it is often assumed that aggression comes from not being able to communicate feelings, wants and desires, other factors are likely heavy influencers (De Giacomo et al., 2016). Such as the struggles with emotions from alexithymia (Velotti et al., 2016), working memory and brain energy constraints (Li-Byarlay et al., 2014), fight or flight from sensory overload (Ziermans et al., 2012), executive function, (Hecht and Latzman, 2017; Schoorl et al., 2017), sleep and associated problems of ADHD (Chen et al., 2017), oxidative stress (Coccaro et al., 2016), rumination or obsessive worry and fear (Buades-Rotger et al., 2016) and the struggles with integrating sensory information inducing panic (Limmer et al., 2015; Emmerling et al., 2016).
Connie Anderson, Ph.D. of the IAN Community Scientific Liaison at the Kennedy Krieger Institute, states that “typical children use aggression to achieve social goals, such as getting attention or avoiding adults’ demands. In autism aggression, it is typically about sensory overload (Duerden et al., 2012), having a soothing object or pattern taken away, an interruption of a repetitive behavior, or when trying to escape overwhelming or uncomfortable sensory or emotional input.”(Anderson in IAN, 2012).
Gastrointestinal Distress (GI) symptoms in children with autism have had suggested prevalence ranges from 23% to 70% (Chaidez et al., 2015). GI function is also suggested to be closely related, bidirectionally, to autism severity. Prenatal impacts are shown to be related to dysbiosis of the gut microbiota, which can create alterations in metabolism and serotonin production (Lim et al., 2017). Brad Ferguson, PhD, postdoctoral research fellow in the Department of Radiology at the MU School of Medicine and the MU Thompson Center for Autism and Neurodevelopmental Disorders identified a relationship between increased cortisol response to stress and gastrointestinal symptoms in people with autism spectrum disorder (Ferguson et al., 2017). This bidirectional relationship, that the gut impacts the brain and the brain impacts the gut, is found in many studies. Chronically activated stress signaling in IBS is suggested to maintain a proinflammatory state, not only in the gut but in the rest of the brain and body. Some of these inflammatory factors are suggested to migrate to the brain during stress, inducing regional neuroinflammation.
These alterations may play an important role in heightened sensitivity and pain in IBS (Icenhour et al., 2017). While the true relationship between atypical sensory experience and IBS symptoms has yet to be fully understood, a relationship is most assuredly there. Interestingly enough, reviews of autism and GI issues have also seen a connection of gut issues to sleep issues (Klukowski et al., 2015; Prosperi et al., 2017) and that this hyper-response to pain is connected to experiences of early life stress (Holschneider et al., 2016).
A significant proportion of children with autism have comorbid sleep disorders. Parental reports suggest that over 68% see sleep as highly problematic. Other studies suggest that over 75% of those on the spectrum have sleep disturbance (Aathira et al., 2017). Comorbidities associated with autism, such as ADHD and mood disorders, as well as medications used to treat these comorbidities, often have effects on sleep architecture (Maxwell-Horn and Malow, 2017) with stress and sleep having a bidirectional relationship (Hirotsu et al., 2015; Bailey and Silver, 2014). Research into circadian rhythms and sleep regulation includes the BMAL1 gene (Francey and Hogenesch, 2017) and mTOR activation (Fliesler in Vector, 2015; Lipton et al., 2017; Nicolaides et al., 2015; Goeffray et al., 2017). These seem interesting lines of research for future studies on the interaction of sleep, stress and autism.
David Ginty, a professor of neurobiology at Harvard Medical School says in an article in Japan Times by Rowan Hooper that “One way of thinking about what is causing this behavior in the mice is that they have a problem with the “volume control” in their peripheral sensory neurons. What this means, says Lauren Orefice, a colleague of Ginty’s, is that the volume is turned up all the way in these neurons, leading the animals to feel touch at an exaggerated, heightened level.” (Hooper in Japan Times, 2017; Orefice et al., 2016; Kaiser et al., 2015; Riquelme et al., 2016). Simon Baron-Cohen, a well-known autism researcher at Cambridge University in Britain calls this “sensory hypersensitivity.” For children with autism, their bodies are on constant red alert for irritations, which can be triggered by touch and the feeling of clothes that neurotypicals tolerate without a thought. Since this does not seem to be purely genetic, the researchers suggest that there is a “window of vulnerability” where this volume gets turned up (Baron-Cohen, 2006).
Researcher Francis McGlone has discovered a potentially vital role of touch sensitivity for affective (emotionally sensing) touch and autism (McGlone et al., 2014). This is the type of very light touch that many with autism find unnerving. Called CT Fibers they trigger part of the brain that is implicated in autism. They are fibers deep in the limbic system circuits that process emotion. The same brain structures implicated in autism sensory dysregulation can also be re-regulated by prenatal stress (Qui et al., 2015; Kolb and Gibb, 2015).
It is being suggested that this type of miswiring, potentially from over-active stress modifications, could be what is keeping some of those with autism from feeling socially connected to their caregivers. Touch that is supposed to be soothing is instead being felt as uncomfortable or even threatening.
William Singletary, President of the Board of the Margaret S. Mahler Psychiatric Research Foundation, has suggested that touch is an important part of reducing stress early in life. This lost ability because of amplified sensory activity could be a loss of a precious resource, affective touch, connection and confidence (reducing stress) given from a caregiver. This layered on stress amplification of something that should reduce stress (touch) now causing stress could manifest ever more issues (Uvnäs-Moberg et al., 2014; Singletary, 2016). More astoundingly, researchers like Singletary are creating what he thinks, and has so far shown, successful intervention models that help those with autism feel more connected and thus reducing stress, comorbid disorders and improving outcomes (Singletary and Zellner, 2017).
Seizures are suggested to be present in 20-30% with autism (Spence and Schneider, 2009). Autism and seizures are associated through various neurochemicals, genes (Bozzi and Borelli, 2013; Richerson and Buchanan, 2011; Svob Strac et al., 2016; Kudin et al., 2017; Carmona-Aparicio et al., 2015; Magdalon et al., 2017; Myers and Mefford, 2015) and environmental influences that create stress programming (Martinc et al., 2012; Shin et al., 2011; Koe et al., 2009; Desgent et al., 2012). Epilepsy’s connection to autism is presumed to be that both are conditions of a dysfunctional nervous system and an imbalance of excitation/inhibition (Bozzi et al., 2017). More individuals with autism have intractable epilepsy and there is a greater risk of death for those on the spectrum when they have epilepsy.
It is my hope that this Proof of Concept demonstrates that autism is best viewed as a stress adaptation. Autism through the lens of stress and chaos dynamics could resolve controversies and contradictions of the vastly different theories and explanations of autism.
The past avoidance of applying stress to diseases and conditions is partly because we saw stress as a single variable instead of an entire framework unto itself. And partly because the idea of stress seemed so chaotic that any discussion of it as a causative factor lacked meaningful discourse. Doctors often abused the term “it’s just stress” to mean that it was just something imagined or caused by anxiety in the patient and only within their own control, akin to “hysteria”. With the initial conditions we now have the key to make sense of the chaos. It gives us a new model and a new way to produce predictability and the beginnings to using a stress paradigm to understand disease.
It is my hope that researchers will continue to challenge, refine and build this initial model, integrating an overarching story and finding new solutions to help optimize autism for those on the spectrum.