Autism Spectrum Disorders: General Information

Autism spectrum disorders are a lifelong family of conditions involving extreme behaviors and social impairment caused by subtle changes in certain areas of the brain. Originally occurring in one in 10,000 in the 1950s, currently approximately one in 68 persons is diagnosed as having autism and the number is growing. The exact biological causes of autism and related developmental disorders are unknown, and will prove to be a major challenge to society. Despite the absence of any major brain malformations, studies have recently observed subtle changes in certain areas of the brain of patients with autism, including mild brain enlargement, nerve cell to nerve cell connections (synapses) and, interestingly, inflammation, which appear to occur largely during early brain development, but also throughout the life of the individual. Genetic (inherited) factors, or exposure of the developing fetal or newborn brain to some environmental toxin or infection may be a cause or contributor of these abnormalities. The insult may also worsen throughout life, as the person is continually exposed to such environmental factors at critical stages of brain development, or amongst individuals with impaired ability to break down these toxins.

In the normal brain these areas, collectively known as the limbic system, are involved in such complex activities as finding meaning in sensory experience and perception, social behavior, having certain interests, as well as emotions and memory recall. The limbic system is also involved in the control of complex habitual movement, from learning to dress and wash to performing in a musical symphony. Limbic structures are thus involved in such diverse processes from artistic creativity, learning a skill, self-care, recognizing a person's face, emotional bonding and the rearing of children, aggression and drug addiction. Thus abnormalities in these brain areas cut off or provide distorted impressions of reality for the person, leading to an inability to effectively relate to the world around him or her, and the person retreats to a world of social isolation. Persons with autism are trapped in a world of ritualistic behavior, urges, compulsions and self injury, coupled with drastically impaired ability to interact with those around them. Although most persons with autism exhibit profound disability, a select few show remarkable ability to perform certain skills, from playing a piano, or performing complex mathematical calculations, while at the same time, cannot feed or dress themselves or colour within the lines. Many have bizarre cravings for specific foods. The lifelong impairment to the person with autism is underappreciated and enormous, the emotional toll to the family is devastating, and the cost of our already strained public health care system to look after these persons throughout their lives is immense.

The behavioral and biochemical aspects of autism resemble disorders such as anxiety and mood disorders, schizophrenia, epilepsy, obsessive compulsion disorder, eating disorders, and a number of rare pediatric neurological conditions. Disorders of brain chemistry, particularly involving the neurotransmitters dopamine, glutamate, serotonin and GABA, which play a major role in limbic system function and movement, have been implicated. Linkages to a number of genetic abnormalities responsible for brain development are under investigation, but at this stage only account to being the sole cause of a small sub set of autism spectrum cases. This, coupled with the marked increase of the condition, particularly in populations who have migrated to more industrialized societies (for example, Somalis), or have adopted a Western diet or lifestyle, points to some interaction between genetic and environmental factors.

Autism has many "whole body" biological changes, which many scientists now feel are not only associated with the condition, but may in fact cause or contribute to the condition. Many persons with autism also have epilepsy, often difficult to diagnose in this population, which may contribute to some of the behavioral impairments (rage, learning impairments). Recent discoveries suggest abnormalities in the digestive system (diarrhoea and constipation), and studies have shown that some patient's symptoms are changed by certain dietary factors, antibiotics, or hospitalization, possibly resulting in alterations of diverse bacterial populations in the digestive system.

These microbial populations, known as the microbiome, outnumber our human cells 10 to one, with 100 times more genetic material. The complex array of compounds they produce throughout the lifecycle have unappreciated effects on our health, including influencing brain function and behavior. Emerging evidence shows that the microbiome has broad effects on our immune function and energy production, which has links to many conditions, including autism. Furthermore, autism has family linkages to various inflammatory disorders, such as rheumatoid arthritis, and there is also recent evidence of an ongoing inflammatory processes in the autism- affected brain. Further evidence suggests autism may be a broad disorder of energy metabolism, involving the mitochondria, the energy storehouse of the cell, which greatly affects brain function because of the nervous system's high energy requirement. Interestingly, these compounds produced by gut bacteria have profound effects on both mitochondrial and immune function.

Collectively, this suggests alterations in gut function, energy production and the immune system via a variety of environmental factors, possibly stemming from chemicals produced by gut bacteria, that may contribute to autism and autism-associated behavior. It appears that these biological compounds, largely stemming from the digestive tract but also present in diet, are, either directly or indirectly, altering brain function at a variety of levels. This has profound implications in uncovering the cause of, autism spectrum disorders, their cause, identification, prevention, and treatment.

However, a unifying testable hypothesis for this devastating disorder which considers all of these observations had not been found. There was a need to develop evidence based partnerships from traditional (behavioral, genetic), and emerging (environmental, energy metabolism, immune, gut, microbes, nutrition) fields to better and more completely study autism spectrum disorders. Autism is clearly a disorder of behavior. Therefore, the detailed analysis of complex movement, both in the human condition and in experimental animal models was absolutely essential. A number of compounds contained in the diet, metabolic by-products of organisms found in the digestive system, known as short chain fatty acids, are known to have profound effects on brain development, immune and energy system function, and ultimately behavior.

Dr. Derrick MacFabe, an M.D. neuroscientist from the University of Western Ontario, London, Ontario, Canada, in 2003, initially brought together a multidisciplinary team, the Kilee Patchell-Evans Autism Research Group,(KPEARG) comprised of both clinical and basic science experts to study autism spectrum disorders at a number of levels from this approach. Among these were University of Western Ontario researchers Drs. Kaus-Peter Ossenkopp, Donald Peter Cain, Martin Kavaliers, and Fred Posssmayer, behavioral and biochemical scientists specializing in the effects of a variety of compounds on brain development and behavior. In addition to behavior, basic science mechanisms examining brain development, inflammation, energy/fat metabolism and electrical activity were concurrently performed, using a number of established and novel rodent models for autism, to attempt to link the disparate findings and theories of autism spectrum disorders..

Over the last decade, through our policy of open access and free sharing of data and expertise, the undertaking of the KPEARG has grown immensely worldwide. World clinical and basic science experts in gut microbes (Drs. Tore Midtvedt and Rochellys Diaz-Heijtz, Karolinska Institute, Sweden; Drs. Koen Venema, Maastricht University, Netherlands; Jonathan Swann, Imperial College UK), brain energy metabolism (Dr. Richard Frye, Arkansas Children's Institute), gene environment interactions (Drs. Bistra Nankova and Ed La Gamma New York Medical College), diet-microbe interactions (Drs. Mark Cannon and Bill Kabat, Northwestern University, Chicago), and inflammation (Dr. Morley Hollenberg, University of Calgary) have immensely contributed to the function of the Group.

This major undertaking would have been impossible without initial and continued generous philanthropic support and vision from "GoodLife Fitness" CEO David Patchell Evans, himself the father of daughter Kilee, a child with autism. The Kilee Patchell-Evans Autism Research Group (KPEARG) is honoured to bear her name.

For a historical review of the foundation of the KPEARG click here