A Best Practices Model for Treating Autism to Improve Optimal Outcomes:Behavioral/biomedical interventions implemented together
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BIOMEDICAL
A Best PrActices Model for treAting AutisM to iMProve oPtiMAl outcoMes:
By Lauren Underwood, PhD
Lauren Underwood, PhD, received her doctorate in biology from Tulane University. Following graduation, she was awarded an NIH Post-Doctoral Training Grant Fellowship in vision research. She is the parent of a child recovering from autism and a health educator/
biomedical consultant for families of autistic children. Dr. Underwood is a Senior Staff Scientist for SSAI, Inc. supporting NASA. She is a Center for Autism and Related Disorders (CARD) IRB board member and has appeared in many peer-reviewed journals.
Introduction Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by deficits in socialization and communication as well as by abnormal behaviors patterns (Rapin, 1997; Lord, et al., 2000; Volkmar and Pauls, 2003). While most children who develop autism show abnormalities related to one of these key areas during infancy, the indicators may not become obvious until sometime during the second year of life. Research indicates that approximately 30–50 percent of children with ASD have a period of normal development, followed by developmental regression, with a loss of acquired skills, including language. This occurs anywhere between 16 and 25 months (Lord, et al., 2004) with the loss of acquired language typically occurring between the ages 12 and 18 months (Shinnar, 2001). Currently, autism is defined as a psychiatric disorder, not as a medical condition, and it is often perceived as a genetically-based mental disorder. There is no medical test for autism; therefore, diagnosis is based on a combination of psychological testing, complete history, physical examination, neurologic examination, non-medical evaluations (e.g., Checklist for Autism in Toddlers, Autism Diagnostic Observation Schedule, Autism Diagnostic InterviewRevised), and direct assessment/ observations of the child’s social, language,
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and cognitive development (Johnson, 2007; Filipek, et al., 1999; Volkmar et al., 1999). During normal development, milestones (skills or age-specific tasks that most children acquire within a certain age range) are naturally attained without being taught. Neurotypically developing children learn social and communication skills from their environment and from the people around them. The developmental milestones include gross motor, fine motor, language, cognitive, and social skills. In particular, the first three years of a child’s life is a developmentally dynamic time. When the term “developmental delay” is used (commonly the first diagnosis given to a child on the autism spectrum during an early intervention assessment or by a developmental pediatrician since the diagnosis of autism is often not given until the age of 4 or 5) it refers to a delay in one or more of the expected developmental milestones. Generally, these delays are ongoing and result in an overall major delay in the whole developmental process. During the period when autism seems to emerge, many significant milestones are delayed or even missed, thereby affecting normal behavioral development. As a result, more and more abnormal behaviors begin to display. Individually, behavioral treatments like applied behavior analysis (ABA) as well as medically-related biomedical approaches
have helped provide effective treatment modalities for autism. However, to optimize outcomes, a best practices model that applies these interventions together provides the best possibility for successful outcomes. This approach incorporates behavioralbiomedical treatment as a complementary synergistic model. The role of behavioral interventions Due to missed developmental milestones, children with autism are less equipped to acquire skills from their environment. Thus, behavioral interventions play an integral role in treating these children by reducing negative behaviors and increasing normal behaviors. Research shows the sooner a delayed child gets behavioral intervention, the better their progress will be. Treatment approaches grounded in behavioral interventions like ABA are considered invaluable as therapeutic and educational interventions for these children. In general, this educational framework manipulates antecedents and consequences of behavior to teach new skills and eliminate maladaptive behaviors. In particular, ABA uses behavioral analytic methods to understand current maladaptive behaviors and to change unacceptable behaviors into adaptive, acceptable ones. ABA systematically breaks down a task, skill, or behavior and then teaches the steps in sequence so a child significantly improves
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social behaviors. (Sulzer-Azaroff and Mayer, 1991). The most common ABA intervention, discrete trial training, is what most people think of when referring to ABA. The discrete trial enables the learner to acquire complex skills and behaviors by mastering the subcomponents of the targeted skill. However, ABA is not just discrete trials, but a behavioral program of comprehensive interventions, involving multiple settings, situations, and day-to-day activities. ABA has been scientifically studied and demonstrated to be highly effective for reducing negative behaviors in autism and increasing socially acceptable behaviors (Jensen and Sinclair, 2002). Given the considerable successful outcomes of autism treatments based on behavioral interventions like ABA, it is easy to understand why ABA is a necessary treatment. Several decades of research have proven ABA’s effectiveness for many children with autism. Many have achieved the optimal outcome: everyday functioning that is indistinguishable from that of typically developing peers. As a result, treatment approaches grounded in ABA are now considered the instrumental therapeutic and educational interventions for children suffering from this disorder. In addition, there is also strong support for complementary therapies, such as speech, occupational, physical, and sensory integration. Why biomedical interventions are necessary Although the etiology of ASD remains under investigation, research suggests that there is a genetic predisposition, which can be multifactorial and/or variable in expression (Lord, 2000). Numerous genes have been implicated in the susceptibility of certain individuals to have this disorder. Research also shows that children with autism suffer from multiple medical conditions involving dysfunction in the central and peripheral nervous systems as well as in the gastrointestinal and immune systems (Van Gent, 1997). Recent study supports a biomedical etiology for autism. While researchers are still investigating exact biological or metabolic pathways, case studies based on practical applications of this research suggest that
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The underlying concept of the biomedical approach is that the behavioral symptoms which define autism may be—at least in part—related to the child’s medical conditions. When these illnesses are addressed, psychological symptoms will improve.
successful outcomes improve when comorbid conditions—such as digestive disorders, immune system dysregulation and/or neuroinflammation—are treated. Literature provides evidence that comorbid conditions occur in children with autism (Ming 2008). Comorbidity is the occurrence of two or more disorders in the same person at the same time. Interactions between the co-existing conditions can affect the course, prognosis, and treatment outcome of cases of autism spectrum disorder. If these conditions are not addressed, they can affect developmental outcomes in other educational and sensory-related interventions. Today, treatments that address comorbid medical conditions, often associated with the underlying physiological imbalances that contribute to ASD symptoms, are emerging. Consequently, many parents and practitioners use medically-based treatment options, including modified diet, supplementation, and detoxification protocols. These biomedical treatments look at the application of natural, biological, and physical sciences to medicine and can include any of the following: healthier diet, nutritional supplementation, immune system regulation, gastrointestinal regulation, and detoxification as medically indicated. The underlying concept of the biomedical approach is that the behavioral symptoms which define autism may be—at least in part—related to the child’s medical conditions. When these illnesses are addressed, psychological symptoms will improve. The best practices model suggests that, if indicated, biomedical interventions should be used to stabilize the child’s medical symptoms in addition to implementing behavioral therapy. As a result, the child can maximize his or her learning potential. Anecdotal cases now demonstrate successful outcomes with an acceleration of skill acquisition within therapy programs in which biomedical issues are also addressed and treated. The position of the American Academy of Pediatrics “The Pediatrician’s Role in the Diagnosis and Management of Autistic Spectrum Disorder in Children” published in 2001 by the American Academy of Pediatrics (AAP) discusses specific strategies, including early intervention, behavioral management, habilitative therapies (speech occupational, and physical therapy), and medical management (including nutritional supplements, elimination diet, IVIG, secretin, and chelation), auditory integration training, and facilitated communication. The paper states that “ ... pediatricians should approach alternative therapies openly and compassionately ... and being willing to support a trial of therapy in select situations, and in such situations, requiring clear treatment objectives and pre-testing and post-testing.” Given this AAP recommendation, it is the responsibility of health care providers to educate family members and to help children with ASD by treating these conditions. In particular, there are several specific systems of the body that are often affected, including the immune system, the gastrointestinal system, the nervous system, and associated metabolic pathways. In support of biomedical treatments Autism is a whole-body condition. The systems of the body were meant to work together in a harmonious and integrated fashion to maintain good health. But when there is pathology in one bodily system, it can cause problems to another system. Gastrointestinal system Horvath, Wakefield, and others (1999, 2000, 2002) have shown that gastrointestinal inflammation is common in autism, which may lead to increased intestinal permeability, potentially causing abnormal immunologic responses to food proteins or pathogens. Three studies by Jyonouchi, et al. (2002, 2005a, 2005b), found that children
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BIOMEDICAL
with autism had more hypersensitivity to food allergens than did neurotypical children. These allergens are likely to cause gastrointestinal problems. The gastrointestinal system digests food, absorbs and transports vitamins and nutrients, detoxifies chemicals, and excretes the remainder. Gastrointestinal abnormalities can occur as a result of increased intestinal permeability and intestinal dysbiosis (an overgrowth/imbalance of intestinal flora), both of which can be caused by chronic inflammation/enterocolitis and/or the inability to properly break down proteins from foods (in particular gluten and casein). These can then permeate into the bloodstream, affecting other tissues and systems of the body, including the brain. The gastrointestinal and immune systems are closely related. If gastrointestinal issues are present, foods and nutrients won’t be processed or absorbed properly, so malnutrition, allergies, bacteria, yeast, antibodies, and further intestinal distress and pathology can develop. A significant portion of the immune system is located in the gastrointestinal tract, and chemical messengers in the gastroimmune system communicate with the rest of the body, including the brain. If gastrointestinal tissue damage, inflammation, and dysfunction are present, then distress will not only manifest in gastrointestinal symptoms such as abnormal stools, but dysfunction will manifest in other bodily systems such as the central nervous system. Clinical symptoms that can reflect gastrointestinal issues may include diarrhea, constipation, reflux, food cravings, bloating, fatigue, aggression, sleep issues, lethargy, “spaciness,” agitation, inappropriate laughing, self-stimulatory behavior, and selfinjurious behavior. As a practical example, if a child with undiagnosed gastrointestinal pathology is posturing (e.g., positioning their belly over the edge of furniture to exert pressure on their abdomen) or exhibiting selfinjurious behavior (e.g., biting their hand) at school when they are suffering from constipation, their focus upon relieving their gastrointestinal distress will also cause a lack of attention to schoolwork. Another child could exhibit aggressive behavior when gastroesophageal reflux is causing indescribable pain and the child is unable
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to communicate this to anyone. Particularly in the case of a nonverbal child, there may be no other means to communicate the physical distress except via behavior. Often school psychologists look for an antecedent, behavior, and consequence without considering underlying physiological issues that could potentially manifest as problematic behaviors. Often, children with autism are reinforced during their discrete trial lessons with treats that cause allergic reactions. This reaction can exacerbate negative behaviors. This not only causes additional distress to the child, but it results in problematic behaviors that are counterproductive to academic success during the remainder of the school day. This situation places stress upon both the child and the educators working with that child. According to the AAP in 2001, the first steps in investigating and remediating gastrointestinal issues in a given child can include nutritional supplementation, elimination diets, food allergy testing, and secretin. Detoxification and metabolic pathways The liver, the body’s primary means for detoxification, is designed to remove toxic matter from the bloodstream. Chronic gastrointestinal inflammation can adversely affect nutritional absorption which can affect detoxification. Methylation, the transfer of a methyl group, and sulfation, the biotransformation of a sulfur group, two metabolic pathways of the liver, are primarily responsible for a healthy body’s way of ridding itself of toxic substances. The methyl and sulfur groups do this by binding or conjugating themselves to the toxins thus facilitating the removal of the toxins from the body. Methylation is also a process by which methyl groups, pivotal components of the body’s biochemistry, are made available for numerous important chemical reactions throughout the body, such as DNA and RNA synthesis, and utilization of important nutrients such as folic acid, vitamin B6, and vitamin B12. If detoxification systems are overloaded or compromised, toxins can build up and cause oxidative stress, which can further impede proper cell function. Oxidative stress can also result in decreased production of glutathione, the body’s major antioxidant that protects cells from damage. If important detoxification pathways are
disrupted, multiple systems of the body can be adversely affected. In particular, the detoxification pathways that involve methylation and sulfation in the liver can become overburdened and fail to sufficiently remove the body’s toxin load. When this happens toxins accumulate in the body, which results in chemical sensitivities and cellular dysfunction. The combination of the malabsorption of essential nutrients due to gastrointestinal pathology combined with impaired detoxification mechanisms can overwhelm an individual’s ability to detoxify normally. Children with ASD often require nutritional supplements to bypass their nutritional insufficiencies and detoxification inadequacies. Two studies by James, et al. (2004, 2005), found low glutathione levels in children with autism due to abnormalities in their methionine pathway, which likely contribute to detoxification abnormalities. Studies by James, et al. (2004) also demonstrate that oxidative stress, and subsequent damage caused by build-up of metabolic byproducts due to glutathione depletion, may contribute to the development and associated clinical symptoms observed in autism. Recent studies have provided evidence that metabolic profiles of children with ASD present with a different methylation profile in comparison to control children. Significantly lower serum methionine, S-adnenosylmethionine (SAM), and homocysteine levels were found in children with ASD, pointing to reduced activity of methionine synthase and the decreased turnover of the methionine cycle (James, et al., 2006). Elevated S-adenosylhomocysteine (SAH) and adenosine levels evident in ASD further indicate a reduced methylation capability. Impaired detoxification can result in some of the following: sensory and speech issues, sleep difficulties, self-stimulatory and selfinjurious behaviors, aggression, compulsive behaviors, night sweats, anxiety, dilated pupils, and pica (compulsive cravings of non-food items, such as dirt, clay, cornstarch, glue, sand, and soap). Again, in an academic setting, negative behaviors such as inattentiveness and aggression could be a reflection of detoxification issues. It is important to be aware that in a
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school environment that includes children with sensitivity issues due to impaired detoxification pathways, negative behaviors can be exacerbated by exposure to commonly used building and cleaning materials; these materials include chemicals that outgas from new carpeting, paint, ammonia, tile glues, chlorine in swimming pools, and arsenic in treated wood in playground fences, decks, chips, and equipment. First steps in investigating and remediating detoxification issues in ASD children include addressing nutritional deficiencies and malabsorption issues, nutritional supplementation, and chelation therapy (AAP, 2001). Immune System The immune system defends the body against substances that appear foreign and harmful, including bacteria and viruses. Proper immune responses protect and defend against pathogens, remember how to respond, get more efficient over time, respond appropriately, and do no harm. When the immune response is compromised or reacts incorrectly, immune dysregulation, an abnormal balance and communication between immune cells, results. When this happens, the immune system cannot respond appropriately; as a result, the body might develop abnormal responses to things it might not normally react to, like foods. Frequent infections may also occur. A large part of the immune system is located in or near the intestinal tract to prevent
both microorganisms in the intestine and large food proteins from entering the rest of the body; therefore, defects in the immune system can lead to gastrointestinal problems and vice versa. Additional aberrant immune responses include chronic inflammation, allergies, and autoimmune reactions (when immune cells injure normal body tissues). These can occur individually or in combination. It is important to remember the immune system is closely connected to virtually every other system of the body. Over the past 30 years, findings related to differences in the systemic immune system in patients with autism have led to the theory that, in some cases, autism may be an immune-mediated or autoimmune disorder (Ashwood & Van de Water, 2004). Immune system issues can be expressed in any of the following ways: fevers, compulsive behaviors, self-injurious behaviors, skin rashes or eczema, impulsivity, aggression, and bowel problems including diarrhea, constipation, and enterocolitis. This is relevant to an academic situation because chronic inflammation, such as sinusitis or gastrointestinal swelling, can affect attentiveness, and the discomfort associated with these conditions can adversely affect behavior. First steps in investigating and remediating immune issues in ASD children rely upon restoring immunological balance and addressing food allergies, infections, and possible autoimmune disease.
Nervous system The nervous system is a network of specialized cells, including the brain, spinal cord, and numerous types of nerve cells, that process information and enable communication between parts of the body via neurotransmission. Any changes in the cells of the nervous system, like neuroinflammatory responses or developmental changes in neurocircuitry, can affect neurotransmission, cell function, and consequently affect behavior. Scientists at Johns Hopkins found that neurpathological changes in the brain tissues of autistic individuals were associated with inflammatory responses, neuroinflammation, and elevated inflammatory cell messengers, and could possibly relate to ongoing and chronic issues associated with central nervous system dysfunction observed in patients with autism (Pardo, et al., 2005; Vargas ,et al., 2005). Nervous system issues can result in dysfunction to any of the following: central auditory processing, expressive language, cognition, mood, sleep, motor planning, balance, hypo- or hyperactivity, and appetite. This is relevant in a learning environment because issues related to one or more of the previously listed nervous system functions can affect attention, focus, and behavior. Putting it all together: the best practices model approach Please see Figure 1 below. Overall, when dealing with a child with autism, issues
Figure 1
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associated with any of the systems of the body—in particular the digestive, immune, and nervous systems, and metabolic pathways—can lead to changes in behavior. Behavior is the key word. Autism is diagnosed on the basis of a constellation of abnormal behaviors. Children with autism often experience 18-24 months or more of abnormal developmental behaviors before they are diagnosed, and this delay results in a huge developmental gap prior to diagnosis and intervention. Once this early developmental period has been missed, it is extremely difficult to recapture. Therefore, early detection and behavioral intervention are important. Physical and/or occupational therapies as well as those targeting sensory issues may also be needed. However, underlying medical conditions can affect the child’s general well-being and responsiveness to behavioral therapies, and untreated comorbid biomedical conditions can slow down any progress. If the underlying medical conditions are treated, the result is increased receptiveness to behavioral and other related interventions. Not surprisingly, the synergistic effects of behavioral and biomedical interventions result in an increase in successful outcomes. Symptoms and behavioral effects n f a child suffers from allergies, focus I and concentration can be affected. n f a child suffers from gastrointestinal I distress, such as constipation or diarrhea, cramping and bloating will distract them; associated pain may lead to self-injurious behavior. n f the immune system isn’t functioning I properly, increasing infections, inflammation can affect attention and concentration. n f biochemical or metabolic pathways I aren’t functioning properly, neurotransmission can be under- or overstimulated and affect behavior. n f a child suffers from poor digestion, I improperly broken down foods can affect behavior; nutrients essential for metabolic pathways and cognition may be missing. n f detoxification isn’t functioning I properly, toxin burden increases and oxidative stress occurs, potentially affecting attention.
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All behavioral strategies can be thwarted by unresolved medical conditions. When children cannot express themselves verbally with language, they often use behaviors to do so.
All behavioral strategies can be thwarted by unresolved medical conditions. When children cannot express themselves verbally with language, they often use behaviors to do so. Therefore, anyone working with a child with autism needs to be aware of possible outward behavioral signs and symptoms that could relate to underlying medical conditions. Figure 2 (see page following) depicts images of symptoms and associated abnormal behaviors that can be used as red flags or visual cues indicating possible issues involving a system of the body. n osturing (a,b) and bloated stomach P (c) can reflect gastrointestinal system or immune system issues. n czema (d) and rashes and red ears (e) E can reflect immune system issues. n ound sensitivity (f) can be due to S immune system or nervous system issues; and n leep issues: waking, excessive S sleeping or lack of sleep (g,h), hyperactivity, giddiness (h); toileting issues: posturing, irritability prior to bowel movement (i), irritability, tantruming, unexplained crying (j), and self-injurious behavior (k) can all be related and interrelated with nervous, immune, and gastrointestinal systems. These symptoms can affect one or more systems of the body, and their expression can vary from child to child. These signs can help provide important clues related to possible medical conditions. An individualized approach to treatment must be employed. Summary The potential relationship between autism, gastrointestinal disorders, and autoimmunity has been the subject of much discussion and controversy in recent years. Recent literature explains how these systems are affected, and shows, if treated, how healing can improve health and behavior. Perhaps a paradigm shift in how autism is diagnosed and treated is occurring; perhaps in the future, autism will not be diagnosed as psychological condition, but rather as a neuro-gastroimmunological disorder resulting from a genetic susceptibility and an environmental insult(s). Research is beginning to describe autism, not only as a psychiatric disorder, but as a complex metabolic disease which can be treated and at least partially corrected. Children with autism—like all children— deserve medical treatment when they are unwell. A happier, healthier child is going to be more responsive to any intervention. In a best practices model for the treatment of autism, all these interventions must work together to address all the core symptoms for that particular individual, thereby providing the best possibilities for optimal success.
Acknowledgements I’d like to thank Dr. Jane El-Dahr for her thoughtful review and editing, Shannon Ellis for graphics formatting and figure enhancing, and Teri Arranga for her constructive editorial comments.
Children with autism—like all children—deserve medical treatment when they are unwell. A happier, healthier child is going to be more responsive to any intervention.
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Figure 2
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References
Ashwood P., & Van de Water, J. (2004). Is autism an autoimmune disease? Autoimmunity Reviews. 3, 557–562. Committee on Children with Disabilities, American Academy of Pediatrics. (2001). The pediatrician’s role in the diagnosis and management of autistic spectrum disorder in children. Management of children with autism spectrum disorders Pediatrics 107(5): 1221-1226. http://aappolicy. aappublications.org/cgi/reprint/ pediatrics;107/5/1221.pdf Filipek P.A., Accardo P.J., Baranek G.T,, Cook Jr. E.H., Dawson G., Gordon B., Gravel J.S., Johnson C.P., Kallen R.J., Levy S.E., Minshew N.J., Prizant, B.M, Rapin I., Rogers S.J., Stone W.L., Teplin S., Tuchman R.F., & Volkmar F.R. (1999). The screening and diagnosis of autistic spectrum disorders. J Autism Dev Disord; 29(6), 439-484. Johnson C.P. & Myer S.M. (2007). Identification and evaluation of children with autism spectrum disorders. Pediatrics,120,1183. Lord C., Cook E.H., Leventhal B.L. & Amaral, D.G. (2000). Autism spectrum disorders. Neuron, 28, 355–363. Lord C., Shulman C. & DiLavore, P. (2004). Regression and word loss in autistic spectrum disorders. J Child Psychol Psychiatry, 45, 936–955. Lord C., & Volkmar F.(2000). Genetics of childhood disorders: XLII. Autism, part 1: Diagnosis and assessment in autistic spectrum disorders. J Am Acad Child Adolesc Psychiatry. 41, 1134-1136. Jensen, V. K. & Sinclair, L. V. (2002). Treatment of autism in young children: behavioral intervention and applied behavior analysis. Infant and Young Children, 14(4), 42-52. Jyonouchi H., Sun S., & Itokazu N. (2002). Innate immunity associated with inflammatory responses and cytokine production against common dietary proteins in patients with autism spectrum disorder. Neuropsychobiology 46(2): 76-84. Jyonouchi H., Geng L., Ruby A. & Zimmerman-Bier B. (2005). Dysregulated innate immune responses in young children with autism spectrum disorers: their relationship to gastrointestinal symptoms and dietary intervention. Neuropsychobiology, 51(2), 77-85. Jyonouchi H., Geng L., Ruby A., Reddy C., & Zimmerman-Bier B.(2005). Evaluation of an association between gastrointestinal symptoms and cytokine prouction against common dietary proteins in children with autism spectrum disorders. J Pediatr, 146(5):605-610. James S.J., Melnyk S.B., Jernigan S., Janak L., Cutler P. & Neubrander J.M. (2004) Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with Autism. Amer J Clin Nutr 80:1611-1617. James S.J. Slikker III, W., Melnyk S., New E., Pogribna M. &Jernigan S. (2005) Thimerosal neurotoxicity is associated with glutathione depletion: protection with glutathione precursors. Neurotoxicology, 26: 1-8. James S.J., Melnyk S., Jernigan S., Cleves M.A., Halsted C.H., Wong D.H., Cutler P., Bock K., Boris M., Bradstreet J.J., Baker S.M. &Gaylor, S.W. (2006). Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. Am J Med Genet B Neuropsychiatr Genet, 141B(8): 947-956. Horvath K., Papadimitriou J.C., Rabsztyn A., Drachenberg C. & Tildon J.T. (1999). Gastrointestinal abnormalities in children with autistic disorder, J. Pediatrics, 135(5): 559-563. Horvath K. & Perman P.A.(2002). Autistic disorder and gastrointestinal disease. Curr Opinion in Pediatrics, 14: 583. Ming M., Brimacombe M., Chaaban J., Barbie Zimmerman-Bier, B., & Wagner G.C.(2008). Autism spectrum disorders: Concurrent clinical disorders. J Child Neurol, 23(1): 6-13. Pardo C.A., Vargas D.L. & Zimmerman A.W. (2005). Immunity, neuroglia and neuroinflammation in autism. International Review of Psychiatry, 17(6): 485-495. Rapin I. (1997) Autism. N Engl J Med, 337:97-104. Rapin I. The autistic-spectrum disorders. (2002) N Engl J Med,347:302-303. Shinnar S., Rapin I., Arnold S., Tuchman R.F., Shulman L., Ballaban-Gil K., Maw M., Deuel R.K., & Volkmar F.R. (2001). Language regression in childhood. Pediatr Neurol 24:183-189. Sulzer-Azaroff B. & Mayer R. Behavior analysis for lasting change. (1991). Fort Worth, TX: Holt, Reinhart & Winston, Inc. Van Gent T., Heijnen C.J., &Treffers P.D. (1997) Autism and the immune system. J Child Psychol Psychiatry, 38:337-349. Vargas C.L., Nascimbene C., Krishnan C., Zimmerman A.W. & Pardo C.A (2005). Neuroglial activation and neuroinflammation in the brain of patients with autism. Annals of Neurology, 57(1): 67-81. Volkmar F., et al.(1999). Practice parameters for the assessment and treatment of children, adolescents, and adults with autism and other pervasive developmental disorders. American Academy of Child and Adolescent Psychiatry Working Group on Quality Issues. J Am Acad Child Adolesc Psychiatry,38:32S. Volkmar F.R., & Pauls D. Autism.(2003). The Lancet 362:1133-41. Wakefield A. J., Anthony A., Murch S.H., Thomson M., Montgomery S.M., Davies S., O’Leary J.J., Berelowitz M., & WalkerSmith J.A.(2000) Enterocolitis in children with developmental disorders. Am J Gastroenterol, 5(9): 2285-2295.
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BIOMEDICAL
A Best PrActices Model for treAting AutisM to iMProve oPtiMAl outcoMes:
By Lauren Underwood, PhD
Lauren Underwood, PhD, received her doctorate in biology from Tulane University. Following graduation, she was awarded an NIH Post-Doctoral Training Grant Fellowship in vision research. She is the parent of a child recovering from autism and a health educator/
biomedical consultant for families of autistic children. Dr. Underwood is a Senior Staff Scientist for SSAI, Inc. supporting NASA. She is a Center for Autism and Related Disorders (CARD) IRB board member and has appeared in many peer-reviewed journals.
Introduction Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by deficits in socialization and communication as well as by abnormal behaviors patterns (Rapin, 1997; Lord, et al., 2000; Volkmar and Pauls, 2003). While most children who develop autism show abnormalities related to one of these key areas during infancy, the indicators may not become obvious until sometime during the second year of life. Research indicates that approximately 30–50 percent of children with ASD have a period of normal development, followed by developmental regression, with a loss of acquired skills, including language. This occurs anywhere between 16 and 25 months (Lord, et al., 2004) with the loss of acquired language typically occurring between the ages 12 and 18 months (Shinnar, 2001). Currently, autism is defined as a psychiatric disorder, not as a medical condition, and it is often perceived as a genetically-based mental disorder. There is no medical test for autism; therefore, diagnosis is based on a combination of psychological testing, complete history, physical examination, neurologic examination, non-medical evaluations (e.g., Checklist for Autism in Toddlers, Autism Diagnostic Observation Schedule, Autism Diagnostic InterviewRevised), and direct assessment/ observations of the child’s social, language,
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and cognitive development (Johnson, 2007; Filipek, et al., 1999; Volkmar et al., 1999). During normal development, milestones (skills or age-specific tasks that most children acquire within a certain age range) are naturally attained without being taught. Neurotypically developing children learn social and communication skills from their environment and from the people around them. The developmental milestones include gross motor, fine motor, language, cognitive, and social skills. In particular, the first three years of a child’s life is a developmentally dynamic time. When the term “developmental delay” is used (commonly the first diagnosis given to a child on the autism spectrum during an early intervention assessment or by a developmental pediatrician since the diagnosis of autism is often not given until the age of 4 or 5) it refers to a delay in one or more of the expected developmental milestones. Generally, these delays are ongoing and result in an overall major delay in the whole developmental process. During the period when autism seems to emerge, many significant milestones are delayed or even missed, thereby affecting normal behavioral development. As a result, more and more abnormal behaviors begin to display. Individually, behavioral treatments like applied behavior analysis (ABA) as well as medically-related biomedical approaches
have helped provide effective treatment modalities for autism. However, to optimize outcomes, a best practices model that applies these interventions together provides the best possibility for successful outcomes. This approach incorporates behavioralbiomedical treatment as a complementary synergistic model. The role of behavioral interventions Due to missed developmental milestones, children with autism are less equipped to acquire skills from their environment. Thus, behavioral interventions play an integral role in treating these children by reducing negative behaviors and increasing normal behaviors. Research shows the sooner a delayed child gets behavioral intervention, the better their progress will be. Treatment approaches grounded in behavioral interventions like ABA are considered invaluable as therapeutic and educational interventions for these children. In general, this educational framework manipulates antecedents and consequences of behavior to teach new skills and eliminate maladaptive behaviors. In particular, ABA uses behavioral analytic methods to understand current maladaptive behaviors and to change unacceptable behaviors into adaptive, acceptable ones. ABA systematically breaks down a task, skill, or behavior and then teaches the steps in sequence so a child significantly improves
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social behaviors. (Sulzer-Azaroff and Mayer, 1991). The most common ABA intervention, discrete trial training, is what most people think of when referring to ABA. The discrete trial enables the learner to acquire complex skills and behaviors by mastering the subcomponents of the targeted skill. However, ABA is not just discrete trials, but a behavioral program of comprehensive interventions, involving multiple settings, situations, and day-to-day activities. ABA has been scientifically studied and demonstrated to be highly effective for reducing negative behaviors in autism and increasing socially acceptable behaviors (Jensen and Sinclair, 2002). Given the considerable successful outcomes of autism treatments based on behavioral interventions like ABA, it is easy to understand why ABA is a necessary treatment. Several decades of research have proven ABA’s effectiveness for many children with autism. Many have achieved the optimal outcome: everyday functioning that is indistinguishable from that of typically developing peers. As a result, treatment approaches grounded in ABA are now considered the instrumental therapeutic and educational interventions for children suffering from this disorder. In addition, there is also strong support for complementary therapies, such as speech, occupational, physical, and sensory integration. Why biomedical interventions are necessary Although the etiology of ASD remains under investigation, research suggests that there is a genetic predisposition, which can be multifactorial and/or variable in expression (Lord, 2000). Numerous genes have been implicated in the susceptibility of certain individuals to have this disorder. Research also shows that children with autism suffer from multiple medical conditions involving dysfunction in the central and peripheral nervous systems as well as in the gastrointestinal and immune systems (Van Gent, 1997). Recent study supports a biomedical etiology for autism. While researchers are still investigating exact biological or metabolic pathways, case studies based on practical applications of this research suggest that
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The underlying concept of the biomedical approach is that the behavioral symptoms which define autism may be—at least in part—related to the child’s medical conditions. When these illnesses are addressed, psychological symptoms will improve.
successful outcomes improve when comorbid conditions—such as digestive disorders, immune system dysregulation and/or neuroinflammation—are treated. Literature provides evidence that comorbid conditions occur in children with autism (Ming 2008). Comorbidity is the occurrence of two or more disorders in the same person at the same time. Interactions between the co-existing conditions can affect the course, prognosis, and treatment outcome of cases of autism spectrum disorder. If these conditions are not addressed, they can affect developmental outcomes in other educational and sensory-related interventions. Today, treatments that address comorbid medical conditions, often associated with the underlying physiological imbalances that contribute to ASD symptoms, are emerging. Consequently, many parents and practitioners use medically-based treatment options, including modified diet, supplementation, and detoxification protocols. These biomedical treatments look at the application of natural, biological, and physical sciences to medicine and can include any of the following: healthier diet, nutritional supplementation, immune system regulation, gastrointestinal regulation, and detoxification as medically indicated. The underlying concept of the biomedical approach is that the behavioral symptoms which define autism may be—at least in part—related to the child’s medical conditions. When these illnesses are addressed, psychological symptoms will improve. The best practices model suggests that, if indicated, biomedical interventions should be used to stabilize the child’s medical symptoms in addition to implementing behavioral therapy. As a result, the child can maximize his or her learning potential. Anecdotal cases now demonstrate successful outcomes with an acceleration of skill acquisition within therapy programs in which biomedical issues are also addressed and treated. The position of the American Academy of Pediatrics “The Pediatrician’s Role in the Diagnosis and Management of Autistic Spectrum Disorder in Children” published in 2001 by the American Academy of Pediatrics (AAP) discusses specific strategies, including early intervention, behavioral management, habilitative therapies (speech occupational, and physical therapy), and medical management (including nutritional supplements, elimination diet, IVIG, secretin, and chelation), auditory integration training, and facilitated communication. The paper states that “ ... pediatricians should approach alternative therapies openly and compassionately ... and being willing to support a trial of therapy in select situations, and in such situations, requiring clear treatment objectives and pre-testing and post-testing.” Given this AAP recommendation, it is the responsibility of health care providers to educate family members and to help children with ASD by treating these conditions. In particular, there are several specific systems of the body that are often affected, including the immune system, the gastrointestinal system, the nervous system, and associated metabolic pathways. In support of biomedical treatments Autism is a whole-body condition. The systems of the body were meant to work together in a harmonious and integrated fashion to maintain good health. But when there is pathology in one bodily system, it can cause problems to another system. Gastrointestinal system Horvath, Wakefield, and others (1999, 2000, 2002) have shown that gastrointestinal inflammation is common in autism, which may lead to increased intestinal permeability, potentially causing abnormal immunologic responses to food proteins or pathogens. Three studies by Jyonouchi, et al. (2002, 2005a, 2005b), found that children
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with autism had more hypersensitivity to food allergens than did neurotypical children. These allergens are likely to cause gastrointestinal problems. The gastrointestinal system digests food, absorbs and transports vitamins and nutrients, detoxifies chemicals, and excretes the remainder. Gastrointestinal abnormalities can occur as a result of increased intestinal permeability and intestinal dysbiosis (an overgrowth/imbalance of intestinal flora), both of which can be caused by chronic inflammation/enterocolitis and/or the inability to properly break down proteins from foods (in particular gluten and casein). These can then permeate into the bloodstream, affecting other tissues and systems of the body, including the brain. The gastrointestinal and immune systems are closely related. If gastrointestinal issues are present, foods and nutrients won’t be processed or absorbed properly, so malnutrition, allergies, bacteria, yeast, antibodies, and further intestinal distress and pathology can develop. A significant portion of the immune system is located in the gastrointestinal tract, and chemical messengers in the gastroimmune system communicate with the rest of the body, including the brain. If gastrointestinal tissue damage, inflammation, and dysfunction are present, then distress will not only manifest in gastrointestinal symptoms such as abnormal stools, but dysfunction will manifest in other bodily systems such as the central nervous system. Clinical symptoms that can reflect gastrointestinal issues may include diarrhea, constipation, reflux, food cravings, bloating, fatigue, aggression, sleep issues, lethargy, “spaciness,” agitation, inappropriate laughing, self-stimulatory behavior, and selfinjurious behavior. As a practical example, if a child with undiagnosed gastrointestinal pathology is posturing (e.g., positioning their belly over the edge of furniture to exert pressure on their abdomen) or exhibiting selfinjurious behavior (e.g., biting their hand) at school when they are suffering from constipation, their focus upon relieving their gastrointestinal distress will also cause a lack of attention to schoolwork. Another child could exhibit aggressive behavior when gastroesophageal reflux is causing indescribable pain and the child is unable
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to communicate this to anyone. Particularly in the case of a nonverbal child, there may be no other means to communicate the physical distress except via behavior. Often school psychologists look for an antecedent, behavior, and consequence without considering underlying physiological issues that could potentially manifest as problematic behaviors. Often, children with autism are reinforced during their discrete trial lessons with treats that cause allergic reactions. This reaction can exacerbate negative behaviors. This not only causes additional distress to the child, but it results in problematic behaviors that are counterproductive to academic success during the remainder of the school day. This situation places stress upon both the child and the educators working with that child. According to the AAP in 2001, the first steps in investigating and remediating gastrointestinal issues in a given child can include nutritional supplementation, elimination diets, food allergy testing, and secretin. Detoxification and metabolic pathways The liver, the body’s primary means for detoxification, is designed to remove toxic matter from the bloodstream. Chronic gastrointestinal inflammation can adversely affect nutritional absorption which can affect detoxification. Methylation, the transfer of a methyl group, and sulfation, the biotransformation of a sulfur group, two metabolic pathways of the liver, are primarily responsible for a healthy body’s way of ridding itself of toxic substances. The methyl and sulfur groups do this by binding or conjugating themselves to the toxins thus facilitating the removal of the toxins from the body. Methylation is also a process by which methyl groups, pivotal components of the body’s biochemistry, are made available for numerous important chemical reactions throughout the body, such as DNA and RNA synthesis, and utilization of important nutrients such as folic acid, vitamin B6, and vitamin B12. If detoxification systems are overloaded or compromised, toxins can build up and cause oxidative stress, which can further impede proper cell function. Oxidative stress can also result in decreased production of glutathione, the body’s major antioxidant that protects cells from damage. If important detoxification pathways are
disrupted, multiple systems of the body can be adversely affected. In particular, the detoxification pathways that involve methylation and sulfation in the liver can become overburdened and fail to sufficiently remove the body’s toxin load. When this happens toxins accumulate in the body, which results in chemical sensitivities and cellular dysfunction. The combination of the malabsorption of essential nutrients due to gastrointestinal pathology combined with impaired detoxification mechanisms can overwhelm an individual’s ability to detoxify normally. Children with ASD often require nutritional supplements to bypass their nutritional insufficiencies and detoxification inadequacies. Two studies by James, et al. (2004, 2005), found low glutathione levels in children with autism due to abnormalities in their methionine pathway, which likely contribute to detoxification abnormalities. Studies by James, et al. (2004) also demonstrate that oxidative stress, and subsequent damage caused by build-up of metabolic byproducts due to glutathione depletion, may contribute to the development and associated clinical symptoms observed in autism. Recent studies have provided evidence that metabolic profiles of children with ASD present with a different methylation profile in comparison to control children. Significantly lower serum methionine, S-adnenosylmethionine (SAM), and homocysteine levels were found in children with ASD, pointing to reduced activity of methionine synthase and the decreased turnover of the methionine cycle (James, et al., 2006). Elevated S-adenosylhomocysteine (SAH) and adenosine levels evident in ASD further indicate a reduced methylation capability. Impaired detoxification can result in some of the following: sensory and speech issues, sleep difficulties, self-stimulatory and selfinjurious behaviors, aggression, compulsive behaviors, night sweats, anxiety, dilated pupils, and pica (compulsive cravings of non-food items, such as dirt, clay, cornstarch, glue, sand, and soap). Again, in an academic setting, negative behaviors such as inattentiveness and aggression could be a reflection of detoxification issues. It is important to be aware that in a
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school environment that includes children with sensitivity issues due to impaired detoxification pathways, negative behaviors can be exacerbated by exposure to commonly used building and cleaning materials; these materials include chemicals that outgas from new carpeting, paint, ammonia, tile glues, chlorine in swimming pools, and arsenic in treated wood in playground fences, decks, chips, and equipment. First steps in investigating and remediating detoxification issues in ASD children include addressing nutritional deficiencies and malabsorption issues, nutritional supplementation, and chelation therapy (AAP, 2001). Immune System The immune system defends the body against substances that appear foreign and harmful, including bacteria and viruses. Proper immune responses protect and defend against pathogens, remember how to respond, get more efficient over time, respond appropriately, and do no harm. When the immune response is compromised or reacts incorrectly, immune dysregulation, an abnormal balance and communication between immune cells, results. When this happens, the immune system cannot respond appropriately; as a result, the body might develop abnormal responses to things it might not normally react to, like foods. Frequent infections may also occur. A large part of the immune system is located in or near the intestinal tract to prevent
both microorganisms in the intestine and large food proteins from entering the rest of the body; therefore, defects in the immune system can lead to gastrointestinal problems and vice versa. Additional aberrant immune responses include chronic inflammation, allergies, and autoimmune reactions (when immune cells injure normal body tissues). These can occur individually or in combination. It is important to remember the immune system is closely connected to virtually every other system of the body. Over the past 30 years, findings related to differences in the systemic immune system in patients with autism have led to the theory that, in some cases, autism may be an immune-mediated or autoimmune disorder (Ashwood & Van de Water, 2004). Immune system issues can be expressed in any of the following ways: fevers, compulsive behaviors, self-injurious behaviors, skin rashes or eczema, impulsivity, aggression, and bowel problems including diarrhea, constipation, and enterocolitis. This is relevant to an academic situation because chronic inflammation, such as sinusitis or gastrointestinal swelling, can affect attentiveness, and the discomfort associated with these conditions can adversely affect behavior. First steps in investigating and remediating immune issues in ASD children rely upon restoring immunological balance and addressing food allergies, infections, and possible autoimmune disease.
Nervous system The nervous system is a network of specialized cells, including the brain, spinal cord, and numerous types of nerve cells, that process information and enable communication between parts of the body via neurotransmission. Any changes in the cells of the nervous system, like neuroinflammatory responses or developmental changes in neurocircuitry, can affect neurotransmission, cell function, and consequently affect behavior. Scientists at Johns Hopkins found that neurpathological changes in the brain tissues of autistic individuals were associated with inflammatory responses, neuroinflammation, and elevated inflammatory cell messengers, and could possibly relate to ongoing and chronic issues associated with central nervous system dysfunction observed in patients with autism (Pardo, et al., 2005; Vargas ,et al., 2005). Nervous system issues can result in dysfunction to any of the following: central auditory processing, expressive language, cognition, mood, sleep, motor planning, balance, hypo- or hyperactivity, and appetite. This is relevant in a learning environment because issues related to one or more of the previously listed nervous system functions can affect attention, focus, and behavior. Putting it all together: the best practices model approach Please see Figure 1 below. Overall, when dealing with a child with autism, issues
Figure 1
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associated with any of the systems of the body—in particular the digestive, immune, and nervous systems, and metabolic pathways—can lead to changes in behavior. Behavior is the key word. Autism is diagnosed on the basis of a constellation of abnormal behaviors. Children with autism often experience 18-24 months or more of abnormal developmental behaviors before they are diagnosed, and this delay results in a huge developmental gap prior to diagnosis and intervention. Once this early developmental period has been missed, it is extremely difficult to recapture. Therefore, early detection and behavioral intervention are important. Physical and/or occupational therapies as well as those targeting sensory issues may also be needed. However, underlying medical conditions can affect the child’s general well-being and responsiveness to behavioral therapies, and untreated comorbid biomedical conditions can slow down any progress. If the underlying medical conditions are treated, the result is increased receptiveness to behavioral and other related interventions. Not surprisingly, the synergistic effects of behavioral and biomedical interventions result in an increase in successful outcomes. Symptoms and behavioral effects n f a child suffers from allergies, focus I and concentration can be affected. n f a child suffers from gastrointestinal I distress, such as constipation or diarrhea, cramping and bloating will distract them; associated pain may lead to self-injurious behavior. n f the immune system isn’t functioning I properly, increasing infections, inflammation can affect attention and concentration. n f biochemical or metabolic pathways I aren’t functioning properly, neurotransmission can be under- or overstimulated and affect behavior. n f a child suffers from poor digestion, I improperly broken down foods can affect behavior; nutrients essential for metabolic pathways and cognition may be missing. n f detoxification isn’t functioning I properly, toxin burden increases and oxidative stress occurs, potentially affecting attention.
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All behavioral strategies can be thwarted by unresolved medical conditions. When children cannot express themselves verbally with language, they often use behaviors to do so.
All behavioral strategies can be thwarted by unresolved medical conditions. When children cannot express themselves verbally with language, they often use behaviors to do so. Therefore, anyone working with a child with autism needs to be aware of possible outward behavioral signs and symptoms that could relate to underlying medical conditions. Figure 2 (see page following) depicts images of symptoms and associated abnormal behaviors that can be used as red flags or visual cues indicating possible issues involving a system of the body. n osturing (a,b) and bloated stomach P (c) can reflect gastrointestinal system or immune system issues. n czema (d) and rashes and red ears (e) E can reflect immune system issues. n ound sensitivity (f) can be due to S immune system or nervous system issues; and n leep issues: waking, excessive S sleeping or lack of sleep (g,h), hyperactivity, giddiness (h); toileting issues: posturing, irritability prior to bowel movement (i), irritability, tantruming, unexplained crying (j), and self-injurious behavior (k) can all be related and interrelated with nervous, immune, and gastrointestinal systems. These symptoms can affect one or more systems of the body, and their expression can vary from child to child. These signs can help provide important clues related to possible medical conditions. An individualized approach to treatment must be employed. Summary The potential relationship between autism, gastrointestinal disorders, and autoimmunity has been the subject of much discussion and controversy in recent years. Recent literature explains how these systems are affected, and shows, if treated, how healing can improve health and behavior. Perhaps a paradigm shift in how autism is diagnosed and treated is occurring; perhaps in the future, autism will not be diagnosed as psychological condition, but rather as a neuro-gastroimmunological disorder resulting from a genetic susceptibility and an environmental insult(s). Research is beginning to describe autism, not only as a psychiatric disorder, but as a complex metabolic disease which can be treated and at least partially corrected. Children with autism—like all children— deserve medical treatment when they are unwell. A happier, healthier child is going to be more responsive to any intervention. In a best practices model for the treatment of autism, all these interventions must work together to address all the core symptoms for that particular individual, thereby providing the best possibilities for optimal success.
Acknowledgements I’d like to thank Dr. Jane El-Dahr for her thoughtful review and editing, Shannon Ellis for graphics formatting and figure enhancing, and Teri Arranga for her constructive editorial comments.
Children with autism—like all children—deserve medical treatment when they are unwell. A happier, healthier child is going to be more responsive to any intervention.
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Figure 2
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References
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