For many years, children with autism were thought to have emotional problems or to suffer from schizophrenia. However, it is now understood that autism spectrum disorder is a neurodevelopmental disorder, characterized by specific symptoms that vary in type and severity with each individual. In the last few years, the diagnosis of autism has changed dramatically, and many patients, parents, and healthcare professionals are facing an adjustment to these changes. The purpose of this course is to provide healthcare professionals with a basic understanding of a very complex condition, enabling them to provide more thorough patient care, recognize symptomatology, and educate patients, families, teachers and communities about autism spectrum disorder.
This course is designed for healthcare professionals in all practice settings who may be involved in the care of patients with an autism spectrum disorder.
NetCE is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. NetCE has been approved by NBCC as an Approved Continuing Education Provider, ACEP No. 6361. Programs that do not qualify for NBCC credit are clearly identified. NetCE is solely responsible for all aspects of the programs. NetCE, #1092, is approved as a provider for social work continuing education by the Association of Social Work Boards (ASWB) www.aswb.org through the Approved Continuing Education (ACE) Program. NetCE maintains responsibility for the program. ASWB Approval Period: 03/13/2016 to 03/13/2019. Social workers should contact their regulatory board to determine course approval for continuing education credits. NetCE is accredited by the International Association for Continuing Education and Training (IACET). NetCE complies with the ANSI/IACET Standard, which is recognized internationally as a standard of excellence in instructional practices. As a result of this accreditation, NetCE is authorized to issue the IACET CEU.
NetCE designates this continuing education activity for 5 ANCC contact hour(s). NetCE designates this continuing education activity for 6 hours for Alabama nurses. NetCE designates this continuing education activity for 3 NBCC clock hour(s). Social workers participating in this intermediate to advanced course will receive 5 Clinical continuing education clock hours, in accordance with the Association of Social Work Boards. NetCE is authorized by IACET to offer 0.5 CEU(s) for this program. AACN Synergy CERP Category A.
In addition to states that accept ANCC, NetCE is approved as a provider of continuing education in nursing by: Alabama, Provider #ABNP0353, (valid through December 12, 2017); California, BRN Provider #CEP9784; California, LVN Provider #V10662; California, PT Provider #V10842; Florida, Provider #50-2405; Iowa, Provider #295; Kentucky, Provider #7-0054 through 12/31/2017.
In addition to states that accept ASWB, NetCE is approved as a provider of continuing education by the following state boards: Alabama State Board of Social Work Examiners, Provider #0515; Florida Board of Clinical Social Work, Marriage and Family Therapy and Mental Health Counseling, CE Broker Provider #50-2405; Illinois Division of Professional Regulation for Social Workers, License #159.001094; Illinois Division of Professional Regulation for Licensed Professional and Clinical Counselors, License #197.000185; Illinois Division of Professional Regulation for Marriage and Family Therapists, License #168.000190; Texas State Board of Social Worker Examiners, Approval #3011; Texas State Board of Examiners of Professional Counselors, Approval #1121; Texas State Board of Examiners of Marriage and Family Therapists, Approval #425.
The purpose of this course is to provide healthcare professionals with a basic understanding of the very complex, misunderstood, often puzzling, and sometimes disabling condition, enabling them to provide more thorough patient care, recognize symptomatology, and educate patients, families, teachers, and communities about autism spectrum disorder.
Upon completion of this course, you should be able to:
- Define ASD, including the different types and incidence.
- Discuss theories related to the pathophysiology of ASD.
- Explain clinical features and diagnostic criteria of different types of ASD.
- List examples of ASD comorbidity.
- Discuss related medication management issues, including possible side effects/drug interactions.
- Discuss behavior modification, management issues, and techniques for parents to implement.
- Discuss education techniques and strategies for teachers and caregivers to implement.
Sharon M. Griffin, RN, PhD, specializes in Health Education and Chronic Disease Management especially as it relates to her primary areas of study and research. She has more than 30 years of healthcare experience nationwide and is an accomplished author, presenter and consultant. She frequently lectures on the subjects of Attention Deficit/Hyperactivity Disorder (AD/HD), Obsessive-Compulsive Disorder (OCD) and related disorders. Dr. Griffin is the cofounder of the University Center for Assessment and Learning (UCAL) of Andrews University in Berrien Springs, Michigan. She enjoys writing and teaching and has been listed in Who’s Who in American Nursing, Two Thousand Notable American Women, and the eleventh edition of the World Who’s Who of Women, Cambridge, England.
Contributing faculty, Sharon M. Griffin, RN, PhD, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.
Jane C. Norman, RN, MSN, CNE, PhD
Alice Yick Flanagan, PhD, MSW
The division planners have disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.
The purpose of NetCE is to provide challenging curricula to assist healthcare professionals to raise their levels of expertise while fulfilling their continuing education requirements, thereby improving the quality of healthcare.
Our contributing faculty members have taken care to ensure that the information and recommendations are accurate and compatible with the standards generally accepted at the time of publication. The publisher disclaims any liability, loss or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents. Participants are cautioned about the potential risk of using limited knowledge when integrating new techniques into practice.
It is the policy of NetCE not to accept commercial support. Furthermore, commercial interests are prohibited from distributing or providing access to this activity to learners.
- OVERVIEW OF AUTISM SPECTRUM DISORDER
- CURRENT THEORIES OF ASD PATHOPHYSIOLOGY
- A LOOK AT THE BRAIN IN AUTISM
- DIAGNOSTIC CRITERIA AND FEATURES OF ASD
- DISORDERS WITH AUTISTIC-LIKE FEATURES
- MANAGEMENT OF AUTISM SPECTRUM DISORDER
- EDUCATION STRATEGIES
- PROGNOSIS OF INDIVIDUALS WITH ASD
- Works Cited
- Evidence-Based Practice Recommendations Citations
Supported browsers for Windows include Microsoft Internet Explorer 9.0 and up, Mozilla Firefox 3.0 and up, Opera 9.0 and up, and Google Chrome. Supported browsers for Macintosh include Safari, Mozilla Firefox 3.0 and up, Opera 9.0 and up, and Google Chrome. Other operating systems and browsers that include complete implementations of ECMAScript edition 3 and CSS 2.0 may work, but are not supported.
#92201: Autism Spectrum Disorder
For several decades after the first description of autism in 1911, children with autism were thought to have emotional problems or to suffer from a type of schizophrenia. In the 1940s, the Austrian scientist Hans Asperger identified a similar syndrome, with social or emotional impairment as the core feature, that he termed "autistic psychopathy." Asperger's observations did not become widely known until 1981, and the syndrome was not included in medical diagnostic manuals until 1994 [66,74].
It is now understood that autism is a neurodevelopmental spectrum disorder, characterized by specific and similar behavioral symptoms that vary in type and severity with each individual . Although the independent diagnoses of autistic disorder, atypical autism, Asperger's disorder, childhood autism, childhood disintegrative disorder, early infantile autism, high functioning autism, Kanner's autism, and pervasive developmental disorder not otherwise specified (PDD-NOS) have been in common use for some time, these subtypes have largely been abandoned in favor of a diagnosis that reflects the current understanding of autism. Individuals with one of these previously established diagnoses, and any new cases, will now generally be given a diagnosis of autism spectrum disorder (ASD) .
Again, ASD is a neurodevelopmental disorder with a range of similar features that manifest differently in each patient . Although one individual may have severe symptoms and while another's are mild, both will fall under the category of ASD. In order to determine a diagnosis of ASD, professionals depend on observation of the behavioral characteristics of each patient; no medical tests are used in the diagnosis of ASD, although certain tests may be helpful in differentiating the condition from others with similar presentation.
The consolidation of the various "pervasive developmental disorder" subtypes (e.g., autistic disorder, Asperger's syndrome, PDD-NOS) into the single diagnosis of ASD reflects the current understanding of autism as a spectrum disorder. There has always been an overlap of behaviors and symptoms associated with each of the subtypes, and it has been shown that the clinic or institution where the patient was evaluated could influence the particular diagnosis more strongly than the severity or pattern of symptoms and behaviors . There has been much debate about whether new diagnostic criteria and re-diagnosis of patients using new criteria will create gaps in treatment or problems with insurance coverage, but the unreliability of the older criteria has necessitated a change. Studies have shown that most patients (91%) with a previously diagnosed pervasive development disorder are subsequently diagnosed with ASD .
One significant and controversial change in the field of autism medicine has been the American Psychiatric Association's (APA) latest revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM). The fifth edition of the manual (DSM-5), released in 2013, contains extensive changes to the diagnostic criteria for autism, including the unified diagnosis ASD and the coinciding consolidation of diagnostic criteria. According to the APA, the goal of the spectrum diagnosis and the ASD diagnostic criteria is "to make the diagnosis of autism spectrum disorder less subjective and more specific, correctly excluding those who do not have the diagnosis, while correctly identifying and including those who do" . Some patients who are found not to have ASD (e.g., because they only show deficits in social communication/interaction) may be given the new DSM-5 diagnosis social communication disorder.
In the DSM-5, there are seven behavioral impairments indicative of autism, of which five must be present to make a diagnosis of ASD (including all three social/communicative impairments) [79,88]. This is in contrast with the DSM-IV-TR, which included 12 criteria and no minimum criteria for a diagnosis of PDD-NOS [79,88]. The DSM-5 contains only two core deficits (versus three in the older version). Research has indicated that social and communication impairment stem from the same essential deficit, and their separation in the DSM-IV-TR was redundant .
The DSM-5 also separates primary (i.e., idiopathic) autism from secondary autism (i.e., caused by other medical conditions [e.g., Fragile X syndrome, Williams syndrome, epileptic spasms]). There are new provisions for naming the etiologic specifiers of ASD (e.g., ASD associated with a known medical or genetic condition or environmental factor). The major changes to the DSM will be discussed in detail throughout this course.
Please note that the term "parent" will often be used throughout this text to mean the legal guardian(s) or caregiver(s) of a child/adult with autism. A caregiver may be someone other than a biological or adoptive parent, including grandparents, foster parents, aunts, uncles, cousins, friends, or neighbors. All involved in the life of an autistic individual will benefit from this information. Also note that the terms "autism" and "ASD" are used interchangeably in this course. Although in the past autism has referred, more or less, to autistic disorder (i.e., "classical autism") the term is now generally used as shorthand for ASD .
Autism is the most common neurodevelopmental disorder in the United States. It exists in approximately 1 in 68 children at 8 years of age and is almost five times more common in boys than girls . Autism has no apparent prejudices and has been found worldwide in families of all racial, ethnic, and social backgrounds [3,5]. The occurrence of autism does not appear to be a result of family income, lifestyle, educational levels, or any known factors in the individual's psychological environment. More than 3.5 million people in the United States had some degree of autism in 2014 . It is the second most common developmental disability, more common than Down syndrome, yet most of us remain unaware of its impact and how to work effectively with autistic individuals .
Autism typically appears during the first three years of life. It can be a severely incapacitating, life-long developmental disability [3,7]. Autism is the result of a neurological disorder that affects functioning of the brain. It is a confusing disorder because it presents itself in unique ways in each affected individual, necessitating the use of the term "spectrum," which allows for individual differences among a group of people who share a common diagnosis. For instance, some children with autism may show severe cognitive impairment, whereas others may show incredible skills in math, memory, or art, but are severely lacking in social skills. Some individuals cannot speak, whereas others are verbal, though their speech may lack meaning to those around them. Some will insist on sameness in their environment, or detachment from it, and may also exhibit repetitive behavior and highly routine, unimaginative play [2,3].
Although the degrees of severity vary greatly from individual to individual, as is the case in many spectrum disorders, one common thread among those with autism is the impairment of communication skills in a social context. Lack of eye contact, rigid or concrete thinking, difficulty in processing information, sensory problems, anxiety, and echolalic speech are just a few of the factors that may interfere with an autistic individual's ability to create reciprocal social interactions [2,3].
Autism interferes with normal brain development in the regions that affect social interaction and communication skills. This makes communication arduous. Difficulties with verbal and nonverbal communication, social interactions, and leisure or play activities are common in individuals with autism. Repetitive body movements, such as hand flapping, unusual responses to others, atypical attachments to objects, and/or resistance to a change in their routines are often seen in individuals with autism.
Disturbances in the rate of development of physical, social, and language skills
Abnormal responses to sensations in any one or a combination of senses/responses (i.e., sight, hearing, touch, balance, smell, taste, reaction to pain, and/or the way a child holds his or her body)
Absent or delayed speech and language, while specific thinking capabilities may be present
Abnormal ways of relating to people, objects, and events
Autism occurs more frequently in some families than in others. The prevalence of autism among siblings of autistic individuals has been found to be substantially higher than in the general population (approximately 2% to 18%) . A higher prevalence has also been found in identical twins compared to nonidentical twins. Additionally, in some families with autistic children, researchers have identified parents who may have undiagnosed ASD. These findings seem to point to a common genetic base for autism [3,8].
As stated, the symptoms of autism may present along a spectrum on which one child appears to be different almost from birth and another shows a period of normal development before beginning to regress . The onset of autism typically occurs within the child's first year of life. Onset is delayed until the second or third year only about one-third of the time; however, this apparent delay may simply be a reflection of a parent's delayed detection or recognition of the symptoms of autism .
A delay in the early detection and recognition of the symptoms of autism may be compounded by the idiosyncratic nature of autistic children. For example, the autistic child who has an IQ near 70 and some functional language by 5 years of age appears to have a favorable developmental prognosis, whereas the autistic child who is nonverbal until well beyond 5 years of age may be diagnosed with an intellectual disability (e.g., mental retardation) only to later begin communicating and disprove the diagnosis. The wide variability in the intelligence among individuals with autism also compounds detection and recognition. For example, some children will require intense skill training and make slow or limited progress. Others will excel and move from treatment programs to challenging educational programs . One such individual is Temple Grandin, whose book, Emergence: Labeled Autistic, describes her own autistic life .
The diagnosis of ASD is made on the basis of two types of behaviors present and evident in the first few years of life :
Impaired social behavior/communication
Repetitive, restrictive (i.e., unimaginative) interests or activities
What, then, is the cause of this puzzling disorder? Although no clear-cut answer exists, researchers have some causal theories.
In the past, the dominant belief was that poor parenting caused autism. The term "refrigerator mother" or "refrigerator parent" has been used to describe emotionally frigid parents who were thought to be too distant, cold, and uncaring to allow the child to bond properly. During the 1960s, Bruno Bettelheim, a psychoanalyst, advocated the practice of removing autistic children from their parents as a means of treatment. This view has been referred to as the "psychogenic theory of autism;" however, it remains unsupported by the scientific and medical communities.
In contrast, the biological theory of autism continues to be supported by growing evidence. The biological theory maintains that autism involves one or more abnormalities in the brain that are caused by one or more biological factors (e.g., genes, complications during pregnancy or birth, or viral infections). Several clues have led researchers to conclude that some biological abnormality is at the root of autism.
Even though there are several medical conditions that may predispose a child to developing autism, in the majority of children, a medical condition cannot be found. To account for this puzzle, one theory that has been proposed is known as the final common pathway. In this model, various causes of autism (some of which have yet to be discovered) all share the characteristic of damage in the regions of the brain that are responsible for the development of normal communication, social functioning, and play .
It may be that one or more mental handicaps/disabilities/deficits are associated with autism because the damage from these various medical causes also disrupts those systems in the brain that are necessary for intellectual development. Precisely which part of the brain is responsible for autism is still unknown. Researchers are investigating and studying this aspect of the condition in many different centers around the world. Despite not yet having a definitive answer, the evidence that brain abnormalities exist in autism is no longer seriously doubted.
As previously mentioned, the biological theory of autism holds that various medical conditions (including gene mutations and/or environmental exposures in genetically predisposed individuals) may be the cause of ASD . If critical regions of the brain suffer abnormalities or damage from any of these conditions, the three main abnormal behaviors that characterize autism may occur.
The plausibility of the biological theory may be difficult to understand because, in many children, there may be no apparent medical condition, mental handicap/deficit, or epilepsy. However, studies of groups of children with ASD have found that certain medical conditions occur with greater frequency than in children without autism. The implication is that some biological cause is likely to lie behind all cases of autism, although it is only identifiable in a minority of cases.
When autism occurs in conjunction with a medical condition that is capable of damaging the nervous system, the medical condition is typically assigned as the cause of the autism. Medical conditions that are commonly identified with autism include [3,10,11,12]:
Fragile X syndrome
Tuberous sclerosis complex (TSC)
Other chromosomal anomalies
Cornelia de Lange syndrome
All of the medical conditions listed, though diverse, share the feature of being associated with brain damage or malfunction. However, it must be stressed again that not everyone with autism has had these medical conditions. Indeed, not everyone with these medical conditions develops autism. It is estimated that fewer than 10% of ASD cases are secondary .
In the early 1990s, the number of autistic diagnoses was steadily rising. Some believed this to be an epidemic, which pointed to a toxin or other environmental factor as the cause of autism. This perceived epidemic coincided with a change in the childhood vaccine schedule. Some parents of autistic children, along with certain grassroots organizations, turned their focus toward vaccines. They believed that a link existed between vaccines and autism because, at that time, certain vaccines contained the mercury-based preservative, thimerosal.
Thimerosal is 49.6% ethyl mercury, a known neurotoxin . It was used since the 1930s to keep vaccines from becoming contaminated with bacteria and fungi . By 1999, thimerosal was used in more than 30 U.S. vaccines. Although the amount of thimerosal used in each vaccine was less than the amount considered toxic by the Environmental Protection Agency (EPA), when the amounts from all of the required vaccinations for infants were added altogether, the sum exceeded the safe level .
A link between mercury and autism had been speculated even before that time. An early study by the Centers for Disease Control and Prevention (CDC) suggested a possible connection between the amount of thimerosal given and certain neurodevelopmental disorders, such as attention deficit hyperactivity disorder (ADHD), speech and language delays, and tics. However, further review led many to feel that this study was flawed . In addition, contrary to the perception of an autism epidemic, many experts believed that the rise in the number of autism diagnoses had been primarily due to changes in diagnostic criteria (i.e., from autism to ASD) and a heightened awareness about and recognition of autism [16,17].
In 1999, the American Academy of Pediatrics (AAP) and the U.S. Public Health Service recommended removing thimerosal from vaccines. However, this was mainly done as a precautionary measure to reduce the population's heavy metal exposure wherever possible. By 2001, all vaccines that were routinely recommended for children in the United States were available without thimerosal .
The Institute of Medicine (IOM) convened several committees to examine the existing evidence and determine if there was a causal relationship between autism and thimerosal [19,20]. The eighth and final report published in 2004 by the IOM Immunization Safety Review Committee concluded that the evidence favored rejection of a causal relationship between thimerosal-containing vaccines and autism .
A study of the prevalence of autism in California children, conducted from 1995 to 2007, found that autism rates had continued to increase after thimerosal was eliminated from most childhood vaccines. These results supported the IOM conclusion that thimerosal is not a primary cause of autism .
Although CDC supports the IOM conclusion, it continues to emphasize its ongoing commitment to protecting the health of children and infants in the United States and to understanding the causes of autism .
Research has indicated that approximately 2% to 18% of siblings of autistic individuals will also develop autism [3,24,25,26,78]. This is a much higher rate than chance alone would predict, which indicates that some cases of ASD may be hereditary. Alone, this finding does not give any clue to the cause of this family pattern. Proof that genetic factors are involved comes from studies of twins. To review, monozygotic, or identical twins, come from the same fertilized egg and are, therefore, genetically identical. In contrast, dizygotic, or nonidentical twins, develop from two separately fertilized eggs and are, therefore, in genetic terms, the same as any other sibling (i.e., they share only half of their sibling's genes). In studies of twins, researchers look at sets of identical and nonidentical twins in which at least one of the twins has a disability. In studies of this type for autism, researchers have found that the rate of both identical twins having autism is significantly higher than the rate in nonidentical twins. Studies have also indicated that identical twins have a concordance rate for ASD between 36% and 95%. The rate for nonidentical twins is 0% to 31% [3,27,28]. Although this is strong evidence that some genetic cause exists for autism, the chance of both identical twins developing ASD is not 100% and may be very low more than 12 months post-diagnosis .
Increasingly, genetic research is being completed to determine the cause of ASD. Studies have shown that at different levels of implication, 15 or more chromosomes may be involved in the development of ASD [22,30,31,32]. One example is the language and speech region, located on chromosome 7q31–7q33 within the autism susceptibility locus 1 (AUTS1), which is reputed to be strongly linked to autism. Linkages to autism in overlapping regions span chromosomes 7q21–7q34 [28,33]. In addition, most persons with a deletion or duplication of part of chromosome 16 (16p11.2 deletion syndrome) have signs of autism .
Other studies have assessed autism risk in families with more than one member affected by ASD. Researchers have found patterns that divide this autism risk into two categories: sporadic and inherited. Sporadic autism was associated with low-risk families, whose disorder causation was attributed to spontaneous mutation, mostly affecting males. Inherited autism was linked to offspring, mostly females, who carry a causative mutation. Most of these females were not affected by the genetic mutation but have the opportunity to pass it on to their offspring. This model is based on the genetic data of monozygotic and dizygotic twins and, therefore, only one aspect of possible genetic causation [34,35]. In fact, a number of rare, genetic conditions have been associated with autism [3,10,11,12,36,37,38,39]:
Phenylketonuria (PKU): PKU is an inherited condition involving a lack f the enzyme that allows the body to metabolize the naturally occurring chemical, phenylalanine. As a consequence, there is a build-up of related toxins in the body, which may damage the brain. PKU is treated by initiating a special diet for infants found to have the abnormal gene. Before the discovery of this treatment, PKU resulted in brain damage, and, on occasion, autism. Fortunately, autism due to PKU is now very rare.
Neurofibromatosis (von Recklinghausen's disease): This genetic condition primarily affects the growth of neural tissue. As a result, mental handicap/disability/deficit may occur due to brain damage.
Tuberous sclerosis complex: Some studies have indicated that autism is quite common in children who have the genetic condition tuberous sclerosis, co-occurring in 25% to 50% of cases. However, because tuberous sclerosis itself is so rare, it is still an uncommon cause of autism. The features of tuberous sclerosis may include unusual skin pigmentation and a particular facial rash. The most significant feature is the growth of tumors in the brain and/or other vital organs, although not all of these features need to be present. Tuberous sclerosis may also give rise to a special form of epilepsy known as epileptic spasms (formerly infantile spasms). This type of epilepsy has also been proposed as a cause of autism, so it is possible that the link between autism and tuberous sclerosis merely reflects the common association with epileptic spasms. However, more recent evidence questions whether this is the case and suggests that it may be some other characteristic of tuberous sclerosis (possibly abnormalities in brain development) that leads to the development of autism.
Fragile X syndrome: Children with Fragile X syndrome usually develop mental handicap/disability/deficit and often have an unusual facial appearance (i.e., large protruding ears, a long nose, and a high forehead). The syndrome is called Fragile X because people with this condition have an abnormal gap on their X chromosome. Fragile X occurs in a small proportion (approximately 15% to 25%) of children with autism. This percentage nevertheless makes it the most common cause of autism yet identified.
Other conditions: Moebius syndrome (a birth defect affecting the sixth and seventh cranial nerves, which control the eye and face muscles) and a number of other congenital anomaly syndromes (disorders characterized by particular constellations of defects that are present from birth) have also been associated with autism.
To summarize, a range of genetic conditions can cause autism; however, these do not account for all cases of autism.
Mother older than 35 years of age
Birth order (first, fourth, or later-born children may carry a slightly higher risk)
Medication during pregnancy
Meconium present in the amniotic fluid during labor
Bleeding between the fourth and eighth month of pregnancy
A rhesus incompatibility between the mother's and the child's blood groups
Low birth weight (less than 2500 g or 5.5 lbs)
The identification of these factors suggests that difficulties in pregnancy or delivery may cause brain damage in the infant. Although a number of birth and pregnancy complications have been associated with autism, alone they are probably not sufficient to cause the condition. It is more likely that they either operate in combination with other factors or are indications of existing abnormalities [4,43]. It is important to note, however, that these factors are evident in only a minority of children with autism.
One study has hypothesized a possible link between autism and elevated fetal testosterone levels in amniotic fluid. More research is necessary to determine if the elevated testosterone levels are causative or the result of an autistic condition .
In addition to genetic and birth or pregnancy factors, infections that damage the brain during fetal development or childhood have also been associated with autism. It is assumed, in these cases, that the infections are causal; however, as with birth complications, this need not be so. Although the evidence is not clear in this respect, infections that have been reported in association with autism include the following [3,45,46,47,48]:
Rubella: The rubella virus, particularly if contracted in the first 3 months of pregnancy, may damage the fetal brain and result in mental handicap/disability/deficit, deafness and blindness, as well as autism. With current vaccination programs against rubella, however, this is no longer a common problem. Additionally, epidemiological studies have found no association between vaccination for the rubella virus and autism.
Cytomegalovirus (CMV): The CMV may also result in mental handicap/disability/deficit and, more rarely, autism. However, many newborn children who have been exposed to CMV have no apparent problems. Thus, other factors must also operate to cause autism in these cases.
Herpes encephalitis: The herpes virus can sometimes infect an infant's brain. This may lead to a brain inflammation known as encephalitis. Occasionally, children who develop herpes encephalitis display an autistic-like condition.
The current assumption is that in all children with autism there is some, though possibly very subtle, brain damage. Where none can be physically found, it is assumed that this is because our diagnostic equipment is not yet sensitive enough. Because the child may appear physically normal, parents may wonder whether there really is any brain damage. However, the idea that brain damage is the cause of autism is still widely held because, in many cases, brain abnormalities are found.
Various techniques have been developed for obtaining pictures of the brain. These include: computed axial tomography (CAT or CT) scans, single photon emission tomography (SPECT), magnetic resonance imaging (MRI) scans, and positron emission tomography (PET) scans. All of these types of scanning methods have been used in autism research. For example, one study used an MRI to measure the head circumference in autistic children. A two-phase, abnormal growth trend was observed. The trend showed normal, or slightly smaller than normal, head circumference at birth, followed by a sudden growth, or overgrowth, at approximately 1 year of age [49,50]. Findings are wide-ranging, with abnormalities being found in many different parts of the brain. However, as with postmortem examinations, there is no clear evidence of a specific abnormality unique to autism.
Regarding electrical activity of the brain, there are a number of methods for studying the way the nervous system operates. Most of these methods involve measuring electrical signals emitted by the brain and its nerves while they are functioning. The best known means of measuring brain electrical activity involves the electroencephalogram (EEG). Using the EEG, researchers have been able to examine electrical activity in the brains of people with autism. Studies of systems-level brain abnormalities and disordered connectivity among the brain's networks are areas of ongoing interest and research. However, as with the postmortem and scanning investigations, these studies have revealed no clear-cut abnormality that is uniquely associated with autism [51,52,53].
The only brain chemical that has clearly been found in abnormal levels in autism is the neurotransmitter serotonin. It has been discovered that many individuals with autism have abnormally high levels of serotonin in the blood. This phenomenon is known as the platelet hyperserotonemia of autism . Exactly why the levels are high is not known. Variations in how some individuals metabolize serotonin are another potential factor in the pathophysiology of autism that is being investigated . In children who are developmentally disabled alone, serotonin may also be elevated. Interestingly, one study showed that low plasma serotonin levels in a pregnant woman may be a risk factor for autism in her child . Another study suggested that high levels of platelet serotonin may be used as a possible marker for familial autism; however, research results have produced conflicting results [57,58,59].
One theory of autism that has been proposed suggests that many of the psychological features of autism may be accounted for by postulating abnormalities in the frontal lobes of the brain. This is because many patients who acquire brain damage in the frontal lobe often show similar psychological deficits and traits. This theory is also being researched [60,61]. Other theories related to dysfunctions in the brain link the deficits to the amygdala temporal lobe, or cerebellum.
In a 2007 study, researchers confirmed previous anecdotal reports from parents and case reports from clinicians that showed improvement in ASD behavior when patients were febrile . Researchers believe that the causative mechanisms, rather than the fever itself, effected the change in behavior. The involvement between the immune system and nervous system during fevers are complex . More research is needed to better understand the role of fever and the neuropathways that are implicated.
The two core clinical features of autism include difficulties in receptive and expressive social communication/social interaction and the presence of restricted/repetitive patterns of behavior, interests, and activities . Delays in or absence of the development of spoken language is common in the child with autism. In some instances, language begins to develop appropriately and then seems to stop suddenly. The child with less severe autism may develop elaborate language, but have a hard time initiating and sustaining a conversation. Some children may mimic the communication of others, a condition known as echolalia .
Autism is a behavioral syndrome, meaning there is a cluster of abnormal types of behavior. The diagnosis of autism is only made if all other medical psychosocial causes are ruled out and if the cluster of core behaviors is present. To review, the core features of ASD are :
The child's social relationships and social development are abnormal, and the child is failing to develop normal communication.
The child's interests, activities, and behaviors are restricted and repetitive, rather than flexible and imaginative.
It is worth stressing that a diagnosis of autism is not made merely because a child has problems in communication, social interaction, or imagination, but only when these types of behavior all occur together, in varying degrees, signifying the distinctive pattern of autism. For example, difficulty sharing in imaginative play is a strong marker of autism; this type of play is normal for children, and involves both social communication skills and flexible, adaptive thinking. Naturally, in defining autism in this way, it is crucial to understand what is meant by normal development. This in itself is complex; therefore, the diagnosis can only really be made by experts who have considerable experience in recognizing both normal and abnormal child development.
As discussed, the diagnostic criteria for autism have changed considerably in the DSM-5. There are five criteria that must be met to make a diagnosis of ASD . The diagnosis is recorded with specifiers indicating accompanying impairments (e.g., intellectual, language); associated known medical, genetic, or environmental factors; associated neurodevelopmental, mental, or behavioral disorder(s); and the severity of the symptoms. The severity of each of the two core deficits (i.e., social/communication deficits and behavioral symptoms) are recorded separately, and assessment of verbal and nonverbal proficiency is also essential. These are necessary to make an accurate intellectual profile and to help with interpretation of the diagnostic features in each patient. The DSM-5 diagnostic criteria are :
A. Persistent deficits in social communication and social interaction across multiple contexts, as manifested by the following, currently or by history:
Deficits in social-emotional reciprocity, ranging, for example, from abnormal social approach and failure of normal back-and-forth conversation; to reduced sharing of interests, emotions, or affect; to failure to initiate or respond to social interactions
Deficits in nonverbal communicative behaviors used for social interaction, ranging, for example, from poorly integrated verbal and nonverbal communication; to abnormalities in eye contact and body language or deficits in understanding and use of gestures; to a total lack of facial expressions and nonverbal communication
Deficits in developing, maintaining, and understanding relationships, ranging, for example, from difficulties adjusting behavior to suit various social contexts; to difficulties in sharing imaginative play or in making friends; to absence of interest in peers
Specify current severity (Table 1).
SEVERITY LEVELS FOR AUTISM SPECTRUM DISORDER
|Severity Level||Social Communication||Restrictive, Repetitive Behaviors|
|Level 3 (requiring very substantial support)||Severe deficits in verbal and nonverbal social communication skills cause severe impairments in functioning, very limited initiation of social interactions, and minimal response to social overtures from others. For example, a person with few words of intelligible speech who rarely initiates interaction and, when he or she does, makes unusual approaches to meet needs only and responds to only very direct social approaches||Inflexibility of behavior, extreme difficulty coping with change, or other restricted/repetitive behaviors markedly interfere with functioning in all spheres. Great distress/difficulty changing focus or action.|
|Level 2 (requiring substantial support)||Marked deficits in verbal and nonverbal social communication skills; social impairments apparent even with supports in place; limited initiation of social interactions; and reduced or abnormal responses to social overtures from others. For example, a person who speaks simple sentences, whose interaction is limited to narrow special interests, and how has markedly odd nonverbal communication.||Inflexibility of behavior, difficulty coping with change, or other restricted/repetitive behaviors appear frequently enough to be obvious to the casual observer and interfere with functioning in a variety of contexts. Distress and/or difficulty changing focus or action.|
|Level 1 (requiring support)||Without supports in place, deficits in social communication cause noticeable impairments. Difficulty initiating social interactions, and clear examples of atypical or unsuccessful response to social overtures of others. May appear to have decreased interest in social interactions. For example, a person who is able to speak in full sentences and engages in communication but whose to-and-fro conversation with others fails, and whose attempts to make friends are odd and typically unsuccessful.||Inflexibility of behavior causes significant interference with functioning in one or more contexts. Difficulty switching between activities. Problems of organization and planning hamper independence.|
B. Restricted, repetitive patterns of behavior, interests, or activities, as manifested by at least two of the following, currently or by history:
Stereotyped or repetitive motor movements, use of objects, or speech (e.g., simple motor stereotypies, lining up toys or flipping objects, echolalia, idiosyncratic phrases)
Insistence on sameness, inflexible adherence to routines, or ritualized patterns of verbal or nonverbal behavior (e.g., extreme distress at small changes, difficulties with transitions, rigid thinking patterns, greeting rituals, need to take same route or eat food every day)
Highly restricted, fixated interests that are abnormal in intensity or focus (e.g., strong attachment to or preoccupation with unusual objects, excessively circumscribed or perseverative interest)
Hyper- or hyporeactivity to sensory input or unusual interests in sensory aspects of the environment (e.g., apparent indifference to pain/temperature, adverse response to specific sounds or textures, excessive smelling or touching of objects, visual fascination with lights or movement)
Specify current severity (Table 1).
C. Symptoms must be present in the early developmental period (but may not become fully manifest until social demands exceed limited capacities or may be masked by learned strategies in later life).
D. Symptoms cause clinically significant impairment in social, occupational, or other important areas of current functioning.
E. These disturbances are not better explained by intellectual disability (intellectual developmental disorder) or global developmental delay. Intellectual disability and autism spectrum disorder frequently co-occur; to make comorbid diagnoses of autism spectrum disorder and intellectual disability, social communication should be below that expected for general developmental level.
Individuals with a well-established DSM-IV diagnosis of autistic disorder, Asperger's disorder, or pervasive developmental disorder not otherwise specified should be given the diagnosis of ASD. Individuals who have marked deficits in social communication, but whose symptoms do not otherwise meet the criteria for ASD, should be evaluated for social (pragmatic) communication disorder . Potential specifications include with intellectual impairment; with language impairment; with catatonia; associated with a known medical or genetic condition or environmental factor; or associated with another neurodevelopmental, mental, or behavioral disorder.
Researchers now advocate early intervention for the successful management of ASD and advise against the traditional "wait-and-see" approach . The American Academy of Child and Adolescent Psychiatry recommends that the developmental assessment of young children (including infants) and the psychiatric assessment of all children should routinely include questions about ASD symptomology . Guidelines developed by the American Academy of Neurology (AAN) and the Child Neurology Society have also recommended that developmental surveillance be performed (using recommended screening tools) at all well-child visits, beginning at infancy and continuing through school-age, and that the evaluations be repeated any time concerns about the child's developmental progress are raised (i.e., not meeting developmental milestones) . Developmental screening tools recommended by the AAP and AAN include the Ages and Stages Questionnaire, the BRIGANCE Early Childhood Screens, the Child Development Inventories, and the Parents' Evaluations of Developmental Status [31,32].
After considering the parent's assessment and the clinical observations, the pediatrician should assess a positive or negative screening for developmental delays, as discussed, using one of the recommended screens. If specific behaviors are exhibited by the child (Table 2), immediate evaluation for autism should be performed using one if the validated screening instruments . If the screening is positive for ASD, a standard psychiatric assessment should be followed, including interviews with the child and family, review of past records, and a full history .
A medical assessment is also necessary and typically includes a physical examination, a hearing screen, and genetic testing . Psychological tests, communication assessment, and occupational/physical therapy evaluations are warranted.
BEHAVIORAL CUES INDICATING THE NEED FOR REFERRAL TO A SPECIALIST
|No babbling, pointing, or other gestures||By 12 months of age|
|No single words||By 16 months of age|
|No two-word, spontaneous (nonecholalic) phrases||By 24 months of age|
|Any lack of developmentally-appropriate language or social skills||At any age|
Autism can, at first glance, be confused with a number of conditions. It may, for example, appear similar to selective mutism, a condition in which the child simply refuses to talk in certain situations (e.g., when one is expected to speak at school) . It may also resemble reactive attachment disorder, a condition in which the child fails to develop stable emotional bonds with parents or caregivers. This may occur following abuse, deprivation, or family problems, and the child may exhibit delays in cognition and language . Autism is also superficially similar to language disorder, whereby language is delayed, but where social development may be relatively normal [64,65,88]. Various kinds of mental handicap, in which all skills, including social ones, are delayed, may also sometimes resemble autism.
One potential complication in the diagnosis of ASD is that autism-like symptoms may be present, but with one or more of the features missing. In the past, a child may have been diagnosed with Asperger's disorder or atypical autism when only one or two autistic features were present, and the features may not have necessarily appeared before 3 years of age. As discussed, the revised diagnostic criteria for ASD are an attempt to better identify individuals with autism and rule out autism in those who do not. The DSM-5 criteria for social communication disorder essentially contain only the social/communication criteria from the ASD category (Table 3). It is thought that the minority of individuals that do not meet the DSM-5 criteria for ASD upon rediagnosis due to a lack of repetitive and restrictive behaviors and interests may be diagnosed with social communication disorder .
SOCIAL (PRAGMATIC) COMMUNICATION DISORDER: DIAGNOSTIC CRITERIA
A. Persistent difficulties in the social use of verbal and nonverbal communication as manifested by all of the following:
B. The deficits result in functional limitations in effective communication, social participation, social relationships, academic achievement, or occupational performance, individually or in combination.
C. The onset of the symptoms is in the early developmental period (but deficits may not become fully manifest until social communication demands exceed limited capacities).
D. The symptoms are not attributable to another medical or neurological condition or to low abilities in the domains or word structure and grammar, and are not better explained by autism spectrum disorder, intellectual disability (intellectual developmental disorder), global developmental delay, or another mental disorder.
All alternative diagnoses should be firmly ruled out before a child is given the diagnosis of autism [4,88]. Other conditions, such as Rett syndrome and Landau-Kleffner syndrome, may also mimic the symptoms of autism, so careful assessment is essential [4,67,68].
Brain abnormalities that are thought to underlie autism may produce anomalies in psychological functioning. Again, the two key psychological problems in children with autism are in the development of social relationships/communication and an insistence on sameness/inability to adapt .
An inability to relate socially to other people is possibly the most readily apparent signal when diagnosing autism. Leo Kanner, who described autism in 1943, gave what is perhaps still the clearest account of the social difficulties in these children. The following extracts from the descriptions produced by Kanner and a colleague indicate that there is no single social abnormality in autism, but rather a range :
Unresponsiveness to people. "He seems almost to draw into his shell and live within himself."
Lack of attention to people. "When taken into a room, he completely disregarded the people and instantly went for objects."
Treating parts of people as detached objects. "When a hand was held out to him so that he could not possibly ignore it, he played with it briefly as if it were a detached object."
Lack of eye contact. "He did not respond to being called, and did not look at his mother when she spoke to him."
Treating people as if they were inanimate objects. "He never looked up at people's faces. When he had any dealings with persons at all, he treated them, or rather parts of them, as if they were objects. He would use a hand to lead him. He would, in playing, butt his head against his mother as at other times he did against a pillow. He allowed his mother's hand to dress him, paying not the slightest attention to her."
Lack of behavior appropriate to cultural norms. "At two years old, she was sent to a nursery school, where she independently went her way, not doing what the others did. She, for instance, drank the water and ate the plant when they were being taught to handle flowers."
Attention to the nonsocial aspects of people. "At the Child Study Home, she soon learned the names of all the children, knew the color of their eyes, the bed in which each slept, and many other details about them, but never entered into any relationship with them."
Lack of awareness of the feelings of others. ". . . on a crowded beach he would walk straight toward his goal irrespective of whether this involved walking over newspapers, hands, feet, or torsos, much to the discomfiture of their owners. His mother was careful to point out that he did not deviate from his course in order to walk on others, but neither did he make the slightest attempt to avoid them. It was as if he did not distinguish people from things, or at least did not concern himself about the distinction."
Lack of savoir-faire. "Even the relatively 'successful' children exhibited a lack of social perceptiveness. This can be best illustrated by the following incident involving one of our patients who had made considerable progress: Attending a football rally of his junior college and called upon to speak, he shocked the assembly by stating that the team was likely to lose, a prediction that was correct but unthinkable in the setting. The ensuing round of booing dismayed this young man, who was totally unable to comprehend why the truth should be unwelcome."
All of these descriptions highlight the lack of normal social interest and social understanding. They also make it clear that not all children with autism are in a world of their own. Some spontaneously approach other people, but may only carry out a repetitive, idiosyncratic preoccupation, such as touching another person's clothes or hair or asking a limited set of questions.
The classic picture of aloneness is seen most often in children with autism who are younger than 5 years of age. As they get older, these children tend to become more outgoing. One important point to take from Kanner's descriptions is that if people with autism become more outgoing socially, this does not necessarily mean that their social behavior has become normal .
It is often claimed that children with autism avoid eye contact with others. However, studies have suggested that children with autism simply look at everything for shorter periods of time, not less at the eyes of another in particular. This may give other people the impression that children with autism are avoiding eye contact, whereas in reality it may not be so deliberate. Nevertheless, there is something odd about their use of eye contact. They do not seem to understand how to use eye contact to communicate without words or to read other people's faces [69,70].
Many young children with autism do have relationships with their parents, in that they appear to be emotionally attached to their parents. Some children also show the social smile at the normal time (i.e., at six weeks of age) and continue to smile in an affectionate way. However, this does not mean that their relationships are normal. The emotions that children with autism show within relationships may also be quite unexpected. For example, most show the simple emotions of anger, fear, joy, and sadness, but may do so in situations when most people would not show these .
A large part of the social deficits seen in ASD stems from language difficulties. A range of communication difficulties exists on many levels. The following are several deficits to consider [4,71,72,73]:
Preverbal communication: Normal children use many different types of communicative behavior by the end of their first year. One set of behaviors is joint-attention behavior. These include pointing in order to request objects or to comment to another person about some object or event, and showing and giving objects to other people in order to communicate their interest in the object or their desire for it. Children with autism rarely display any pointing and showing. Often, they simply grab the object, ignoring the adult or other child who is holding it.
Nonverbal communication: Normal children and adults use gestures to accompany speech or to express emotions, embellishing with the appropriate eye contact and facial expressions. This nonverbal communication is also abnormal in autism, with facial expression often not matching intonation, or gesture being out of step with speech. Speech may also be abnormal.
Disordered expressive prosody: Researchers have reported that a majority of children with less severe ASD have an impaired ability to use language expressively (i.e., they do not use proper rhythm, stress, and intonation).
Abnormalities in speech: Many children with autism never develop any useful speech at all; that is, they never produce sounds that are recognizable as words. These children are therefore described as functionally mute. For such children, communication problems are paramount, and even attempts at using nonspeech systems, such as sign language, may be relatively limited in success. Unusual features may be seen in the autistic child who does develop speech. These include:
Echolalia: The child will echo words or phrases either immediately after hearing them or at a later time. Many normal children go through a period when they echo speech, so it is important to determine if the echolalia is outside the normal range. In normal children, echoing generally stops by three years of age. In autism, echoing is often persistent beyond this point, and thus abnormal.
Metaphorical language: An example of metaphorical language is using the phrase, "Go green riding," to indicate that one would like to use the swing in the garden. In this example, the metaphor could only be understood if one knew the child and the incident in which this phrase was first said. It should be noted that this is not a genuine metaphor in the sense that this term is used in linguistics.
Neologisms: Neologism literally means "new word." An example would be using the nonsense term "willip" to mean a piece of fluff. Again, neologisms are also heard in normal children's language, but these do not usually persist in the face of other people's failing to understand them, unless it is in the context of a joke.
Pronoun reversal (or difficulty with the use of pronouns): Children with autism may use "you" when they mean "I", or they may call themselves by their first name. When a teacher asks, "Have you been swimming today?" an autistic child may reply, "You been swimming today," meaning "Yes, I have been swimming."
The second core area of difficulty that determines the diagnosis of autism is a lack of flexible imagination, coupled with obsessional behavior. For example, one patient may take an obsessional interest in counting lampposts, collecting bottle-tops, and naming geometric shapes. This repetitive quality in the interests of children with autism makes their play very uncreative. So, for example, pretend play, normally seen from about 18 months onwards, in which the child creatively uses an object (using a cup as if it were a hat), is rarely seen in children with autism. If it is present at all, it is usually very limited. Its absence or limited appearance immediately alerts the professional to the possibility of autism.
The deficits in communication and inability to adapt or improvise are hallmarks of the disorder. Problems with social/communicative development and inflexible thinking are psychological, but ultimately, they have their cause in abnormalities in the brain. Understanding the links between the psychological and brain abnormalities is the focus of a great deal of research [1,3,4].
Landau-Kleffner syndrome (LKS) (or acquired epileptic aphasia) may mimic autism, with the outstanding feature being the loss of language following a period of normal development (usually between 2 and 7 years of age) [8,82]. Since the identification of LKS in 1957, only about 200 cases of the syndrome have been reported worldwide; however, LKS is difficult to diagnose and is also often misdiagnosed [68,83].
The differential diagnosis of autism and LKS is complicated by a variety of factors. Epilepsy occurs in individuals with LKS about 70% to 85% of the time. Abnormal brainwave patterns identified by EEG are central to the diagnosis . Children with autism also have higher than normal rates of epilepsy as well as abnormal EEGs. As many as 35% of individuals with autism have been identified as having a seizure disorder by the time they reach early adulthood . However, children diagnosed with autism frequently have not had an EEG, particularly an extended-sleep EEG, which can detect the pattern of abnormalities typically seen in individuals with LKS. The differential diagnosis between these two conditions may also be complicated by their common behavioral disturbances. For these reasons, it is important to rule out LKS whenever a child presents with what appears to be late-onset autism .
The prognosis for children diagnosed with LKS varies. Some have an overall poor quality of life, mostly due to language difficulties. Others may, months or years later, regain much of their language abilities, although remission and relapse is possible. Early diagnosis and prompt treatment may help to achieve better long-term prognosis [83,85,86].
Treatment may include anticonvulsant medications, adrenocorticotropic hormone (ACTH), corticosteroids such as prednisone, immunoglobulins, a ketogenic diet, or surgery . Speech therapy has also been recommended and should be started early. The prognosis is often improved when the onset of LKS occurs after the child's sixth year and when speech therapy has been initiated early .
Rett syndrome is a neurodevelopmental disorder that affects 1 in 10,000 to 15,000 female live births. It is primarily a sporadic condition, with about 1% of cases being familial. Boys who have the disorder usually die before birth or within a year . Until 1999, when a mutant gene (MECP2) was found in some patients with Rett syndrome, there was no way of making a definite diagnosis, and there were few clues about its pathogenesis . A clinical diagnosis of Rett syndrome may be made through physician observation of the child's early developmental progress and ongoing evaluations of the child's neurological status. Autistic-like behaviors are common in the early stages . Physicians will use a highly specific set of guidelines designed to confirm or negate a diagnosis of Rett syndrome. The clinical diagnosis is complemented by a specific genetic test. Nearly all cases of Rett syndrome are caused by the MECP2 mutation .
According to the National Institute of Neurological Disorders and Stroke (NINDS), there are four stages of Rett syndrome :
Stage I (early onset): This stage usually occurs between 6 and 18 months of age and may last for several months to more than a year. It may be missed because the symptoms are vague and not necessarily obvious. Infants may demonstrate less eye contact and less interest in toys. Delays in gross motor skills (i.e., sitting or crawling) may also be present. Hand wringing and decreased head growth is usually too subtle to draw attention.
Stage II (rapid destructive): This stage usually begins between one and four years of age. It generally lasts for several weeks or months and is characterized by either a gradual or swift loss of purposeful hand skills. Spoken language is lost, and the child may also display autistic-like symptoms. Characteristic hand movements (i.e., wringing, washing, clapping or tapping, and repetitious movement of the hands to the mouth) usually appear during Stage II, although they are discontinued during sleep. Breathing is also normal during sleep, but aberrations such as apnea and hyperventilation may occur when the child is awake. A decrease in head growth is usually noticed at this stage. Gait is unsteady and initiating any motor movements may be difficult. Irritability and sleep irregularities may also occur.
Stage III (plateau or pseudostationary): Occurring between 2 and 10 years of age, this stage may last for several years. Apraxia, motor difficulties, and seizures are foremost during stage III. The child may experience some improvement in behavior, with less irritability, less crying, and fewer autistic-like features. The child may also show more interest in her surroundings. Alertness, attention span, and communication skills may also improve. Many females remain in stage III for the majority of their lives.
Stage IV: (late motor deterioration): This stage is characterized by reduced mobility and may last for years or even decades. Muscle weakness, rigidity, spasticity, dystonia, and scoliosis are also prominent during stage IV. If the individual previously walked, she may no longer be able to walk at this stage. In most cases, there is no decline in cognition, communication, or hand skills. Repetitious hand movements may decrease, and eye gaze usually improves.
Most patients with Rett syndrome survive for many years, requiring complete care, and frequently develop additional medical complications related to their underlying neurodevelopmental disorder .
First, it must be stressed that issues of comorbidity are not all inclusive in this discussion. The issues are many and complex. To gain a better understanding, one must consider the concepts of comorbidity, co-occurring conditions, and behavioral symptoms .
For example, a particular genetic marker (i.e., a fragile site on the X chromosome) defines fragile X syndrome. This syndrome is associated with mental disability as well as with the social and communication dysfunctions that characterize autism. Fragile X syndrome occurs more frequently in the autistic population than chance alone would indicate . Testing for fragile X has been recommended in individuals with mental retardation, developmental delay, and autism .
Several other conditions, including epilepsy, are comorbid with autism and occur more frequently in the autistic population than in the general population. This comorbidity carries the dual implications of the likelihood of a poor prognosis as well as the possibility of its being a key to the cause of autism . In addition, obsessive-compulsive disorder (OCD) includes some of the features of autism. For example, the rituals of obsessive-compulsive individuals are similar to those often found in individuals with autism .
It is important to remember that ASD management must be individualized. Just as no autistic cases are exactly alike, there are no exact management protocols for autistic individuals. After an accurate diagnosis has been made, an individual management plan should be determined and re-evaluated as necessary. Management may include pharmacotherapy, biomedical treatments, behavior modification, and a variety of educational therapeutic techniques.
The following discussion describes some common management suggestions. It is not to be considered all-inclusive. The reader should also realize that all ASD research is dynamic, and it is important to be aware of the most current findings and results.
With the realization that biological factors are of fundamental importance in causing autism, the search for drug treatments has gained ground. As of yet, there is no drug that clearly leads to improvements in the basic symptoms of autism. As with psychological treatments, it is important to be cautious in accepting claims to the contrary. This does not mean, however, that drugs are of no use in treating certain aspects of autism. Some pharmacotherapies may have positive effects on the symptoms of autism. A number of medications have been evaluated, and the evidence for their effectiveness is briefly outlined in the following sections.
This class of medications encompasses a number of different but related drugs, such as haloperidol, chlorpromazine, and thioridazine, which are frequently used in the treatment of adults with psychiatric disorders. They are sometimes used for children with autism, not because they improve the autism itself, but because they may provide temporary relief from agitation, aggression, insomnia, stereotypies (i.e., repetitive behaviors), or other behavior problems . They are powerful drugs and may produce unwanted side effects, such as possible dystonias, akinesia, akathisia, cognitive slowing, and/or weight gain, especially if used over a long period [95,96,97,98]. Fortunately, many of these side effects reverse on stopping the treatment; occasionally, irreversible neurological problems may develop as a result of the medication. For these reasons, these drugs are mainly used to help break a maladaptive style of behavior or as a temporary adjunct to other forms of treatment .
In 2006, the U.S. Food and Drug Administration (FDA) approved the first drug for the treatment of behaviors associated with autism in children . Risperidone is in a newer class of medications called atypical antipsychotics . It has been proven by several studies to be effective in ameliorating irritable behavior in autistic children, such as aggression, deliberate self-injury, and temper tantrums [99,100,101]. The most common side effects of risperidone include increased appetite, weight gain, and sedation, with weight gain being the most significant [98,99,100,101]. The only other drug that is FDA approved for the treatment of autism is the atypical antipsychotic aripiprazole .
In preliminary studies, a few other medications in this class, including olanzapine and ziprasidone, have been shown to have similar beneficial effects [92,102,103,104]. Although they are effective in controlling behavioral symptoms, olanzapine and ziprasidone are associated with significant adverse effects, including abdominal pain, seizures, and excessive weight gain [92,98].
All atypical antipsychotic medications are associated with a high incidence of cardiometabolic side effects, such as age-inappropriate weight gain, hypertension, lipid and glucose abnormalities, and obesity . These are particularly problematic during childhood, as they are strong predictors of adult obesity, metabolic syndrome, and cardiovascular morbidity and malignancy. The risk versus benefit of antipsychotic therapy must be thoroughly assessed when considering long-term use.
Seizures occur in approximately 25% of persons with ASD, with the occurrence being much higher in those that have low IQs or are mute . Although anticonvulsants cannot always eliminate seizures, they may reduce the number of seizures that occur. The smallest amount of medication that is effective should be used. Anticonvulsants commonly used are carbamazepine, lamotrigine, topiramate, and valproic acid .
Stimulants such as methylphenidate are sometimes used to address symptoms such as hyperactivity, impulsivity, disinhibition, and inattention [93,97,105]. These medications are not as effective in treating these symptoms in individuals with ASD compared to those with ADHD, but they may be effective in children with less severe autism . Adverse effects are also more common in children with autism compared to those with ADHD.
Although it is unclear if these medications are useful for treating ASD symptoms, antidepressants typically prescribed to treat depression and anxiety (e.g., fluoxetine, sertraline, citalopram) may also be prescribed to reduce aggression and repetitive behaviors in autistic individuals . A 2009 study suggested that citalopram was not effective at reducing repetitive behaviors in children with ASD . A 2010 Cochrane review concluded that there is no benefit, and emerging evidence of harm, with selective serotonin reuptake inhibitors in the treatment of ASD .
Several other medications may be used to treat ASD symptoms, including naltrexone, lithium, diazepam, and lorazepam . The safety and efficacy of these medications have not been indisputably proven for autistic children. As each individual's ASD symptoms will vary greatly, his or her response to pharmacological treatment will vary as well. Minimal dosages and caution should be used.
Secretin is a polypeptide neurotransmitter involved in digestion. It may be given during an endoscopy to assess digestive function, which is a medical condition common among many individuals with autism. The first clinical trial of secretin to report results found that the hormone was no better than a placebo in improving symptoms of children with autism. Clinical trials conducted in the last few years have produced similar results .
Anecdotal reports of the success of secretin have prompted a growing number of parents eager for a cure to seek out medical professionals willing to try the hormone on their child. However, secretin has not been approved by the FDA to treat autism, nor is it recommended by the National Institutes of Health (NIH) .
A meta-analysis reported by the Cochrane Collaboration found no evidence that intravenous secretin, either in single or multiple doses, had any effect on function, behavior, core features, or quality of life for autistic patients . Researchers concluded that the hormone should not be administered as part of the treatment plan for autistic patients.
Drugs for the treatment of Candida infections and various alternative therapies (e.g., homeopathy, cranial osteopathy) have been advocated for the treatment of autism. None of these treatments have been shown to be effective, although mainstream medical practitioners often have not formally evaluated these therapies. Many are not in themselves harmful, and in some instances, beneficial effects may result from changes in the parents' sense of involvement in the therapy. However, whatever changes these therapies do produce, there is no evidence that they amount to a cure. Systematic and independent evaluation of treatment is emphasized due to the dangers of unsystematic appraisal of therapies. Unsystematic appraisal may lead to parents' hopes being raised unrealistically. Hope must be based on reasonable evidence [3,4,114].
Some believe that dietary changes and/or high-dose vitamin treatments may improve core behaviors and certain symptoms associated with ASD. The theory holds that the autistic brain lacks the proper nutrition, due perhaps to genetic and/or physiological variations . Other biomedical treatments, such as antifungal therapy, chelation, glutathione therapy, and melatonin supplementation, are also purported to improve certain ASD symptoms by reducing toxic load or correcting hormone levels.
While there are studies that support various biomedical treatment approaches, there are many that do not show evidence of improvements. Some believe that when the right combination/cumulative effect is reached, these interventions have at least as much impact on functioning compared to other (i.e., pharmacologic) treatment modalities. Dietary modifications/supplementations are generally regarded as safe, with a minimal potential for adverse effects; however, the cost of foods and supplements, time expenditure, and the close monitoring of small changes needed to tune the treatment may not suit all parents. A willingness or eagerness must preclude the expectation that a parent follow such a course, as there is very limited evidence to justify the additional burden. Certain case studies and anecdotes do show significant improvements in ASD symptoms with various biomedical approaches. The Autism Society describes several of these interventions in the order which they are generally recommended and the rationale for their recommendation :
Improved diet: A complete, balanced diet free from excessive "empty" calories, artificial colors, artificial sweeteners, trans-fats, and preservatives is essential for maintaining stores of nutrients and overall health.
Reduce food sensitivities: Avoiding certain foods can reduce allergic/inflammatory response. Behavior and attention may be improved with this intervention.
Gluten-free and casein-free diet: This type of diet may be recommended because these substances are common allergens and proinflammatory sources.
Vitamin/mineral supplements: A balanced multivitamin has been shown to improve sleep patterns and gut function. Boosting levels of key nutrients lacking in the diet, most notably vitamin C, may reduce oxidative stress, which is common in autistic individuals.
Essential fatty acids: Low levels of essential fatty acids are implicated in several psychological disorders. Two of the major omega 3 fatty acids, DHA and EPA, are critical for early and later brain development, respectively.
Digestive enzymes: The use of digestive enzymes may provide greater benefit from nutrition by replacing insufficient or lacking enzymes, which are common in autistic individuals.
Gut treatments: Some children with autism have low levels of beneficial bacteria and high levels of toxin-producing fungi; treatments include an antifungal diet, antifungal medications, and/or the inclusion of probiotics.
Amino acids: Supplementation with amino acids may be beneficial for children with self-limited diets or for those unable to properly digest proteins into amino acids. Because they are the building blocks of antibodies, enzymes, hormones, immunoglobulins, glutathione, neurotransmitters, and many other substances, proper levels of amino acids are essential for proper brain function.
Melatonin: Melatonin supplementation can lead to improved sleep in autistic children. Because melatonin is produced during sleep in a dark room, the lack of sufficient sleep can compound the problem.
Thyroid supplements: One study found that a high percentage of children with autism may have low thyroid levels. Increased iodine intake may boost thyroid hormone levels, but persistent hypothyroidism warrants thyroid supplementation.
Glutathione: Many children with autism have low levels of active glutathione, which is needed to protect the body from many toxins, including toxic metals. Low glutathione levels in these patients are related to genetic abnormalities in the methionine pathway.
Chelation: Because of low glutathione levels, many children with autism have higher toxic burdens, including heavy metals and other hazardous chemicals. Although mercury and other toxins are not definitively known to cause autism, a reduction of ASD symptoms following chelation therapy has been exhibited in anecdotes and case studies.
Immune system regulation: There is some evidence for autoimmunity in ASD patients. Possible treatments for immune system regulation include intravenous immunoglobulins (IVIG), low-dose naltrexone, and pioglitazone. IVIG has been shown to significantly improve many autistic behaviors and symptoms in several studies, but most patients regress when the expensive treatment is discontinued. Naltrexone for autism (0.5–2 mg/kg/day) has been the focus of several clinical trials. Reduction in self-injurious behavior is considerable, and naltrexone may also attenuate agitation, hyperactivity, irritability, temper tantrums, social withdrawal, and stereotyped behaviors. In one small study (25 children), pioglitazone was shown to reduce hyperactivity, irritability, lethargy, and stereotypy, but it was less effective for older children.
High-dose vitamin B6 and magnesium supplementation has been the focus of at least 20 studies, including 12 double-blind, placebo-controlled studies. The consensus is that roughly half of autistic children and adults benefit from this megavitamin combination . More than 100 enzymatic reactions require vitamin B6 (e.g., production of major neurotransmitters [dopamine, serotonin] and glutathione). If vitamin B6 is taken by itself, hyperactivity can occur; magnesium is used to prevent this possibility. Most studies used vitamin B6 dosages of about 8–15 mg/lb (maximum: 1000 mg) . A dose of at least 6 mg/lb is typically necessary for any noticeable benefit.
In addition to vitamin B6 and magnesium, B12 and cod liver oil have been studied for their possible effects on the characteristic symptoms of autism, with mixed study results [97,108,109,110]. Conversely, when vitamin B6 is stopped, withdrawal effect may occur and be mistaken as evidence for the effectiveness of the vitamin. In addition, while unwanted side effects from vitamin B6 are rare, there is evidence that it may cause side effects in conjunction with magnesium, large doses of other vitamins, or antiepileptic medication. Furthermore, large doses of some vitamins and minerals may be toxic. As with any dietary modification, it is recommended that megavitamin treatment be used only under specialist medical supervision [3,4,111].
It has been suggested that gluten-free and casein-free diets may improve digestion and lessen food intolerances or allergies in autistic children. However, it is very difficult to follow such diets because gluten and casein are found in wheat, oat, rye, barley, and milk . Also, removing gluten and casein from the diet may cause side effects and should only be done with the advice of a healthcare professional [3,112]. It is important to note that clinical evidence for the efficacy of dietary restrictions is lacking and that a direct relationship between autism and food ingestion has not been established [112,113].
In the years since autism was first described, a range of different psychological treatments have been tried. While there have been no independently assessed demonstrations of an absolute cure, different types of psychological treatment have had considerable beneficial effects. While the clearest example is behavior therapy, other therapies may also help the individual with an ASD progress.
Behavioral programs are designed by psychologists and psychiatrists working in consultation with parents, teachers, and/or care staff, and are ways of shaping adaptive behaviors or decreasing maladaptive behaviors. As such, behavior therapy can be of immense practical value. In behavior therapy, the behavior is analyzed into its causes and consequences, and then a behavioral program is implemented. The approaches most beneficial to children with ASD provide structure, direction, and organization and allow for family members to participate .
There are different types of behavior modification used to treat behaviors that are inappropriate (e.g., self-injury, tantrums), repetitive, or aggressive. Most behavior modification methods are founded on the applied behavior analysis (ABA) theory. ABA has become widely accepted and its use adopted in the United States [3,108]. This theory holds that behavior that is rewarded appropriately is more likely to be repeated than behavior that is ignored. Positive behavior is encouraged and negative behavior is discouraged, with the end-goal being improvement in the child's skills [3,112]. Behavior modification includes highly structured, skill-oriented activities that are based on the individual patient's needs and interests. This requires intense, one-on-one training with a therapist as well as parental involvement . Examples of ABA include :
Discrete trial training, which is designed to teach each step of a desired behavior
Early intensive behavioral intervention, which is most often used in very young children
Pivotal response training, which strives to increase the child's motivation and self-monitoring capabilities
Verbal behavior intervention, which focuses on improving the child's verbal skills
Behavior modification is beneficial and may assist individuals with ASD to function in daily life. However, it fails to significantly affect social and communicative deficits because these are complex, unique to each situation, and do not solely depend on single behaviors that can be increased or decreased .
A lack of "theory of mind" refers to the general manner in which many autistic individuals do not understand other people. That is, they lack the ability to understand another's perspective. They are not aware that others have their own thoughts, plans, beliefs, attitudes, emotions, and points of view . Autistic individuals are not able to understand social cues or interpret facial expressions, body language, or tone of voice. These social skill deficiencies culminate into a lack of empathy or sensitivity to others' thoughts and feelings and prove very difficult to teach .
Social skills training includes a broad range of techniques that are used to help teach social interaction skills to individuals with autism so they can navigate social reality . This is painstaking work for the teacher or therapist, given the complexity of most social skills, but it is an essential component of education and treatment and critical to success in the classroom, workplace, and community. The individual with ASD may need social skills training during childhood and well into adulthood, and the training needs will vary from one developmental stage to the next .
Examples of this type of training include teaching adolescents with autism how to make phone calls, how to go shopping, or how to behave on public transportation. In each case, it is not the physical aspects of the task (e.g., how to dial the phone-number or how to count the money) that necessarily pose the difficulties, but the social conventions that surround these (e.g., how to start, maintain, and finish the phone call; how to wait politely for one's turn in the supermarket check-out; or how not to stare at people on the bus).
A few of the better known techniques involved in social skills training include :
Social stories: Brief, personal stories written specifically for the child to help him/her understand a particular social situation.
Comic strip conversations: Conversations that are "drawn" to help the child learn the social rules that others learn naturally
Hidden curriculum: Strategies that directly teach unspoken (hidden) social rules, which most people pick up and understand intuitively
Social scripts: Creating and teaching specific "scripts" that the child may use in day-to-day social situations
Computers and other technology: Videos, software, or virtual-reality programs used to teach the more complex social skills (e.g., recognizing facial expressions)
Social skills groups: Groups wherein the ASD individual can practice social skills
Although there is some evidence that these treatments are common, especially among older and higher functioning children with ASD, limited research has been done on the efficacy of these treatments .
While the value of psychotherapy will depend on the kind of therapy tried, its main value in the context of autism is in providing supportive counseling during difficult periods, including periods of depression that may arise. Psychotherapy is unlikely to benefit autistic individuals who have insufficient language skills. Play therapy is an alternative nonverbal technique that may help children with autism control anxiety and play more creatively .
Speech and language therapy is another specialist therapy that is found in many schools and units for autism. It is considered essential for any child with speech or language difficulties . The Individuals with Disabilities Education Act (IDEA) has mandated surveillance and screening for children with disabilities. Infants and toddlers (birth through 35 months of age) are to receive early intervention services. Children 36 months of age and older are to be referred for free, appropriate public education .
Speech-language pathologists work on several areas of language development, including articulation, phonology, morphology, syntax, semantics, pragmatics, fluency, and prosody . However, despite intensive individual treatment, spontaneous and appropriate conversational speech may continue to be difficult for many people with autism. The therapy setting should evolve over time to meet the changing needs of the child . Conversational skills may need to be encouraged in more natural settings, such as while playing at home. It may also be that speech therapy at an early stage in development would have more impact. This remains to be tested .
The picture exchange communication system (PECS) is an alternative/augmentative communication system developed to help children with limited speech attain functional communication . Many autistic individuals think in pictures rather than words . As a result, they often respond to visual prompts, pictures, and photographs rather than verbal directions. PECS helps autistic patients communicate using picture cards that represent ideas and activities, or by using other items that convey their requests, needs, and desires. Studies have shown that patients can learn to use the PECS quickly and efficiently . Although it was thought that using pictures to communicate would impede language performance, the system has been found to improve language skills .
Occupational therapy is effective in facilitating independence in autistic patients. It addresses areas that interfere with the patient's ability to perform everyday tasks [32,120,121]. Children are assessed in terms of age-appropriate life tasks, such as buttoning a shirt, eating, and bathing . In general, occupational therapy benefits the autistic patient by attempting to improve overall quality of life.
Physical therapy uses physical measures such as exercise, massage, and heat to help patients develop coordination and improve body movements and awareness. Autistic patients may suffer from low muscle tone and other physical limitations. Physical therapy can help build or restore strength, mobility, and motor skills [97,108,122].
Sensory integration therapy assists autistic patients in coping with sensory stimulation, because some children may have sensitivities to certain textures or sounds that can prompt undesired behaviors or actions . Sensory integration is the neurological process of organizing information received from the body and external stimuli into a productive set of cues. Sensory integration therapy helps improve the patient's behavior and motor development and may include having the patient handle items with different textures or listen to different sounds [108,123]. The sensory input is then coupled with physical activity or a positively-reinforced behavior. Although it does not directly teach higher-level skills, sensory integration therapy provides a basis for the child to learn more complex material .
Play therapy may also be referred to as imaginative, symbolic, or non-directive play therapy [124,125]. Autistic children are often described as missing the curiosity of children with typical development. Their play behavior is often limited to simple manipulation. For example, when playing with a toy car, they may be more interested in spinning the wheels of the car than playing a driving or racing game . Play therapy includes adult-child interaction that is controlled by the child and used to improve emotional development, thereby improving social skills and learning ability . Benefits may also include increased independence and empathy .
Incontinence may represent a major problem in some children with autism. Careful assessment of the causes of the wetting or soiling is important. For example, it may result from a delay in the acquisition of bladder and bowel control, in which case toilet training may be helpful. For night wetting, a method such as the "bell and pad" may be appropriate. Such programs should be carefully tailored to the individual, and parents should ask to be referred to a specialist clinic. A few children with autism develop the habit of smearing feces, and this requires a clear and consistent behavior program (i.e., rewarding him or her for not doing it) if the child fails to learn its unacceptability .
Fortunately, most people with autism do not show excessive aggression, although they naturally show anger, just as other people do, at times of frustration. Nevertheless, certain kinds of aggression are sometimes seen in children with autism. Teaching about the other person's feelings may help to manage aggression; a more direct and simple method involves rewarding alternative, non-aggressive behavior. Again, a psychologist or therapist should be consulted to help to achieve this .
Doing embarrassing things is another sign of the social naiveté of many children with autism. When this occurs, it is neither willful nor deliberate, as some people may at first think, nor is it designed to annoy, as many parents might imagine. It is simply a reflection of the severe inability most people with autism have in appreciating the thoughts and feelings of others. Examples of embarrassing behavior commonly reported to occur in autism include: saying the wrong thing at the wrong time (e.g., truthfully commenting that the teacher's gray hair now looks blacker); doing the wrong thing at the wrong time (e.g., rubbing their genitals conspicuously during the school Christmas party); or simply being oblivious of the social norms that implicitly govern particular situations (e.g., staring at people on the train). Teaching proper behavior can only be done at the time that the embarrassing behavior occurs and should be reinforced with examples. As previously discussed, social skills training requires intensive individual work because, for many people with autism, sensitivity to social cues does not come naturally .
The most effective treatment for self-injury, such as head banging, biting, and hitting oneself, is based on a careful evaluation of the factors that both trigger and help to maintain the self-injury. Behavior therapy is the most useful form of intervention. Protective devices, such as helmets, arm-splints, and gloves, may be used temporarily to prevent severe damage to the head or body until the self-injury has been controlled by psychological intervention .
Pica (i.e., eating, and swallowing inedible substances such as earth, stones, glass, and paint) may be evident in children with autism and can be problematic. A physical examination should be carried out to check if medical conditions (e.g., iron deficiency, lead poisoning, zinc deficiency) are causing the behavior or if complications (e.g., intestinal damage, obstruction, infestation) have developed. Treatment of associated medical conditions can then be implemented and may lead to a reduction in the behavior. Otherwise, ABA, based on rewarding the eating of edible substances, is most appropriate.
Aside from pica, another common eating difficulty is excessively fussy eating (e.g., only eating certain foods or only eating a food if it is always arranged in exactly the same way on the plate). This may represent one instance of a person's obsessive, ritualistic behavior. Such obsessive eating styles are often maintained because parents and others want to avoid the tantrum they know will follow if the food is not prepared according to the child's wishes. Such a response is understandable; however, inflexible eating habits are sometimes impossible to satisfy, so it is worth attempting to change the child's eating behavior toward greater flexibility at the earliest opportunity. This may be achieved by introducing only minute quantities of foods that the child refuses to eat, or by gradually, minutely changing the arrangement of the food until a range of foods or arrangements is tolerated. The alternative approach is to implement a big change quickly and then weather the tantrum this may provoke. When the child discovers that tantrums do not bring a return of the favorite food or plate, the tantrums may eventually subside, especially if the child is hungry. Caution is required, however, as occasional attempts at self-starvation have been seen .
Formerly, it was thought that children with autism were not educable. Such attitudes resulted in children with autism being placed in the back wards of long-stay mental institutions, and their lack of progress was then taken as proof of their inability to be educated. Evidence now suggests that few, if any, children are not educable, whatever their intellectual level. The overriding principle is that education should be tailored to the unique needs of the individual. Educability is evident in the progress made, whatever its rate [4,126,127].
Highly structured teaching programs have claimed to produce the greatest results in children with autism, for three main reasons. First, the social problems associated with autism are such that if a teacher is not actively initiating interaction and being directive, a child may simply drift away from social contact to pursue repetitive patterns of behavior. These repetitive behaviors, by definition, allow very little learning of new information. Secondly, the highly structured approach starts from the assumption that every task should be broken down into simple and clear steps, with each goal clearly defined. Children with autism seem to take to such a methodical approach. Finally, highly structured teaching may better prepare children with autism for the "real world." Certainly, attempts to teach social skills in an inflexible way can be self-defeating, as normal social behavior is by definition inherently flexible [4,126,128,129].
Children with autism may revert to their own repetitive activities or solitary existence if they do not receive individual attention. Some children with autism are able to work individually without anyone sitting at their side, in some cases for long periods of time. However, this ability may develop quite late in some children and may need to be specifically taught. To maintain their attention sufficiently for learning to occur, a ratio of 3 pupils to 1 teacher seems appropriate. However, smaller school classrooms for autism have found that a direct one-to-one teacher-pupil ratio is ideal, if resources allow [4,130,131].
Even with as little as two years of schooling, children with autism improve considerably in their educational development. Those who make educational progress tend to have the best outcomes, although their IQ at five years of age is an important predictor of their eventual attainment. For those children with average or above-average IQs, academic attainments may be normal. Some adults with autism have even gone through higher education and achieved college degrees. Temple Grandin, who holds a PhD in Agricultural Science and who has written a book about her personal experience of autism, is a rare example of such achievement [4,132].
Communication problems are central to ASD. All individuals with autism experience some form of difficulty in comprehending verbal and nonverbal communication and, therefore, special care must be taken to know what each person understands and how to best give messages. The ideal outcome is for children with autism to utilize language and communication in a variety of situations .
Messages are conveyed through tone of voice, gestures, body language, and choice of words. Consider using visual means to convey information whenever possible, as visual information is more concrete and may help clarify the message.
The following general techniques are helpful :
Understand the difference between the person's comprehension and expressive abilities.
Learn about the individual before engaging in your first exchange.
Be concrete, direct, and specific; avoid subtleties.
Avoid threats or reprimands; emphasize what should be done and what the reward for completing the task will be.
Clarify your message with visual and/or gestural supports, if needed.
Provide background information to enhance comprehension, as needed.
Repeat and/or restate messages positively, but directly.
Avoid creating tension or stress in the individual, which may interfere with communication.
Avoid prolonged interactions; keep them brief and positive.
Sign language is used in some cases to help build communication in those children with speech difficulties. This is done to improve expression; if their speech is undeveloped and incoherent, a manual sign may often clarify which word they are using. It is also done to improve understanding of someone else's speech. In the latter case, it is argued that signs are more concrete and simpler to understand than spoken words. Signing can be a great tool for children with autism by making it easier for them to discover the meaning of language and thereby skip some of the difficulties presented by vocal communication. However, sign language is best used as an aid to developing communication and speech. If it is taught as an end in itself, its obvious disadvantage is that the child is restricted to communicating only with those who can understand signing. Therefore, speech should be thought of as the communicative medium to teach and signing as a stepping-stone toward this goal. It is important to note, however, that as many as 25% of children with autism never develop verbal language skills. For these children, sign language may be vital [4,131,134].
The following discussion will consider the range of outcomes that usually occurs in people with autism. This by no means defines the limits, but attempts to summarize the kinds of outcomes that may be expected.
Our knowledge is limited by the fact that very few studies have followed people with autism into their later adult life and by the fact that elderly people known to have autism are rare, as the disorder itself was only rarely diagnosed until the later 1900s. We do know, however, that the range of outcomes is very wide, especially for children with severe autism. For people with autism who also have severe mental handicap, some sort of life-long support and supervision will be essential. For more able individuals, the outcome depends on how much useful language the person has acquired. Generally, children with autism that develop verbal language before five or six years of age have a considerably better prognosis. The less language a person has, the more support that person will need. It is, however, important to note that language can develop as late as adolescence, although the rate of development by this age may be slow and limited [4,66].
For the most able people with autism, a life of independence and employment in the open marketplace is not unprecedented, but it is unusual. A very small proportion of children with autism go on to lead independent adult lives. Sheltered accommodation and employment is more usual. Other options include day centers, in which individuals are given interesting activities and some training but may not be employed. A majority of people with autism continue to live with family members [4,67].
There are some worrying reports of an overall decline or deterioration in a small minority of people with autism beginning during puberty. While the majority of people with autism fortunately continue to learn and develop intellectually and in other ways well into adulthood, some do begin to decline. This is evidenced by a slow in learning and a decrease in IQ test scores. In a certain percentage of people, this cognitive slowing is marked by the onset of epilepsy, which occurs for the first time at this stage. These changes, it should be stressed, only occur in a minority of people. Most adolescents do not show deterioration, and the worry instead becomes centered on how the intensive support and educational benefit that was coming from the school can continue when the adolescent leaves school .
Early and accurate diagnosis of autism is crucial. Early intervention, including appropriate programs and support, can facilitate progress toward a meaningful and productive life for autistic children and adults. A study completed in metro Atlanta established that, on average, children with autism experience a 13-month delay between evaluation and diagnosis. The study also found that as many as 70% of healthcare professionals failed to utilize a standardized diagnostic tool. These statistics emphasize the importance of educating healthcare professionals on the signs of autism and encouraging the use of standardized diagnostic instruments when developmental delays or autism are suspected .
If the initial screenings indicate the likelihood of autism, it is important that the child is evaluated by a specialist, who may determine the extent to which the child has (additional) disability. This information is essential in planning realistically for the child's future and will affect the kind of school to be chosen .
Thankfully, a number of organizations promote autism awareness, education, and research. A brief listing of these organizations follows. Many have local chapters. Interested persons are encouraged to visit the following websites or contact the association for more information.
|Advancing Futures for Adults with Autism|
|Association for Science in Autism Treatment|
|P.O. Box 3250|
|Hoboken, NJ 07030|
|Association for Behavioral Analysis International|
|550 West Centre Avenue|
|Portage, MI 49024|
|Autism National Committee (AUTCOM)|
|Autism Research Institute|
|4182 Adams Avenue|
|San Diego, CA 92116|
|4340 East-West Hwy, Suite 350|
|Bethesda, MD 20814|
|1 East 33rd Street, 4th Floor|
|New York, NY 10016|
|Indiana Institute on Disability and Community|
|1905 North Range Road|
|Bloomington, IN 47408|
|Kennedy Krieger Institute Interactive Autism Network|
|First Signs, Inc.|
|P.O. Box 358|
|Merrimac, MA 01860|
|Global Autism Collaboration|
|National Institute on Deafness and Other Communication Disorders|
|31 Center Drive, MSC 2320|
|Bethesda, MD 20892|
|Eunice Kennedy Shriver National Institute of Child Health and Human Development|
|31 Center Drive|
|Bldg 31, Room 2A32|
|Bethesda, MD 20892|
|National Institute of Mental Health|
|6001 Executive Boulevard|
|Room 6200, MSC 9663|
|Bethesda, MD 20892|
|National Center on Birth Defects and Developmental Disabilities|
|National Institute of Neurological Disorders and Stroke Autism Information Page|
|Online Asperger Syndrome Information and Support Center|
|Organization for Autism Research|
|2000 North 14th Street, Suite 240|
|Arlington, VA 22201|
1. National Institute of Child Health and Human Development. Autism Spectrum Disorder (ASD). Available at http://www.nichd.nih.gov/health/topics/autism/Pages/default.aspx. Last accessed November 5, 2013.
3. Centers for Disease Control and Prevention. Autism Spectrum Disorders (ASDs): Data and Statistics. Available at http://www.cdc.gov/ncbddd/autism/data.html. Last accessed November 7, 2013.
5. Kaneshiro NK, Zieve D. Autism. Available at http://www.nlm.nih.gov/medlineplus/ency/article/001526.htm. Last accessed November 7, 2013.
6. Centers for Disease Control and Prevention. Mental health in the United States: parental report of diagnosed autism in children aged 4–17 years—United States, 2003–2004. MMWR. 2006;55(17):481-486.
7. Remedy Health Media. Autism Overview. Available at http://www.healthcommunities.com/autism/children/overview-of-autism.shtml. Last accessed November 7, 2013.
8. Cohen S. Targeting Autism: What We Know, Don't Know, and Can Do to Help Young Children With Autism Spectrum Disorders. 3rd ed. Berkeley, CA: University of California Press, Ltd.; 2006.
9. Grandin T, Scariano MM. Emergence: Labeled Autistic. 1st ed. New York, NY: Warner Books Edition; 1996.
10. National Network for Immunization Information. Measles, Mumps, Rubella (MMW). Available at http://www.immunizationinfo.org/vaccines/rubella#toc-top. Last accessed November 7, 2013.
11. Yamashita Y, Fujimoto C, Nakajima E, Isagai T, Matsuishi T. Possible association between congenital cytomegalovirus infection and autistic disorder. J Autism Dev Disord. 2003;33(4):455-459.
12. Weiss LA. Autism genetics: emerging data from genome-wide copy-number and single nucleotide polymorphism scans. Expert Rev Mol Diagn. 2009;9(8):795-803.
13. Geier DA, Geier MR. Early downward trends in neurodevelopmental disorders following removal of thimerosal-containing vaccines. J Am Phys Surg. 2006;11(1):8-13.
14. American Academy of Pediatrics. Immunization: Thimerosal. Available at http://www2.aap.org/immunization/families/ingredients.html#thimerosal. Last accessed November 7, 2013.
15. Geier MR, Geier DA. Neurodevelopmental disorders after thimerosal-containing vaccines: a brief communication. Exp Biol Med. 2003;228(6):660-664.
16. Medscape Medical News. Autism "Epidemic?" A Newsmaker Interview with Morton Ann Gernsbacher, PhD, and Craig J. Newschaffer, PhD. Available at http://www.medscape.com/viewarticle/508429. Last accessed November 7, 2013.
17. Rice C, Nicholas J, Baio J, et al. Changes in autism spectrum disorder prevalence in 4 areas of the United States. Dis Health J. 2010;3(3):186-201.
18. American Academy of Pediatrics. Scientific Panel Rejects Vaccines as Cause of Autism. Available at http://www2.aap.org/advocacy/releases/mayvaccineautism.htm. Last accessed November 7, 2013.
19. National Academy of Sciences. Link Between Neurodevelopmental Disorders and Thimerosal Remains Unclear. Available at http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=10208. Last accessed November 7, 2013.
20. National Academy of Sciences. MMR Vaccine and Thimerosal-Containing Vaccines Are Not Associated with Autism, IOM Report Says. Available at http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=10997. Last accessed November 7, 2013.
21. Institute of Medicine of the National Academies Immunization Safety Review Committee. Immunization Safety Review: Vaccines and Autism. Available at http://www.iom.edu/Reports/2004/Immunization-Safety-Review-Vaccines-and-Autism.aspx. Last accessed November 7, 2013.
22. Schechter R, Grether JK. Continuing increases in autism reported to California's development services system: mercury in retrograde. Arch Gen Psychiatry. 2008;65(1):19-24.
23. Centers for Disease Control and Prevention. Concerns about Autism: CDC Statement on Autism and Thimerosal. Available at http://www.cdc.gov/vaccinesafety/Concerns/Autism/Index.html. Last accessed November 7, 2013.
24. Gillberg C, Coleman M. The Biology of the Autistic Syndromes. 3rd ed. London: Mac Keith Press; 2000.
25. Chakrabarti S, Fombonne E. Pervasive developmental disorders in preschool children. JAMA. 2001;285(24):3093-3099.
26. Chudley AE, Gutierrez E, Jocelyn LJ, Chodirker BN. Outcomes of genetic evaluation in children with pervasive developmental disorder. J Dev Behav Pediatr. 1998;19(5):321-325.
28. Sadakata T, Washida M, Iwayama Y, et al. Autistic-like phenotypes in CADPS2-knockout mice and aberrant CADPS2 splicing in autistic patients. J Clin Invest. 2007;117(4):931-943.
29. Rosenberg RE, Law K, Yenokyan G, McGready J, Kaufmann WE, Law PA. Characteristics and concordance of autism spectrum disorders among 277 twin pairs. Arch Pediatr Adolesc Med. 2009;163(10):907-914.
30. Steinman L. Elaborate interactions between the immune and nervous systems. Nat Immunol. 2004;5(6):575-581.
31. Volkmar F, Siegel M, Woodbury-SmithM, et al. Practice parameter for the assessment and treatment of children and adolescents with autism spectrum disorder. J Am Acad Child Adolesc Psychiatry. 2014;53(2):237-257.
32. American Academy of Neurology. Autism Guideline for Clinicians. Available at http://tools.aan.com/professionals/practice/guidelines/guideline_summaries/Autism_Guideline_for_Clinicians.pdf. Last accessed December 2, 2013.
33. Richler E, Reichert JG, Buxbaum JD, McInnes LA. Autism and ultraconserved non-coding sequence on chromosome 7q.Psychiatr Genet. 2006;16(1):19-23.
34. Curran LK, Newschaffer CJ, Lee LC, Crawford SO, Johnston MV, Zimmerman AW. Behaviors associated with fever in children with autism spectrum disorders. Pediatrics. 2007;120(6):e1386-e1392.
35. Zhao X, Leotta A, Kustanovich V, et al. A unified genetic theory for sporadic and inherited autism. PNAS. 2007;104(31):12831-12836.
36. Tuberous Sclerosis Alliance. TSC and Autism Spectrum Disorders. Available at http://www.tsalliance.org/pages.aspx?content=604. Last accessed December 2, 2013.
37. Tuberous Sclerosis Alliance. What is TSC? Available at http://www.tsalliance.org/pages.aspx?content=2. Last accessed December 2, 2013.
38. The National Fragile X Foundation. Autism and Fragile X Syndrome. Available at http://www.nfxf.org/html/autism_and_fragile_ x_syndrome.htm. Last accessed December 2, 2013.
39. Palmer CA. Mobius Syndrome. Available at http://emedicine.medscape.com/article/1180822-overview. Last accessed December 2, 2013.
40. Larsson HJ, Eaton WW, Madsen KM, et al. Risk factors for autism: perinatal factors, parental psychiatric history, and socioeconomic status. Am J Epidemiol. 2005;161(10):916-925.
41. Kolevzon A, Gross R, Reichenberg A. Prenatal and perinatal risk factors for autism. Arch Pediatr Adolesc Med. 2007;161:326-333.
42. Durkin MS, Maenner MJ, Newschaffer CJ, et al. Advanced parental age and the risk of autism spectrum disorder. Am J Epidemiol. 2008;168(11):1268-1276.
43. Glasson EJ, Bower C, Petterson B, de Klerk N, Chaney G, Hallmayer JF. Perinatal factors and the development of autism: a population study. Arch Gen Psychiatry. 2004;61(6):618-627.
44. Auyeung B, Baron-Cohen S, Ashwin E, Knickmeyer R, Taylor K, Hackett G. Fetal testosterone and autistic traits. Br J Psychol. 2009;199(pt 1):1-22.
45. DeStefano F, Chen RT. Autism and measles-mumps-rubella vaccination: controversy laid to rest? CNS Drugs. 2001;15(11):831-837.
46. Miller E. Measles-mumps-rubella vaccine and the development of autism. Semin Pediatr Infect Dis. 2003;14(3):199-206.
47. Lintas C, Altieri L, Lombardi F, Sacco R, Persico AM. Association of autism with polyomavirus infection in postmortem brains.J Neurovirol. 2010;16(2):141-149.
48. Nordin J, Anderson R, Anderson R, et al. Immunizations. Bloomington, MN: Institute for Clinical Systems Improvement; 2012. Available at http://www.guideline.gov/content.aspx?id=36813. Last accessed December 4, 2013.
49. Courchesne E, Carper R, Akshoomoff N. Evidence of brain overgrowth in the first year of life in autism. JAMA. 2003;290(3): 337-344.
50. Hazlett HC, Poe M, Gerig G, et al. Magnetic resonance imaging and head circumference study of brain size in autism: birth through age 2 years. Arch Gen Psychiatry. 2005;62(12):1366-1376.
51. Hrdlicka M. EEG abnormalities, epilepsy and regression in autism: a review. Neuro Endocrinol Lett. 2008;29(4):405-409.
52. Rippon G, Brock J, Brown C, Boucher J. Disordered connectivity in the autistic brain: challenges for the "new psychophysiology." Int J Psychophysiol. 2007;63(2):164-172.
53. Di Martino A, Shehzad Z, Kelly C, et al. Relationship between cingulo-insular functional connectivity and autistic traits in neurotypical adults. Am J Psychiatry. 2009;166(8):891-899.
54. Janusonis S. Origin of the blood hyperserotonemia of autism. Theoret Biol Med Modelling. 2008;5:10.
55. Anderson BM, Schnetz-Boutaud NC, Barlett J, et al. Examination of association of genes in the serotonin system to autism. Neurogenetics. 2009;10(3):209-216.
56. Connors SL, Matteson KJ, Sega GA, Lozzio CB, Carroll RC, Zimmerman AW. Plasma serotonin in autism. Pediatr Neurol. 2006;35(3):182-186.
57. Piven J, Tsai GC, Nehme E, Coyle JT, Chase GA, Folstein SE. Platelet serotonin, a possible marker for familial autism. J Autism Dev Disord. 1991;21(1):51-59.
58. Betancur C. Corbex M, Spielewoy C, et al. Serotonin transporter gene polymorphisms and hyperserotonemia in autistic disorder. Mol Psychiatry. 2002;7(1):67-71.
59. Huang CH, Santangelo SL. Ausitm and serotonin transporter gene polymorphisms: a systematic review and meta-analysis.Am J Med Genet B Neuropsychiatr Genet. 2008;147B(6):903-913.
60. Yasuhara A. Correlation between EEG abnormalities and symptoms of autism spectrum disorder (ASD). Brain Dev. 2010;32(10):791-798.
61. Sundaram SK, Kumar A, Makki MI, Behen ME, Chugani HT, Chugani DC. Diffusion tensor imaging of frontal lobe in autism spectrum disorder. Cereb Cortex. 2008;18(11):2659-2665.
62. World Health Organization. International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10). 2nd ed. Geneva; World Health Organization; 2004.
63. Earls M, Curry E. The New AAP Autism Screening Guidelines. Available at http://www2.aap.org/qualityimprovement/quiin/PreSIP/Autism.pptx. Last accessed December 2, 2013.
64. American Speech-Language-Hearing Association. Selective Mutism. Available at http://www.asha.org/public/speech/disorders/selectivemutism.htm. Last accessed December 2, 2013.
65. American Academy of Child and Adolescent Psychiatry. Reactive Attachment Disorder: Facts for Families. Available at http://www.aacap.org/AACAP/Families_and_Youth/Facts_for_Families/Facts_for_Families_Pages/Reactive_Attachment_Disorder_85.aspx. Last accessed December 2, 2013.
66. Emory Autism Center. Characteristics of Autism and the Pervasive Developmental Disorders (PDD). Available at http://www.psychiatry.emory.edu/PROGRAMS/autism/pdd.html#7. Last accessed December 5, 2013.
67. National Institute of Neurological Disorders and Stroke. Rett Syndrome Information Page. Available at http://www.ninds.nih.gov/disorders/rett/detail_rett.htm. Last accessed December 2, 2013.
68. National Institute of Neurological Disorders and Stroke. Landau-Kleffner Syndrome Information Page. Available at http://www.ninds.nih.gov/disorders/landaukleffnersyndrome/landaukleffnersyndrome.htm. Last accessed December 2, 2013.
69. Nation K, Penny S. Sensitivity to eye gaze in autism: is it normal? Is it automatic? Is it social? Dev Psychopathol. 2008;20(1):79-97.
70. Senju A, Kikuchi Y, Hasegawa T, Tojo Y, Osanai H. Is anyone looking at me? Direct gaze detection in children with and without autism. Brain Cogn. 2008;67(2):127-139.
71. Rapin I, Dunn M. Update on the language disorders of individuals on the autistic spectrum. Brain Dev. 2003;25(3):166-172.
72. McCann J, Peppe S, Gibbon FE, O'Hare A, Rutherford M. Prosody and its relationship to language in school-aged children with high-functioning autism. Int J Lang Commun Disord. 2007;42(6):682-702.
73. Diehl JJ, Bennetto L, Watson D, Gunlogson C, McDonough J. Resolving ambiguity: a psycholinguistic approach to understanding prosody processing in high-functioning autism. Brain Lang. 2008;106(2):144-152.
75. Gerhardt PF. The Current State of Services for Adults with Autism. Available at http://inresco.org/as/thinktankf/oar_survey_11309.pdf. Last accessed December 5, 2013.
76. Wiggins LD, Baio J, Rice C. Examination of the time between first evaluation and first autism spectrum diagnosis in a population-based sample. J Dev Behav Pediatr. 2006;27(2 Suppl):S79-S87.
77. Buescher AVS, Cidav Z, Knapp M, Mandell DS. Costs of autism spectrum disorders in the United Kingdom and the United States. JAMA Pediatr. 2014;168(8):721-728.
78. Ozonoff S, Young GS, Carter A, et al. Recurrence risk for autism spectrum disorders: a Baby Siblings Research Consortium study. Pediatrics. 2011;128(3):e488-495.
79. Shulman L. DSM-5 and the New Autism Spectrum Disorder Criteria: What's It All About? Available at http://www.einstein.yu.edu/uploadedfiles/Centers/childrens-evaluation-rehabilitation/eiti-summer-2013.pdf. Last accessed November 7, 2013.
80. King BH, Hollander E, Sikich L, et al. Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior: citalopram ineffective in children with autism. Arch Gen Psychiatry. 2009;66(6):583-590.
81. Williams K, Wheeler DM, Silove N, Hazell P. Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD). Cochrane Database Syst Rev. 2010;(8):CD004677.
82. Deonna T, Roulet-Perez E. Early-onset acquired epileptic asphasia (Landau-Kleffner syndrome, LKS) and regressive autistic disorders with epileptic EEG abnormalities: the continuing debate. Brain Dev. 2010;32(9):746-752.
83. Neiman ES, Seyffert M. Landau-Kleffner Syndrome. Available at http://emedicine.medscape.com/article/1176568-overview. Last accessed December 4, 2013.
85. Duran MH, Guimaraes CA, Medeiros LL, Guerreiro MM. Landau-Kleffner syndrome: long-term follow-up. Brain Dev. 2009;31(1):58-63.
87. Homan KJ, Mellon MW, Houlihan D, Katusic MZ. Brief report: childhood disintegrative disorder: a brief examination of eight case studies. J Autism Dev Disord. 2011;41(4):497-504.
88. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington, DC: American Psychiatric Association; 2013.
89. American Psychiatric Association. Autism Spectrum Disorder Fact Sheet. Available at http://www.dsm5.org/Documents/Autism%20Spectrum%20Disorder%20Fact%20Sheet.pdf. Last accessed December 3, 2013.
91. McConkie-Rosell A, Finucane B, Cronister A, Abrams L, Bennett RL, Pettersen BJ. Genetic counseling for fragile X syndrome: updated recommendations of the National Society of Genetic Counselors. J Genet Counsel. 2005;14(4):249-270.
92. Stachnik JM, Nunn-Thompson C. Use of atypical antipsychotics in the treatment of autistic disorder. Ann Pharmacother. 2007;41(4):626-634.
93. Nickels K, Katusic SK, Colligan RC, Weaver AL, Voigt RG, Barbaresi WJ. Stimulant medication treatment of target behaviors in children with autism: a population-based study. J Dev Behav Pediatr. 2008;29(2):75-81.
94. Correll CU, Manu P, Olshanskiy V, Napolitano B, Kane JM, Malhotra AK. Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA. 2009;302(16):1765-1773.
95. Malone RP, Waheed A. The role of antipsychotics in the management of behavioural symptoms in children and adolescents with autism. Drugs. 2009;69(5):535-548.
96. Swinson RP, Antony MM, Rachman S, Richter MA (eds). Obsessive-Compulsive Disorder Theory, Research, and Treatment. New York, NY: The Guilford Press; 1998.
97. National Institute of Mental Health. Autism Spectrum Disorder. Available at http://www.nimh.nih.gov/health/topics/autism-spectrum-disorders-pervasive-developmental-disorders/index.shtml. Last accessed December 3, 2013.
98. LexiComp Online. Available at http://online.lexi.com. Last accessed December 3, 2013.
99. U.S. Food and Drug Administration. FDA Approves the First Drug to Treat Irritability Associated with Autism, Risperdal. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2006/ucm108759.htm. Last accessed December 3, 2013.
100. Jesner OS, Aref-Adib M, Coren E. Risperidone for autism spectrum disorder. Cochrane Database Syst Rev. 2007;(1):CD005040.
101. McCracken JT, McGough J, Shah B, et al. Risperidone in children with autism and serious behavioral problems. N Engl J Med. 2002;347:314-321.
102. Malone RP, Cater J, Sheikh RM, Choudhury MS, Delaney MA. Olanzapine versus haloperidol in children with autistic disorder: an open pilot study. J Am Acad Child Adolesc Psychiatry. 2001;40(8):887-894.
103. Barnard L, Young AH, Pearson J, Geddes J, O'Brien G. A systematic review of the use of atypical antipsychotics in autism.JPsychopharmacol. 2002;16(1):93-101.
104. McDougle CJ, Kem DL, Posey DJ. Case series: use of ziprasidone for maladaptive symptoms in youths with autism. J Am Acad Child Adolesc Psychiatry. 2002;41(8):921-927.
105. Posey DJ, Aman MG, McCracken JT, et al. Positive effects of methylphenidate on inattention and hyperactivity in pervasive developmental disorders: an analysis of secondary measures. Biol Psychiatry. 2007;61(4):538-544.
106. National Institutes of Health. The Use of Secretin to Treat Autism. Available at http://www.nichd.nih.gov/news/releases/pages/secretin.aspx. Last accessed December 3, 2013.
107. Williams KJ, Wray JJ, Wheeler DM. Intravenous secretin for autism spectrum disorder. Cochrane Database Syst Rev. 2005;(3):CD003495.
108. Autism Society. Summary of Biomedical Treatments for Autism. Available at http://www.autism-society.org/living-with-autism/treatment-options/summary-of-biomedical.html. Last accessed December 4, 2013.
109. National Autism Resources. Picture Exchange Communication System (PECS). Available at http://www.nationalautismresources.com/picture-exchange-communication-system.html. Last accessed December 4, 2013.
110. Nye C, Brice A. Combined vitamin B6-magnesium treatment in autism spectrum disorder. Cochrane Database Syst Rev. 2005;19(4):CD003497.
111. Hjiej H, Doyen C, Couprie C, Kaye K, Contejean Y. Substitutive and dietetic approaches in childhood autistic disorder: Interests and limits. Encephale. 2008;34(5):496-503.
112. Millward C, Ferriter M, Calver S, Connell-Jones G. Gluten- and casein-free diets for autistic spectrum disorder. Cochrane Database Syst Rev. 2008;16(2):CD003498.
113. American College of Allergy, Asthma, and Immunology. Food allergy: a practice parameter. Ann Allergy Asthma Immunol. 2006;96(3 suppl 2):S1-S68.
114. Levy SE, Hyman SL. Novel treatments for autistic spectrum disorders. Ment Retard Dev Disabil Res Rev. 2005;11(2):131-142.
116. Interactive Autism Network (IAN) Community. Social Skills Interventions: Getting to the Core of Autism. Available athttp://www.iancommunity.org/cs/what_do_we_know/social_skills_interventions. Last accessed December 5, 2013.
118. The National Autistic Society. Picture Exchange Communication System. Available at http://www.autism.org.uk/living-with-autism/strategies-and-approaches/alternative-and-augmentative-communication/picture-exchange-communication-system.aspx. Last accessed December 5, 2013.
119. Schwartz IS, Garfinkle AN, Bauer J. The picture exchange communication system: communicative outcomes for young children with disabilities. Top Early Child Special Education. 1998;18(3):144-159.
120. Autism Treatment Services of Canada. Occupational Therapy and Autistic Children. Available at http://autism.ca/occther.htm. Last accessed December 5, 2013.
121. Interactive Autism Network Community. IAN Research Findings: Occupational Therapy. Available at http://www.iancommunity.org/cs/ian_treatment_reports/occupational_therapy. Last accessed December 5, 2013.
122. Helpguide.org. Autism Help Guide. Available at http://www.helpguide.org/topics/autism.htm. Last accessed December 5, 2013.
123. AutismSpeaks.org. Treatments and Therapies: Sensory Integration (SI). Available at http://www.autismspeaks.org/family-services/tool-kits/100-day-kit/treatments-therapies. Last accessed December 5, 2013.
124. Josefi O, Ryan V. Non-directive play for young children with autism: a case study. Clin Child Psychol Psychiatry. 2004;9(4):533-551.
125. Holmes AS. Early Intervention Can Make a Difference. Available at http://www.autism-society.org/living-with-autism/lifespan/infants-toddlers/early-intervention.pdf. Last accessed December 5, 2013.
126. Autism Society. Educational Planning. Available at http://www.autism-society.org/living-with-autism/lifespan/school-age/educational-planning.html. Last accessed December 5, 2013.
127. Buckman S, Indiana Resource Center for Autism. Critical Features of Early Intervention: Merging Best Practices. Available at http://www.iidc.indiana.edu/index.php?pageId=442. Last accessed December 5, 2013.
128. British Columbia Ministry of Education: Special Programs Branch. Teaching Students with Autism: A Resource Guide for Schools. Available at http://www.bced.gov.bc.ca/specialed/docs/autism.pdf. Last accessed December 5, 2013.
129. National Institute on Deafness and Other Communication Disorders. Communication Problems in Children with Autism. Available at http://www.nidcd.nih.gov/staticresources/health/voice/CommunicationProblemsInChildrenWithAutism.pdf. Last accessed December 5, 2013.
130. The Kansas Center for Autism Research and Training. School-Age Services. Available at http://www.kcart.ku.edu/families/school_services.shtml. Last accessed December 5, 2013.
131. Committee on Educational Interventions for Children with Autism, Lord C, McGee J (eds). Educating Children with Autism. Washington, DC: National Academies Press; 2001.
132. Harris SL, Handleman JS. Age and IQ at intake as predictors of placement for young children with autism: a four-to-six-year follow-up. J Autism Dev Disord. 2000;30(2):137-142.
133. Vicker B, Indiana Resource Center for Autism. Aiding Comprehension of Individuals with Autism Spectrum Disorders during One-on-One Interactions. Available at http://www.iidc.indiana.edu/index.php?pageId=538. Last accessed December 5, 2013.
134. Goldstein H. Communication intervention for children with autism: a review of treatment efficacy. J Autism Dev Disord. 2002;32(5):373-396.
135. Fernandez BA, Roberts W, Chung B, et al. Phenotypic spectrum associated with de novo and inherited deletions and duplications at 16p11.2 in individuals ascertained for diagnosis of autism spectrum disorder. J Med Genet. 2010;47:195-203.
1. Filipek PA, Accardo PJ, Ashwal S, et al. Practice parameter: screening and diagnosis of autism: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Child Neurology Society. Neurology. 2000;55(4):468-479. Summary retrieved from National Guideline Clearinghouse at http://www.guideline.gov/content.aspx?id=2822. Last accessed December 12, 2013.
2. Scottish Intercollegiate Guidelines Network. Assessment, Diagnosis and Clinical Interventions for Children and Young People with Autism Spectrum Disorders: A National Clinical Guideline. Edinburgh: Scottish Intercollegiate Guidelines Network; 2007. Summary retrieved from National Guideline Clearinghouse at http://www.guideline.gov/content.aspx?id=11011. Last accessed December 12, 2013.
Mention of commercial products does not indicate endorsement.