Autism spectrum disorder

The autism spectrum or autistic spectrum describes a range of conditions classified as neurodevelopmental disorders in the fifth revision of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5). The DSM-5, published in 2013, redefined the autism spectrum to encompass the previous (DSM-IV-TR) diagnoses of autism, Asperger syndrome, pervasive developmental disorder not otherwise specified (PDD-NOS), childhood disintegrative disorder, and Rett syndrome. These disorders are characterized by social deficits and communication difficulties, stereotyped or repetitive behaviors and interests, and in some cases, cognitive delays.

Classification
A revision to autism spectrum disorder was proposed in the Diagnostic and Statistical Manual of Mental Disorders version 5 (DSM-5), released May 2013. The new diagnosis encompasses previous diagnoses of autistic disorder, Asperger's disorder, childhood disintegrative disorder, and PDD-NOS. Rather than categorizing these diagnoses, the DSM-5 will adopt a dimensional approach to diagnosing disorders that fall underneath the autism spectrum umbrella. It is thought that individuals with ASDs are best represented as a single diagnostic category because they demonstrate similar types of symptoms and are better differentiated by clinical specifiers (i.e., dimensions of severity) and associated features (i.e., known genetic disorders, epilepsy and intellectual disability). An additional change to the DSM includes collapsing social and communication deficits into one domain. Thus, an individual with an ASD diagnosis will be described in terms of severity of social communication symptoms, severity of fixated or restricted behaviors or interests and associated features. The restriction of onset age has also been loosened from 3 years of age to "early developmental period", with a note that symptoms may manifest later when demands exceed capabilities.

Autism forms the core of the autism spectrum disorders (ASD). Asperger syndrome is closest to autism in signs and likely causes; unlike autism, people with Asperger syndrome have no significant delay in language development. PDD-NOS is diagnosed when the criteria are not met for a more specific disorder. Some sources also include Rett syndrome and childhood disintegrative disorder, which share several signs with autism but may have unrelated causes; other sources differentiate them from ASD, but group all of the above conditions into the pervasive developmental disorders.

The terminology of autism can be bewildering. Autism, Asperger syndrome, and PDD-NOS are sometimes called the autistic disorders instead of ASD, whereas autism itself is often called autistic disorder, childhood autism, or infantile autism. Although the older term pervasive developmental disorder and the newer term autism spectrum disorder largely or entirely overlap, the former was intended to describe a specific set of diagnostic labels, whereas the latter refers to a postulated spectrum disorder linking various conditions. ASD, in turn, is a subset of the broader autism phenotype (BAP), which describes individuals who may not have ASD but do have autistic-like traits, such as avoiding eye contact.

Characteristics
Under DSM-IV-TR, autism was characterized by delays or abnormal functioning before the age of three years in one or more of the following domains: (1) social interaction; (2) communication; and (3) restricted, repetitive, and stereotyped patterns of behavior, interests, and activities.

Asperger syndrome was distinguished from autism by the lack of delay or deviance in early language development. Additionally, individuals with Asperger syndrome did not have significant cognitive delays.

PDD-NOS was considered "subthreshold autism" and "atypical autism" because it was often characterized by milder symptoms of autism or symptoms in only one domain (such as social difficulties).

The theory of monotropism proposes that children on the Autism Spectrum have difficulty shifting their attention out of the individual's attention tunnel.

Developmental course
Although autism spectrum disorders are thought to follow two possible developmental courses, most parents report that symptom onset occurred within the first year of life. One course of development follows a gradual course of onset in which parents report concerns in development over the first two years of life and diagnosis is made around 3–4 years of age. Some of the early signs of ASDs in this course include decreased looking at faces, failure to turn when name is called, failure to show interests by showing or pointing, and delayed pretend play. A second course of development is characterized by normal or near-normal development followed by loss of skills or regression in the first 2–3 years. Regression may occur in a variety of domains, including communication, social, cognitive, and self-help skills; however, the most common regression is loss of language. There continues to be a debate over the differential outcomes based on these two developmental courses. Some studies suggest that regression is associated with poorer outcomes and others report no differences between those with early gradual onset and those who experience a regression period. Overall, the prognosis is poor for persons with classical (Kanner-type) autism with respect to academic achievement and poor to below-average for persons across the autism spectrum with respect to independent living abilities; in each case, a lack of early intervention exacerbates the odds against success. However, many individuals show improvements as they grow older. The two best predictors of favorable outcome in autism are the absence of intellectual disability and the development of some communicative speech prior to five years of age. Overall, the literature stresses the importance of early intervention in achieving positive longitudinal outcomes.

Causes
While a specific cause or specific causes of autism spectrum disorders has yet to be found, many risk factors have been identified in the research literature that may contribute to the development of an ASD. These risk factors include genetics, prenatal and perinatal factors, neuroanatomical abnormalities, and environmental factors.

It is possible to identify general risk factors, but much more difficult to pinpoint specific factors. In the current state of knowledge, prediction can only be of a global nature and therefore requires the use of general markers.

Genetic risk factors
The results of family and twin studies suggest that genetic factors play a role in the etiology of autism and other pervasive developmental disorders. Studies have consistently found that the prevalence of autism in siblings of autistic children is approximately 15 to 30 times greater than the rate in the general population. In addition, research suggests that there is a much higher concordance rate among monozygotic twins compared to dizygotic twins. It appears that there is no single gene that can account for autism. Instead, there seem to be multiple genes involved, each of which is a risk factor for part of the autism syndrome through various groups.

Associated conditions

 * Intellectual disability
 * Seizures and epilepsy
 * Tuberous sclerosis
 * Fragile X syndrome
 * Chromosome 15q11-q13 interstal duplication, du/triplications
 * Chromosome 15q11-q13 deletions (i.e. Angelman syndrome and Prader-Willi syndrome)
 * Rett syndrome
 * Smith-Lemli-Opitz syndrome, a cholesterol biosynthesis disorder

Prenatal and perinatal risk factors
A number of prenatal and perinatal complications have been reported as possible risk factors for autism. These risk factors include maternal gestational diabetes, maternal and paternal age over 30, bleeding after first trimester, use of prescription medication (e.g. valproate) during pregnancy, and meconium in the amniotic fluid. While research is not conclusive on the relation of these factors to autism, each of these factors has been identified more frequently in autistic children compared to their non-autistic siblings and other normally developing youth.

Vaccine controversy
Perhaps the most controversial claim regarding autism etiology was the "vaccine controversy". This conjecture, arising from a case of scientific misconduct, suggested that autism results from brain damage caused either by (1) the measles, mumps, rubella (MMR) vaccine itself, or by (2) thimerosal, a vaccine preservative. No convincing scientific evidence supports these claims, based on various lines of evidence including the observation that the rate of autism continues to climb despite elimination of thimerosal from routine childhood vaccines.

Pathophysiology
In general, neuroanatomical studies support the notion that autism is linked to a combination of brain enlargement in some areas and brain reduction in other areas. These studies suggest that autism may be caused by abnormal neuronal growth and pruning during the early stages of prenatal and postnatal brain development, leaving some areas of the brain with too many neurons and other areas with too few neurons. Some research has reported an overall brain enlargement in autism while others suggest abnormalities in several areas of the brain, including the frontal lobe, the mirror neuron system, the limbic system, the temporal lobe, and the corpus callosum.

In neuroanatomical studies, when performing Theory of Mind and facial emotion response tasks, the median person on the autism spectrum exhibits less activation in the primary and secondary somato-sensory cortices than does the median member of a properly sampled control population. This discrepancy is consistent with reports of abnormal patterns of cortical thickness and grey matter volume in those regions of autistic persons' brains.

Mirror neuron system
The mirror neuron system (MNS) consists of a network of brain areas that have been associated with empathy processes in humans. In humans, the MNS has been identified in the inferior frontal gyrus (IFG) and the inferior parietal lobule (IPL) and is thought to be activated during imitation or observation of behaviors. It has been proposed that problems with the mirror neuron system may underlie autism;  however the connection between mirror neuron dysfunction and autism is tentative and it remains to be seen how mirror neurons may be related to many of the important characteristics of autism.

Temporal lobe
Functions of the temporal lobe are related to many of the deficits observed in individuals with ASDs, such as receptive language, social cognition, joint attention, action observation, and empathy. The temporal lobe also contains the superior temporal sulcus (STS) and the fusiform face area (FFA), which may mediate facial processing. It has been argued that dysfunction in the STS underlies the social deficits that characterize autism. Compared to typically developing individuals, one fMRI study found that individuals with high-functioning autism had reduced activity in the FFA when viewing pictures of faces.

Mitochondrial dysfunction
It has been noted that children with ASD are afflicted with undiagnosed comorbid conditions such as abnormalities in the peripheral nervous, immune, gastrointestinal and energy production systems, suggesting that ASD isn't strictly a central nervous system (CNS) disorder, but rather a systemic one. It has been hypothesized that ASD could be linked to a mitochondrial disorder, as it is a basic cellular abnormality that has the potential to cause disturbances in a wide range of body systems. A recent meta-analysis study, as well as other population studies have shown that approximately 5% of children with ASD meet the criteria for classical mitochondrial disease (MD), and that around 7.2 to 80 percent of children with ASD present with some variant of mitochondrial dysfunction. It is currently unclear why the mitochondrial dysfunction occurs considering that only 23% of children with both ASD and MD present with mitochondrial DNA (mtDNA) abnormalities.

Evidence-based assessment
The diverse expressions of ASD symptoms pose diagnostic challenges to clinicians. Individuals with an ASD may present at various times of development (e.g., toddler, child, or adolescent) and symptom expression may vary over the course of development. Furthermore, clinicians are required to differentiate among the different pervasive developmental disorders as well as other disorders such as mental retardation not associated with a pervasive developmental disorder, specific developmental disorders (e.g. language), and early onset schizophrenia, as well as the social-cognitive deficits caused by brain damage from alcohol abuse.

Considering the unique challenges associated with diagnosing ASD, specific practice parameters for the assessment of ASD have been published by the American Academy of Neurology, the American Academy of Child and Adolescent Psychiatry, and a consensus panel with representation from various professional societies. The practice parameters outlined by these societies include an initial screening of children by general practitioners (i.e., "Level 1 screening") and for children who fail the initial screening, a comprehensive diagnostic assessment by experienced clinicians (i.e. "Level 2 evaluation"). Furthermore, it has been suggested that assessments of children with suspected ASD be evaluated within a developmental framework, include multiple informants (e.g., parents and teachers) from diverse contexts (e.g., home and school), and employ a multidisciplinary team of professionals (e.g., clinical psychologists, neuropsychologists, and psychiatrists).

After a child fails an initial screening, psychologists administer various psychological assessment tools to assess for ASD. Amongst these measurements, the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) are considered the "gold standards" for assessing autistic children. The ADI-R is a semi-structured parent interview that probes for symptoms of autism by evaluating a child's current behavior and developmental history. The ADOS is a semistructured interactive evaluation of ASD symptoms that is used to measure social and communication abilities by eliciting a number of opportunities (or "presses") for spontaneous behaviors (e.g., eye contact) in standardized context. Various other questionnaires (e.g., The Childhood Autism Rating Scale) and tests of cognitive functioning (e.g., The Peabody Picture Vocabulary Test) are typically included in an ASD assessment battery.

Comorbidity
Autism spectrum disorders tend to be highly comorbid with other disorders. Comorbidity may increase with age and may worsen the course of youth with ASDs and make intervention/treatment more difficult. Distinguishing between ASDs and other diagnoses can be challenging because the traits of ASDs often overlap with symptoms of other disorders and the characteristics of ASDs make traditional diagnostic procedures difficult.

The most common medical condition occurring in individuals with autism spectrum disorders is seizure disorder or epilepsy, which occurs in 11-39% of individuals with ASD. Tuberous sclerosis, a medical condition in which non-malignant tumors grow in the brain and on other vital organs, occurs in 1-4% of individuals with ASDs.

Intellectual disabilities are some of the most common comorbid disorders with ASDs. Recent estimates suggest that 40-69% of individuals with ASD have some degree of mental retardation, with females more likely to be in severe range of mental retardation. Learning disabilities are also highly comorbid in individuals with an ASD. Approximately 25-75% of individuals with an ASD also have some degree of learning disability.

A variety of anxiety disorders tend to co-occur with autism spectrum disorders, with overall comorbidity rates of 7-84%. Rates of comorbid depression in individuals with an ASD range from 4–58%.

Deficits in ASD are often linked to behavior problems, such as difficulties following directions, being cooperative, and doing things on other people's terms. Attention Deficit Hyperactivity Disorder (ADHD)-like symptoms are seen to be part of the ASD diagnosis.

Sensory processing disorder is also comorbid with ASD, with comorbidity rates of 42-88%.

Management
The main goals of treatment are to lessen associated deficits and family distress, and to increase quality of life and functional independence. No single treatment is best and treatment is typically tailored to the child's needs. Intensive, sustained special education programs and behavior therapy early in life can help children acquire self-care, social, and job skills. Available approaches include applied behavior analysis (ABA), developmental models, structured teaching, speech and language therapy, social skills therapy, and occupational therapy. There has been increasing attention to the development of evidenced-based interventions for young children with ASDs. Unresearched alternative therapies have also been implemented (for example, vitamin therapy and acupuncture). Although evidenced-based interventions for autistic children vary in their methods, many adopt a psychoeducational approach to enhancing cognitive, communication and social skills while minimizing problem behaviors. It has been argued that no single treatment is best and treatment is typically tailored to the child's needs.

One of the most empirically supported intervention approaches is applied behavioral analysis, particularly in regard to early intensive home-based therapy. Although ABA therapy has a strong research base, other studies have found that this approach may be limited by diagnostic severity and IQ.

Early Intensive Behavioral Intervention (EIBI), through the use of Applied Behavioral Analysis (ABA), has been researched for over 40 years in its effectiveness. Most EIBI programs recognize that all skills appropriate for each specific age are teachable and should be taught. General curriculum areas that are addressed are language, social skills, play skills, motor skills, pre-academic and academic skills, and independent living skills. ABA models of intervention for preschool age include two main approaches to teaching. "Discrete Trial Teaching" or DTT, includes multiple discrete opportunities that are presented across the day or session. A discrete trial consists of the therapist presenting an instruction, the child responding, and the therapist responding to that by presenting a consequence. If the child responds incorrectly, the reinforcer is not given and the therapist will follow up with an error correction procedure, followed by another trial. A strength of this way of teaching is the child receives a large number of trials in a short time, allowing for a large amount of learning opportunities. A potential weakness may be that the skills learned in this structured setting are not easily generalized in less strict settings. "Natural Environment Teaching" consists of maximizing naturally occurring learning opportunities. It involves a more child-directed format that allows for the child to initiate learning, and the therapist to recognize this and follow it by prompting the child for a desired behavior before giving the reinforcer.

Epidemiology
Reviews tend to estimate a prevalence of 6 per 1,000 for autism spectrum disorders as a whole, however prevalence rates vary for each of the developmental disorders in the spectrum. Autism prevalence has been estimated at 1-2 per 1,000, Asperger syndrome at roughly 0.6 per 1,000, childhood disintegrative disorder at 0.02 per 1,000, and PDD-NOS at 3.7 per 1,000. These rates are consistent across cultures and ethnic groups, as autism is considered a universal disorder.

While rates of autism spectrum disorders are consistent across cultures, they vary greatly by gender, with boys being affected far more frequently than girls. The average male-to-female ratio for ASDs is 4.2:1, affecting 1 in 70 males, but only 1 in 315 females. Females, however, are more likely to have associated cognitive impairment. Among those with an ASD and mental retardation, the sex ratio may be closer to 2:1. Prevalence differences might be accounted by gender differences in the expression of clinical symptoms, with females showing less atypical behaviors and, therefore, less likely to receive an ASD diagnosis.

History
Controversies have surrounded various claims regarding the etiology of autism spectrum disorders. In the 1950s, the "refrigerator mother theory" emerged as an explanation for autism. The hypothesis was based on the idea that autistic behaviors stem from the emotional frigidity, lack of warmth, and cold, distant, rejecting demeanor of a child's mother. Naturally, parents of children with an autism spectrum disorder suffered from blame, guilt, and self-doubt, especially as the theory was embraced by the medical establishment and went largely unchallenged into the mid-1960s. While the "refrigerator mother theory" has been rejected in the research literature, its effects have lingered into the 21st century. Another controversial claim suggests that watching extensive amounts of television may cause autism. This hypothesis was largely based on research suggesting that the increasing rates of autism in the 1970s and 1980s were linked to the growth of cable television at this time. This conjecture has not been supported in the research literature.