Autism spectrum

Classification

In the United States, a revision to autism spectrum disorder (ASD) was presented 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. Compared with the DSM-IV diagnosis of autistic disorder, the DSM-5 diagnosis of ASD no longer includes communication as a separate criterion, and has merged social interaction and communication into one category. Slightly different diagnostic definitions are used in other countries. For example, the ICD-10 is the most commonly-used diagnostic manual in the UK.

Rather than categorizing these diagnoses, the DSM-5 has adopted a dimensional approach to diagnosing disorders that fall underneath the autism spectrum umbrella. Some have proposed that individuals on the autism spectrum may be better represented as a single diagnostic category. Within this category, the DSM-5 has proposed a framework of differentiating each individual by dimensions of severity, as well as associated features (i.e., known genetic disorders, and intellectual disability).

Another 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 restricting 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. Asperger syndrome is closest to autism in signs and likely causes; unlike autism, people with Asperger syndrome have no significant delay in language development, according to the older DSM-4 criteria. 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.

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 earlier was intended to describe a specific set of diagnostic labels, whereas the latter refers to a postulated spectrum disorder linking various conditions. ASD 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 the DSM-5, autism is characterized by persistent deficits in social communication and interaction across multiple contexts, as well as restricted, repetitive patterns of behavior, interests, or activities. These deficits are present in early childhood, and lead to clinically significant functional impairment. There is also a unique form of autism called autistic savantism, where a child can display outstanding skills in music, art, and numbers with no practice. Because of its relevance to different populations, self-Injurious behaviors (SIB) are not considered a core characteristic of the ASD population however approximately 50% of those with ASD take part in some type of SIB (head-banging, self-biting) and are more at risk than other groups with developmental disabilities.

Some of the language behaviors typically seen in children with autism may include repetitive or rigid language, specific interests in conversation, atypical language development, or poor nonverbal communication skills, including lack of eye contact and meaningful gestures and facial expressions.

Asperger syndrome was distinguished from autism in the DSM-IV by the lack of delay or deviance in early language development. Additionally, individuals diagnosed 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 DSM-5 eliminated the four separate diagnosis: Asperger Syndrome, Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS), Childhood Degenerative Disorder, and Autistic Disorder and combined them under the diagnosis of Autism Spectrum Disorder.

Developmental course

Autism spectrum disorders are thought to follow two possible developmental courses, although most parents report that symptom onset occurred within the first year of life. One course of development is more gradual in nature, 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. While there is conflicting evidence surrounding language outcomes in ASD, some studies have shown that cognitive and language abilities at age  2 ¹⁄₂ may help predict language proficiency and production after age 5. Overall, the literature stresses the importance of early intervention in achieving positive longitudinal outcomes.

Causes

While specific causes of autism spectrum disorders have yet to be found, many risk factors have been identified in the research literature that may contribute to their development. 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 components of the autism spectrum disorders.

Prenatal and perinatal risk factors

Several 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.

Low vitamin D levels in early development has been hypothesized as a risk factor for autism.

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, and further evidence continues to refute them, including the observation that the rate of autism continues to climb despite elimination of thimerosal from routine childhood vaccines. A 2014 meta-analysis examined ten major studies on autism and vaccines involving 1.25 million children worldwide; it concluded that neither the MMR vaccine, which has never contained thimerosal, nor the vaccine components thimerosal or mercury, lead to the development of ASDs.

Pathophysiology

In general, neuroanatomical studies support the concept that autism may involve a combination of brain enlargement in some areas and reduction in others. 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 somatosensory cortices of the brain than the median member of a properly sampled control population. This finding coincides with reports demonstrating 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. 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 suggested that ASD could be linked to mitochondrial disease (MD), a basic cellular abnormality with 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 MD. It is unclear why the MD occurs considering that only 23% of children with both ASD and MD present with mitochondrial DNA (mtDNA) abnormalities.

Serotonin

It has been hypothesized that increased activity of serotonin in the developing brain may facilitate the onset of autism spectrum disorder, with an association found in six out of eight studies between the use of selective serotonin reuptake inhibitors (SSRIs) by the pregnant mother and the development of ASD by the child exposed to SSRI in the antenatal environment. The study could not definitively conclude SSRIs caused the increased risk for ASDs due to the biases found in those studies, and the authors called for more definitive, better conducted studies.

Evidence-based assessment

ASD can be detected as early as eighteen months or even younger in some cases. A reliable diagnosis can usually be made by the age of two. 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 must differentiate among the different pervasive developmental disorders, and may also consider similar conditions, including intellectual disability not associated with a pervasive developmental disorder, specific language disorders, ADHD, anxiety, and psychotic disorders.

Considering the unique challenges in diagnosing ASD, specific practice parameters for its assessment 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 shows initial evidence of ASD tendencies, psychologists administer various psychological assessment tools to assess for ASD. Among 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 several opportunities (or "presses") for spontaneous behaviors (e.g., eye contact) in standardized context. Various other questionnaires (e.g., The Childhood Autism Rating Scale, Autism Treatment Evaluation Checklist) and tests of cognitive functioning (e.g., The Peabody Picture Vocabulary Test) are typically included in an ASD assessment battery.

In the UK, there is some diagnostic use of the Diagnostic Interview for Social and Communication Disorders (DISCO) was which was developed for use at The Centre for Social and Communication Disorders, by Lorna Wing and Judith Gould, as both a clinical and a research instrument for use with children and adults of any age. The DISCO is designed to elicit a picture of the whole person through the story of their development and behaviour. In clinical work, the primary purpose is to facilitate understanding of the pattern over time of the specific skills and impairments that underlie the overt behaviour. If no information is available, the clinician has to obtain as much information as possible concerning the details of current skills and pattern of behaviour of the person. This type of dimensional approach to clinical description is useful for prescribing treatment.

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 an intellectual disability, with females more likely to be in the severe range of an intellectual disability. A number of genetic syndromes causing intellectual disability may also be comorbid with ASD, including fragile X syndrome, Down syndrome, Prader-Willi and Angelman syndromes, and Williams syndrome.

Learning disabilities are also highly comorbid in individuals with an ASD. Approximately 25-75% of individuals with an ASD also have some degree of a learning disability.

Various 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%. The relationship between ASD and schizophrenia remains a controversial subject under continued investigation, and recent meta-analyses have examined genetic, environmental, infectious, and immune risk factors that may be shared between the two conditions.

Deficits in ASD are often linked to behavior problems, such as difficulties following directions, being cooperative, and doing things on other people's terms. Symptoms similar to those of attention deficit hyperactivity disorder (ADHD) can be part of an ASD diagnosis.

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

Management

There is no known cure for autism, although those with Asperger syndrome and those who have autism and require little-to-no support are more likely to experience a lessening of symptoms over time. The main goals of treatment are to lessen associated deficits and family distress, and to increase quality of life and functional independence. In general, higher IQs are correlated with greater responsiveness to treatment and improved treatment outcomes. Although evidence-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.

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, developmental models, structured teaching, speech and language therapy, social skills therapy, and occupational therapy. Among these approaches, interventions either treat autistic features comprehensively, or focus treatment on a specific area of deficit.

There has been increasing attention to the development of evidence-based interventions for young children with ASD. Two theoretical frameworks outlined for early childhood intervention include applied behavioral analysis (ABA) and the developmental social-pragmatic model (DSP). Although ABA therapy has a strong evidence base, particularly in regard to early intensive home-based therapy. ABA's effectiveness may be limited by diagnostic severity and IQ of the person effected by ASD. The Journal of Clinical Child and Adolescent Psychology has deemed two early childhood interventions as “well-established”: individual comprehensive ABA, and focused teacher-implemented ABA combined with DSP.

Another evidence-based intervention that has demonstrated efficacy is a parent training model, which teaches parents how to implement various ABA and DSP techniques themselves. Various DSP programs have been developed to explicitly deliver intervention systems through at-home parent implementation.

A multitude of unresearched alternative therapies have also been implemented. Many have resulted in harm to autistic people and should not employed unless proven to be safe.

In October 2015, the American Academy of Pediatrics (AAP) proposed new evidence-based recommendations for early interventions in ASD for children under 3. These recommendations emphasize early involvement with both developmental and behavioral methods, support by and for parents and caregivers, and a focus on both the core and associated symptoms of ASD.

Epidemiology

The U.S. Center for Disease Control's most recent estimate is that 1 out of every 68 children, or 14.7 per 1,000, have some form of ASD as of 2010. Reviews tend to estimate a prevalence of 6 per 1,000 for autism spectrum disorders as a whole, although 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 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 intellectual disability, the sex ratio may be closer to 2:1. Prevalence differences may be a result of gender differences in expression of clinical symptoms, with autistic 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. The "refrigerator mother" theory has since continued to be refuted in scientific literature, including a 2015 systematic review which showed no association between caregiver interaction and language outcomes in ASD.

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.

Caregivers

Families who care for an autistic child face added stress from a number of different causes. Parents may be shocked and dismayed by the diagnosis, and they may struggle to understand their child's diagnosis and find appropriate care options. They also struggle emotionally. In the words of a physician whose two children were both diagnosed with autism, “In the moment of diagnosis, it feels like the death of your hopes and dreams.”

One study found that half of parents who had a child with any kind of developmental disability were still caring for their child by age 50, while only 17% of parents that age would typically be caring for children.

Autism rights movement

The autism rights movement (ARM) is a social movement within the neurodiversity movement that encourages autistic people, their caregivers, and society to adopt a position of neurodiversity, and to accept autism as a variation in functioning rather than a mental disorder to be cured. The ARM advocates for several goals, including a greater acceptance of autistic behaviors, therapies that teach autistic individuals coping skills rather than therapies focused on imitating behaviors of neurotypical peers, the creation of social networks and events that allow autistic people to socialize on their own terms, and the recognition of the autistic community as a minority group.

Autism rights and neurodiversity advocates believe that the autism spectrum is genetic and should be accepted as a natural expression of the human genome. This perspective is distinct from two other likewise distinct views:

The movement is controversial. A common criticism leveled against autistic activists is that many have Asperger syndrome or are otherwise high-functioning, and therefore do not represent the views of all autistic people.