Autism Spectrum Disorder

Patricia Howlin (UK)

Abstract

In recent years there have been many improvements in our knowledge and understanding of autism spectrum disorder (ASD). The following article provides an update on prevalence data, theories of causation, and recent changes to diagnostic classification systems. Assessment instruments that can be used to identify individuals at risk of ASD and/or to assist in the diagnostic process are discussed. Evidence for the effectiveness of many intervention programmes remains limited although interventions with a focus on early parent-child relationships have a growing evidence base. The generally poor outcome for adults with ASD, including those of average or above intellectual ability is highlighted and possible ways of improving outcome in the future are considered.

Key words

Autism; Autism spectrum disorders; diagnosis; causes; intervention; adult outcomes.

Introduction

Autism Spectrum Disorder (ASD) is a pervasive developmental disorder affecting many areas of functioning. The core symptoms are deficits in social communication and social interaction, and restricted, repetitive patterns of behaviour, interests or activities. Many individuals with ASD also experience sensory difficulties, such as hypo- or hyper-sensitivity to light, sound, colour, smell, taste or touch.

The term 'spectrum' is used to indicate the wide range of abilities and difficulties associated with ASD. Intellectual ability can range from profound disability to superior intelligence; some individuals have no use of and/or minimal understanding of language while others have well developed vocabularies; symptom severity can also vary from very debilitating to relatively mild.

Diagnostic criteria

The most recent version of the US based Diagnostic and Statistical Manual (DSM-5; APA, 2013) specifies the following diagnostic criteria (see Table 1):

DSM-5 criteria state that symptoms must be present in early childhood but may not become fully manifest until social demands exceed capacities. Symptoms need to be functionally impairing and DSM-5 identifies three severity levels, depending on the amount of support required:: Level 1 (needing some support); 2 (needing substantial support); 3 (needing very substantial support). However, there is a lack of clarity about how these levels should be defined. DSM-5 also lists a number of specifiers that identify individual characteristics, i.e.: with/without accompanying intellectual impairment; with/without language impairment; associated with known medical or genetic condition or environmental exposure, or with another neurodevelopmental, mental or behavioral disorder.

The latest draft of the International Classification of Diseases (ICD-11; WHO 2018) generally follows DSM-5 in grouping symptoms into two core domains: (i) persistent deficits in the ability to initiate and sustain reciprocal social interaction and social communication; (ii) a range of restricted, repetitive, and inflexible patterns of behavior and interests. However, there is less emphasis on sensory sensitivities. To meet diagnostic criteria, symptoms must cause functional impairment although symptom severity may vary according to social or other contexts.  To reflect the wide range of ability in ASD ICD-11 also proposes that intellectual disability should be specifically rated as present/not present and functional language should be categorised as no/mild impairment; some impairment; no functional language. The validity and stability of these subdivisions are still to be established.

DSM-5 and ICD-11 diverge from their predecessors (DSM-IV and ICD-10) in that diagnosis is based on deficits in two core domains. Previously, diagnostic criteria specified deficits in three domains: communication; reciprocal social interaction, and restricted, repetitive, and stereotyped patterns of behaviour and interests). However, subsequent research demonstrated that deficits in communication and reciprocal social interaction almost invariably co-occurred and these two domains were combined. In a further departure from DSM-IV and ICD-10, ASD is no longer divided into sub-categories (i.e. autism, autistic disorder, atypical autism, Asperger syndrome/disorder; Pervasive developmental disorder not otherwise specified {PDD-NOS}). Again, this decision was based on data demonstrating the lack of reliability of these separate diagnoses.  Concerns have been raised that individuals formerly diagnosed with these conditions could lose their autism diagnosis under the revised criteria and thus be denied necessary medical, social, educational or financial support. However, DSM-5 explicitly states: “Individuals with well-established DSM-IV diagnoses of autistic disorder, Asperger's disorder, or pervasive developmental disorder not otherwise specified, should be given the diagnosis of autism spectrum disorder”.

Prevalence

Although ASD was once considered a very rare condition, prevalence estimates have risen steadily over past decades and recent reviews suggest rates of around 1% to 1.5% (Lyall et al., 2017), However, differences in sampling, screening, diagnostic instruments and ascertainment methods, mean that estimates vary widely from one study to another and the validity of much survey data remains in doubt (Fombonne, 2018). Nevertheless, it is clear that the numbers of individuals diagnosed with autism across the world have increased significantly over recent decades. Most evidence suggests that this growth reflects improvements in diagnostic practice and much greater awareness of ASD among the general public, and within clinical, social and educational services. Whether or not there has been an actual rise in prevalence has still to be demonstrated.

Early symptoms

The first signs of ASD are often evident by 18 to 24 months, with the earliest symptoms being associated with problems in social relating, reciprocal communication and/ or lack of imaginative play. Ritualistic and stereotyped behaviours may not become apparent until children are older - around 3-4 years. The preschool period (4-5 years), when children have to relate more closely with their peers, is often the time when autistic symptomatology becomes increasingly apparent. A quarter to one-third of parents report that, following an apparently normal period of development, their children lose speech and sometimes social skills around 18-24 months (Barger et al., 2013). The causes of such regression remain unknown but loss of skills tends to be more frequent in children of lower cognitive ability and in those with epilepsy or epileptoform activity.

Gender ratio

Like many conditions involving language impairments, the diagnosis of ASD is more frequent in males than females. The overall male:female ratio is estimated at around 3:1 (Loomes et al., 2017), although there is considerable variation between studies. Moreover, there are concerns that, because of subtle differences in the manifestation of ASD symptomatology in females, many girls and women who meet criteria nevertheless fail to receive a diagnosis. Until this diagnostic bias can be resolved the true male to female ratio will remain uncertain.

Diagnostic assessment

Although the typical age of diagnosis has decreased over recent decades many children do not receive a formal diagnosis until they are 4 or 5 years of age or even later. There is also great variation both within and between countries, with average age of first diagnosis ranging from 38 to 120 months (Brett et al., 2016; Daniels & Mandell, 2014). Family factors associated with delayed diagnosis include greater social deprivation and lower social/educational level. Diagnosis is also likely to be delayed in children with less severe autism symptoms or those who do not show a 'classic' picture of autism. This can particularly apply to girls, individuals with severe intellectual disabilities, or those who have additional sensory, physical or genetic impairments (deafness, blindness, Down's syndrome, cerebral palsy, etc).

There are no reliable bio-markers for ASD and hence diagnosis relies on the identification of a constellation of specific symptoms. Deficits in the core diagnostic domains must also be distinguished from deficits that may be attributable to factors such as low IQ, sensory impairments, or other developmental or psychiatric disorders. Valid diagnostic assessment relies on clinical observation, caregiver reports and a detailed developmental history. UK Nice Guidelines for both children and adults (2011; 2012) recommend that assessment should be conducted by a multidisciplinary team and that diagnosis is made on the basis of expert clinical judgment.

Diagnostic instruments

Although no single autism-specific instrument is recommended to diagnose ASD (NICE, 2011), a number of standardised instruments is available to enhance diagnostic accuracy. Table 2 lists commonly used screening instruments designed to identify individuals at risk of having ASD and who, if they approach suggested cut-off criteria, should be referred for a full diagnostic assessment (see also Hirota et al., 2018; McPheeters et al., 2016;).Table 3 lists measures that provide a structured framework for the detailed assessment of developmental and behavioural functioning and can be used as part of a more formal clinical assessment.  Interview-based information from carers may also be supplemented by standardised observational measures.

Cognitive assessments

The diagnostic process should also ­incorporate assessments of cognitive and verbal ability. Psychometric tests suitable for use with young children with ASD include the Mullen Scales, the Merrill Palmer Scales, the Bayley Scales and the Wechsler Pre-School and Primary Scale of Intelligence; a wide choice of language tests is available (see Charman et al., 2017). Cognitive tests for older children and adults include the Wechsler scales (WISC, WASI & WAIS) and the Raven’s Matrices. The Vineland Adaptive Behavior Scales (Sparrow et al., 2005) can be helpful for assessing very young or severely intellectually impaired individuals, as they are based on carer information and can be used to assess functioning in several domains and across a wide age range. A combination of different methods - observational, carer-based and standardised assessments - is recommended in order to obtain a valid picture of an individual’s functioning across a range of different areas and contexts (Grondhuis et al., 2018).

Physical examination

Rates of physical problems in autism are high (Croen et al.,2015; Zerbo, 2018) and a comprehensive examination should be conducted to identify additional physical or neurological disorders. It is important, too, to assess vision, hearing and motor skills, as impairments in these areas may significantly affect general functioning. Routine neuroimaging is unlikely to be justified, unless there are unexplained changes in behaviour or loss of skills.NICE (2011) does not recommend routine genetic testing but suggests this should be done if there are specific dysmorphic features, congenital anomalies, other evidence of a learning or intellectual disability, or a family history of developmental disorders. However, whole genome sequencing is becoming increasingly more common across Europe and the US.

Epilepsy occurs in around 20-25% of individuals with ASD (Besag, 2018), but may not develop until the early teens, and it is important to be alert to the possibility of seizures if sudden, unexplained changes in behaviour occur. EEG abnormalities are also common but, in the absence of other symptoms, are not in themselves an indication for anti-epileptic medication.

Differential diagnosis

Research suggests that 70% or more of individuals with ASD meet criteria for one or more other disorders (APA, 2013; Mansour et al., 2017; Simonoff et al., 2008). These include intellectual disability, language disorders, specific learning disorders, ADHD, irritability and aggression, tics, and eating, sleeping and elimination disorders. Mental health problems, particularly anxiety and depression, are common in adolescence and adulthood. Routine screening, and treatment, for frequently co-occurring disorders should be part of any diagnostic assessment since these conditions can significantly reduce the quality of life of individuals with ASD and their families.

ASD is also more common in many genetic disorders than in the general population. These include Fragile X syndrome, Down syndrome, Rett syndrome, Cornelia de Lange syndrome, Tuberous Sclerosis Complex, Angelman Syndrome, Neurofibromatosis Type 1; Noonan syndrome; Williams syndrome, 22q11.2 deletion syndrome and many others (Richards et al., 2015). There is an increased risk of ASD among children who are profoundly deaf and those with congenital blindness (e.g. Do et al., 2017). However, families of children with an identified genetic or sensory disorder often find it very difficult to obtain a clinical assessment of ASD as many professionals tend to attribute all the child’s problems to the original diagnosis, even when development is atypical for that condition.

A number of other conditions affecting early development may be confused with ASD including developmental language disorders, severe psychosocial deprivation, profound intellectual impairment, selective mutism, early childhood schizophrenia, childhood disintegrative disorders and Landau-Klefner syndrome. However, the onset, course, response to intervention and family background in these disorders are generally different from those found in autism. In most cases, a detailed developmental and family history, together with careful physical, psychometric and linguistic assessments will avoid diagnostic confusion.

Causes

Genetics. Theories about the causes of autism have changed markedly over the years. When the condition was first described (Kanner, 1943) inadequate parenting was often considered to be the primary cause. However, it is now evident that families with one autistic child have a significantly increased risk of having other children with ASD. Family genetic studies have also identified very high concordance rates among monozygotic twins, and increased rates of social and communication difficulties and circumscribed interests or repetitive behaviours among relatives (Bolton et al.). In addition, there is an increased familial risk of depressive disorders. Currently ASD is recognised as a highly heritable genetic disorder that may be caused by multigene interactions or arise from spontaneous mutations in genes with major effects. A wide range of common and rare variants associated with ASD has been identified but these can differ from one individual to another. Many of the ASD-risk genes that have been identified are involved in chromatin remodeling, regulation of protein synthesis and degradation, or synaptic plasticity (Bourgeron, 2015).

Environment. Possible environmental factors linked with an increased risk of autism include higher parental age and a history of sub-optimal pre-or perinatal development (e.g. medication use in pregnancy; maternal obesity, hypertension or infection; Modabbernia et al., 2017). While there is no evidence that vaccination (notably the MMR vaccine) is associated with an increased risk of ASD, the potential impact of other environmental influences is still a focus of ongoing research.

Neurobiology. It is now generally accepted that autism is not due to impairment in a specific brain region or system but to widespread and diffuse effects on brain connectivity that affect perceptual, attentional, motor and social systems from the first year onwards. These effects become more evident when multisensory integration becomes important and it is then that key regions of the social brain may be particularly vulnerable to disruption (Elsabbagh & Johnson; 2016). Individual differences in sensitivity to the environment and different learning styles can subsequently result in very different developmental trajectories and may explain the very heterogeneous profiles of skills and deficits that characterise autism.

Cognitive and language ability

Estimated rates of intellectual disability in ASD vary widely and are influenced by the intelligence tests used and the samples of children involved. Data from a recent US survey (Centers for Disease Control and Prevention, 2018) found that, among children with ASD, 44% had an IQ score in the average range (i.e. IQ ≥80), 24% scored in the borderline range (IQ 70-84) and 32% had intellectual disability (IQ score ≤70).

Verbal skills are generally more severely impaired than non-verbal skills but although the acquisition of language is typically delayed, around 70% of individuals with ASD develop some speech and over 40% - mainly those of higher IQ and with less severe autism symptoms - attain fluent speech (Wodka et al., 2013). However, language comprehension, particularly related to more complex or abstract language is typically poorer than expressive language.   This can give rise to difficulties since the relatively good spoken vocabulary of many individuals with ASD often gives a misleading impression of their true level of competence and understanding.

Interventions for autism

There is no evidence for treatments that claim to result in cures or recovery from autism. Moreover, many widely used interventions such as dietary and vitamin treatments, music therapy and sensory therapies have very limited evidence of effectiveness (NICE, 2013). NICE guidelines also discourage the use of a number of specific treatments (see Table 4).

In recent years there has been growing evidence for the effectiveness of parent-mediated treatments that focus on the joint interaction between very young children and their caregivers. These include the Early Start Denver Model (ESDM), Joint Attention Symbolic Play Engagement and Regulation (JASPER) and Preschool Autism Communication Therapy (PACT) (see Lord et al., 2018). There is also moderate evidence for a number of programmes based on Applied Behaviour Analysis. These include Enhanced Milieu Teaching (EMT), Incidental teaching (IT), Pivotal Response Treatment (PRT), Reciprocal Imitation Training (RIT) and Social Communications/Emotional Regulation/Transactional Support (SCERTS) (Reichow et al., 2018). For older children, various social skills interventions have been found to improve social competence and understanding (Ke et al., 2018). Cognitive behavioural interventions to reduce anxiety also report moderate to high effect sizes (Lord et al., 2018).  High quality intervention research for adults is much more limited, although there is some evidence for the effectiveness of cognitive behaviour therapies (including mindfulness) for reducing anxiety and depression (Spain et al., 2017); supported employment schemes may also help to improve job finding and retention (Mavranezouli et al., 2013)

Medication

NICE guidelines (2013) highlight the fact that there are no medications that should be used for the management of core autism symptoms.  However, pharmacological interventions can be important in treating common co-occurring disorders such as irritability, agitation, ADHD, epilepsy, anxiety and mood disorders,

ASD in adulthood

Despite the fact that ASD is a life-long condition, much past research into diagnosis and treatment has focused on children. However, more recent studies have begun to highlight the needs and skills of adults.

Diagnosing ASD in adulthood

For individuals who remain undiagnosed during childhood but continue to show difficulties as they move through adolescence and into adulthood, NICE (2012) highlights a number of characteristics that should alert clinicians to the need for a full assessment of possible ASD (See Table 5).

Several of the diagnostic instruments initially designed for children (e.g. ADI-R) can be used reliably with adults. Although there may be problems in finding an appropriate informant if parents are deceased or very elderly, a satisfactory developmental history can frequently be obtained from siblings or other relatives. The ADOS also has a module that is specifically designed for adolescents and adults. Screening instruments include the AQ, RAADS-R and SRS (see Table 2).

Outcome in adulthood

Among the strongest predictors of a positive outcome are the development of language and having a non-verbal IQ in or around the average range (Lord et al., 2018). However, it is evident that outcome in adulthood, even for individuals of average IQ or above is often poor (see Howlin & Magiati, 2017).  Most people with ASD show improvements in many aspects of their development as they grow older and the severity of autism symptoms also tends to decrease over time. Nevertheless, access to higher education and employment is limited and follow-up studies suggest that fewer than a third of adults are in full-time employment. The majority remains dependent on families and/or state benefits for support and only a minority develops close, long-term relationships. There are few evidence-based interventions for adults and specialist help and support is particularly limited for individuals of average or above intelligence disability. Very many adults with ASD experience mental health problems that can greatly impair functioning and reduce quality of life and it is suggested that the constant demands of ‘fitting-in” to a non-autism world, and the absence of appropriately structured support or daily activities, all contribute to high levels of stress, anxiety and depression.

Physical problems and chronic health disorders are also more common than in the general population (Croen et al., 2015; Zerbo, 2018) and recent studies highlight the risk of premature mortality in ASD (Hirvikoski et al., 2016). Premature mortality is particularly high in adults with intellectual disability and epilepsy. In individuals of average or above average IQ suicide is a significant cause of premature death.

ASD in older adults

Very little is known about the lives of older individuals (i.e. 60 years+) and there is little information on whether, compared with the general population, these individuals show greater cognitive deterioration with age, or whether they show areas of relative preservation or strength. Although this theory is yet to be proven there is some evidence that, while verbal memory in ASD shows a similar decline as in “typical” ageing, visual and working memory skills tend to be better preserved. There may also be less deterioration in mental health and in overall quality of life in older adults with ASD than in the general elderly population (Roestorf & Bowler, 2016).

Conclusion

Understanding of ASD has improved significantly over recent decades.  It is now accepted that this condition is far more common than was once thought, that it can affect individuals of all cognitive levels, and that, in the majority of cases, it is genetically determined. However, more is still to be learned about the genetic mechanisms involved, and how these affect brain development and brain function throughout the life-span. Finally, thanks to a growing movement among individuals with ASD themselves, it is becoming increasingly recognised that ASD can be associated with many positive skills and potential benefits. Providing individuals with an inclusive and supportive environment that encompasses their “differences” and promotes well-being, rather than focusing only on deficits and difficulties, is a major challenge for the decade ahead.

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This article was published on this site in October 2018. It replaces the article previously published on this site in 2002.