What are autism spectrum disorders? - Chapter 26

What disorders fall under autism spectrum disorder?

'Autism spectrum disorder' (ASD) is a broad term that includes three developmental disorders: Asperger's syndrome, PDD-NOS, and autistic disorder. These disorders are diagnosed by using two domains: persistent deficits in social communication and social interaction across multiple context, and restricted, repetitive patterns of behaviour, interests, or activities. Kanner and Asperger (psychiatrists) described the typical characteristics of autism in the middle of the last century.

How is ASD classified?

According to the DSM-IV, for the diagnosis of autistic disorder both domains (as mentioned above) must be disturbed. One of these should already manifest itself before the age of 3. For the diagnosis of ‘Asperger's syndrome’, there should be no problem in the development of language, but there must be one limitation in the stereotypical interests and behaviors, and two limitations within the domain of social interaction. Pervasive developmental disorder not otherwise specified (PDD-NOS) is a residual category where the patient experiences persistent limitations in social interaction but the criteria for the other two diagnoses are not met.

What is the clinical picture?

How is an adult diagnosed with ASD?

In the past, the focus was mainly on children and young adolescents, but recently more attention has been paid to adults with ASD. However, this diagnosis is a lot more complex for five reasons:

1. Usually milder forms within the autism spectrum are involved.

2. Over time, patients have learned to adopt social behaviour that compensates for and masks their autistic symptomatology.

3. Many comorbid disorders.

4. The differential diagnosis between ASD and an anxiety disorders (in particular, social phobia and obsessional neurosis) and schizophrenia is difficult to make. The differential diagnosis with schizophrenia is difficult because ASD patients tend to generate psychotic symptoms in the case of increasing stress.

5. Finally a developmental anamnesis is very important in the (differential) diagnosis and this is difficult to achieve in adulthood.

What common characteristics do people with ASD have?

Almost all ASD patients avoid eye contact (adults have taught themselves this although they often stare). In addition, they do not support their spoken words with gestures that make them appear stiff. Their overall motor skills are also stiff and awkward. A patient with Asperger's syndrome often has a very formal language. ASD patients depend on others to bring structure to their lives. During the interview, the ASD patient cannot properly cope with social norms such as speaking alternately, noticing when the conversation partner is no longer interested and taking into account the prior knowledge of the other. For this reason, ASD patients also take little initiative to conduct interviews and they often respond with short answers. ASD patients place a high value on fixed routines and get upset when they deviate from this. Their information processing focuses on the details and presents problems when meaning has to be given to the stimuli.

Is ASD often diagnosed?

Some speak of an autism epidemic because there have been so many ASD diagnoses in recent decades. This is probably not caused by the disorder itself, but by earlier recognition, broadening of definitions and improved diagnostics. The male to female ratio is 4: 1.

What are the aetiology and neuropathology of ASD?

The role of genes

ASD is about 90% genetically determined. Some 'single gene disorders' such as fragile X syndrome and tuberous sclerosis are associated with autistic symptomatology. However, ASD usually results from a combination of multiple genes in interaction with (yet unclear) environmental factors. There are nearly 40 chromosomal regions that are related to ASD and more specific research is needed. There are already indications that chromosomes 1, 15 and 17 would be related to rigidity and obsessive-compulsive behaviour and chromosome 2 and 7 are associated with language development problems.

The role of the cerebrum

20% of ASD patients have macrocephaly (a head circumference that is 2 SD larger than the population average). This is due to growth in brain matter (not due to more cerebrospinal fluid), especially the frontal and temporal lobes are larger. In the first years of life there is a strong increase in brain volume; after the fifth year of life the volume increases less than in healthy controls. White matter abnormalities affect the exchange of information between the various brain regions: adults with ASD do indeed have less connectivity and integration between the networks (supported by imaging data). Although the brain volume is larger, the corpus callosum is smaller, which may limit information exchange between the two hemispheres.

The role of the limbic system and cerebellum

In the limbic system (including the hippocampus and the amygdala) there is a higher cell density, with smaller cells. The amygdala is activated less in ASD patients (hypoactivity) when a face has to be recognized or when ToM is requested. This is probably the result of a non-specific effect: lower emotional arousal with social stimuli. The amygdala shows hyperactivity when ASD patients have to look someone in the eye: this is associated with social anxiety. There are no deviations in the activity of the fusiform face area (FFA). In the cerebellum, fewer Purkinje cells are found in the posterior inferior parts. This is related to attention problems and motor clumsiness. A new interesting point of view is the suggestion that the mirror neuron system (also involved in ToM, language and empathy) functions less well.

What are the neurochemistry and endocrinology of ASD?

Due to the lack of good control groups, small samples, and the great heterogeneity of ASD, no clear conclusion can be drawn from neurochemical studies. The medication focuses primarily on comorbidities such as anxiety complaints, restless behavior and psychotic symptoms. Although the overall serotonin level does not seem to differ between ASD patients and controls, there is a deviation in the course of serotonin production in the CNS: ASD children have a reduced production in the thalamus and the frontal cortex until the fifth year of life, when production increases gradually. In the peripheral nervous system, serotonin levels are increased in one third of ASD patients (this is not specific for ASD patients: this is also found in Huntington's disease, schizophrenia and mental retardation). In animal studies this would be related to a lower need for social attachment, but in humans the functional importance has not been demonstrated yet.

What cognitive explanatory models are there?

There are two models that try to explain impairments in social interaction, communication, and behaviour. Two other models, the Theory of Mind (ToM) and the model of disturbed executive functions, are more descriptive models.

Theory of Mind

Baron-Cohen, Leslie and Frith (1985) were the first to adopt a ToM paradigm for children with ASD. ToM is the ability to put oneself in someone else's thoughts, feelings and intentions to understand and predict another person's behaviour. ToM tasks suggest that there is not a disorder in ToM, but the development of ToM skills would be delayed. However, even in adulthood, ToM tasks are performed well while there are problems in social interaction. This discrepancy has two possible explanations:

1. The ToM tasks in the test situation are relatively simple compared with the situations that are encountered in real life. Adults with ASD and normal intelligence have been shown to experience more problems with complex tasks involving perspective taking than healthy controls.

2. People with ASD make little spontaneous use of ToM in daily life, even if their performance on ToM tasks is unimpaired.

This latter hypothesis is almost universally accepted. ASD patients deal with the lack of spontaneous 'mentalising' by teaching themselves compensatory mechanisms to bypass neurophysiological limitations.

The theory of central coherence

Frith (2003) stated that ASD patients have a weak central coherence (CC): information is not automatically processed globally and according to context, but instead they process information in a fragmented way and at a local level. This is a stylistic feature rather than a defect. This theory explains why children with ASD were better than controls in on the following tasks:

• The Hidden Figure Test (the child must discover a certain element in a larger meaningful figure as quickly as possible).

• Block patterns (the child must build a block pattern as quickly as possible);

• Verbal memory tasks (ASD children are not influenced by the word meaning).

According to Teunisse and colleagues (2001), the CC is related to a weak piecemeal processing and a processing of meaning. This makes CC not a homogeneous concept. Happé and Frith (2006) conclude that CC is not a disorder in recognizing a meaning or seeing the whole (this is because ASD patients can get it if they get directions), but that there is a strong bias to get the information on a local level.

The model of the different executive functions

Ozonoff, Pennington and Rogers (1991) introduced the idea that abnormal executive functions are responsible for ASD symptoms. Disorders in the following executive components are consistently reported in relation to ASD patients: planning, inhibition, self-monitoring, the generation of new ideas and cognitive flexibility (the latter is typical of ASD). There are, however, many conflicting results in the literature that are listed according to Kenworthy, Yerys, Anthony and Wallace (2008):

• Do structured tasks within the standardized setting really measure executive functioning? What is executive functioning?

• Different tasks measure different multifactorial components.

• The social interaction between test leader and test subject influences performance (ASD patients perform better on the same task that is taken on the computer in the absence of a test leader).

The emphatising-systemising theory

An interesting hypothesis by Baron-Cohen (2002) is the 'extreme male brain theory of autism': ASD is an extreme form of male (systemising) thinking. Feminine thinking is related to emphathizing. The theory is often better known as the 'empathising-systemising theory' (ES theory). With this, Baron-Cohen explains the social and non-social characteristics because of the distinction between empathy (weak) and analytical analysis (superior). This hypothesis is supported by correlational studies that have looked at prenatal exposure to high testosterone levels and the thinking style in the healthy population: research in ASD patients is still needed.

Is ASD a single disorder?

In the DSM-5, more account is taken of heterogeneity. Instead of the subdivision into subcategories, three levels of severity will be introduced. These are based on the amount of support required. The three domains of behavioral symptoms are also shortened to two: (1) social and communication problems and (2) stereotypical interests and behaviors. The language deficiency will no longer be seen as a typical symptom of autism, and will be removed.