Strange ways of autism

April 4, 2020 0 By S Harachand

Autism Spectrum Disorder (ASD), one of the most prevalent neurodevelopmental disorders, is increasing at an unprecedented pace in various regions of the world over the past several years.

Currently, the disorder affects 1 in 59 children in the US. In the UK, 1.1% of the population may be on the autism spectrum, show the latest prevalence studies.

Autism is not a disease, but a syndrome. People with autism behave differently. Every person with autism is different. They communicate, interact, learn and react to things in ways that are different from most other people.

The mental abilities of autistic people range widely. While some people with ASD need a lot of help in their daily lives, others appear gifted with special talents.

Many autistic people are ‘high functioning’, meaning the person can participate fully in everyday society. 

Starting in early childhood, signs of ASD typically last throughout a person’s life.

Certain disease conditions, including fragile X syndrome, tuberous sclerosis and epilepsy, increase the risk of autism.

Triad of impairments

The diagnosis of autism has changed over the years. It has now been broadened to include several conditions that used to be diagnosed separately such as autistic disorder, pervasive developmental disorder not otherwise specified (PDD-NOS), and Asperger syndrome. A diagnosis of ASD is often arrived at by looking at a person’s behaviour and development. 

Some experts believe that ASD can usually be reliably diagnosed by the age of two. 

The American Academy of Pediatrics recommends that all children be screened for developmental delays at their 9, 18, and 24 or 30-month well-child visits and specifically for autism at their 18 and 24-month well-child visits. 

Additional screening is warranted if a child is at high risk, including children who have a family member with ASD, have some ASD behaviours, have older parents, have certain genetic conditions, or who were born at a very low birth weight.

Many children, however, do not receive a final diagnosis until much older. This is partly because of the wide variance in early signs of autism. 

Some infants show some indications in their first months. In others, such tendencies become obvious as late as age 2 or 3. Not all children with autism show all the signs. Many children who don’t have autism show a few. 

ASD is distinguished by a characteristic triad of symptoms: impairments in social interaction, impairments in communication, and repetitive behaviour.

The concept of the triad of impairments as the central plank of the construct of autism, dating back to the 1970s, has evolved over the years.

Researchers now argue that the actual triad of impairments is at the level of cognitive processing, and not necessarily in its variable and fluctuating behavioural manifestations.

They also suggest the actual triad of impairment in autism is visual, as opposed to linguistic, processing, impaired abstraction, and lack of theory of mind.

Intriguing inheritance

Genetics and neuroscience have identified intriguing patterns of risk, but without much practical benefit yet.

Studies provide overwhelming evidence for a biological basis and a strong genetic component for the neurodevelopmental disorder, virtually abandoning early suggestions that ASDs might result from abnormal parenting.

The genetic component in ASD, however, is diffuse. A large number of gene variants have been implicated in the development of ASD. Some of these common genetic variations are found to have little effect, while some of the rare ones show a large effect. 

CHD8 is one of the most common genes disrupted with a large effect. However, less than 0.5% of people with ASD have such a mutation. 

Even though genetic conditions like fragile X syndrome are strongly associated with some ASD, only around 2% of people with the disorder have fragile X, reports show.

As many as 98,785 structural variants (SVs) of genes were identified to have links with ASD, at an average of 5,843 variants per individual. A fraction of these were de novo mutations found frequently in the germline. The research community is now gathering more evidence on the SVs that play a possible role in autism, including the GRIN2B gene, the deletion of exons 8, 9, and 10 of the CHD2 gene or balanced translocation.

Studies so far have come up with no significant differences regarding the size of certain rearrangements in cases and controls. A slight increase in number, however, was found for cases relative to controls.

ASD has a tendency to run in families. Several research studies comparing autism rates in twins have shown that the disorder is highly heritable. When one identical twin has autism, chances are as high as 80% for the other twin to also have it. The corresponding rate for fraternal twins is around 40%.

Nevertheless, the inheritance pattern of ASD is largely unknown. People with gene changes associated with ASD generally inherit an increased risk of developing the condition, rather than the condition itself. When ASD is a feature of another genetic syndrome, it can be passed on according to the inheritance pattern of that syndrome, show studies conducted by the National Institutes of Health, US.

Environment — overhyped?

The latest studies highlighting ASD’s high reliance on inherited genes contradict the initial hypothesis that autism is an environmentally caused disease.

The contribution of the environment to ASD risk appears to be much smaller than the contribution of genetics, commented experts in a recent editorial that appeared in JAMA Psychiatry.

The role of maternal factors is almost non-existent. Unproven causes of autism, such as vaccines have been long-discredited.

Yet, many experts do strongly believe that environmental factors cannot be completely ignored. In particular, smaller, environmental factors and their interaction with genetic risk factors play an important role.

We are not yet able to identify a specific genetic cause for autism in many children, experts say.

“There are a few published research studies linking environmental pollution to ASD,” points out Wendy Fournier of National Autism Association, a British charity,  adding that possible environmental factors contributing to the massive increase in prevalence over the last 20 years have not been extensively researched. 

The increasing prevalence of autism has generated great interest in the potential involvement of toxins from the environment. For example, prenatal exposure to the chemicals thalidomide and valproic acid has been linked to an increased risk of autism.

Environmental factors act through epigenetic regulation. Epigenetics, which studies factors that control gene expression, involves chemicals that surround a gene’s DNA.

Hundreds of potential environmental factors have been suggested to contribute to the risk.

By the term “environment”, researchers refer to much more than pollutants and other chemical exposures. Parental age at time of conception, for example, is an environmental influence associated with an increased risk of autism. So are birth complications such as significant prematurity or oxygen deprivation.

Behind the male bias

Autism is diagnosed three times more often in boys than girls, as per data provided by the National Autistic Society, the UK’s leading charity for autistic people. The reasons for this are not yet completely clear.

It takes fewer of the structural variants to predispose a boy to developing autism than it does a girl. In other words, girls may be spared of autism even though they have the same number and kinds of genetic variants that cause the condition in boys.

Various theories try to explain this phenomenon, but often in a non-conclusive way.

Some argue that there is a female autism phenotype. Recent evidence points to a variety of autistic behaviours that present differently in girls. Studies trying to quantify clinical heterogeneity in ASD also indicate that verbal autistic girls and women behave differently than their male counterparts.

Currently used autism assessment tools are usually based on male characteristics, leading to under-diagnosis in females. 

Similarly, certain symptoms of autism are more common in boys than in girls. For example, repetitive behaviour and difficulty with impulse control may appear more often in autistic boys than autistic girls.

Moreover, autism in high functioning autistic children with average intelligence and social skills is more difficult to diagnose and some doctors may overlook it in girls.

Theories also postulate that women and girls are better at masking or camouflaging their difficulties during tests for autism.

Researchers are also exploring whether the effects of high levels of foetal testosterone is linked to male brain development.

Autism in adults — No sharp focus

ASD occurs in all age, racial, ethnic, and socioeconomic groups, according to the Centers for Disease Control (CDC). 

Earlier, it was far less common for researchers to look for autism in older adolescents and adults.

Diagnosing ASD in adults is often more difficult than diagnosing ASD in children. 

Even though severe forms of ASD are quite often diagnosed in the first two years of a child’s life, high-functioning individuals may not be diagnosed until much later in life.

Mild challenges that usually occur in adults with autism are sometimes mistaken for symptoms of attention deficit hyperactivity disorder (ADHD), while others will have more severe symptoms, like impaired spoken language.

Current estimates show that ASD prevalence is roughly one in 50 men, or one in 75 people of all ages are on the autism spectrum. There are 500,000 autistic adults in the UK, according to numbers provided by Autistica, a UK-based autism research charity. 

Rates were higher in men and those without educational qualifications. The prevalence of autism is significantly higher in people with moderate to profound intellectual disability.

Some researchers have been looking at individual cases of autism in adulthood, but there has been no coordinated research effort in this area and no big focus on autism in this age group. Similarly, there are not many practitioners specialised in autism in adolescents and adults.

Awareness of ASD in adults has grown dramatically in recent years, leading to an increase in diagnoses.

In the UK, more than half of the young adults with autism remain unemployed and unenrolled in higher education for the first two years after high school. This is a lower rate than that of young adults in other disability categories, including learning disabilities, intellectual disability and speech-language impairment, according to published data. 

The cost of caring for autism in the US was $268 billion in 2015 and is expected to rise to $461 billion by 2025 in the absence of more-effective interventions and support across the life span, reports indicate.

The majority of autism-related costs in the US are for adult services – an estimated $175 to $196 billion a year, compared to $61 to $66 billion a year for children.  

High vulnerability to diseases, accidents

Autistic people seem to be far more vulnerable to a surprising range of medical problems and they appear to die much earlier than the general population. Suicide and depression seem far more common than in the general population.

Comorbidities are likely to be difficult to recognise. The failure to identify the impairment is partly due to ambiguous symptomatology. 

It is not uncommon for people with autism to suffer from gastrointestinal disease, seizures, sleep disorders and more, says Wendy.  Often, these medical comorbidities are left undiagnosed and untreated as just a “part of autism”.  Not taking these medical issues seriously can result in extremely poor physical and mental health for the person affected, she alerts.

There is now a large body of research underscoring the increased risk of people diagnosed with ASD to be suffering from immune dysregulation, allergies, food sensitivities, GI disorders, excessive oxidative stress, mitochondrial and metabolic dysfunction, subclinical seizure activity and epilepsy. Research also shows that increased severity of many of these conditions correlates with increased severity of ASD.   

Drowning caused over 70% of accidental deaths in people with ASD, followed by fatal traffic injury, found a study conducted in the US by the National Autism Association during the 2011-16 period. Children 14 and younger faced higher lethal risk, and those under the age of 5 showed a significant risk with cases ending in death nearly 60% of the time. 

According to data published in 2012 by Pediatrics, 49% of children with an ASD attempt to elope from a safe environment, a rate nearly four times higher than their unaffected siblings.

Subsequent studies found that males are involved in a large majority of elopement cases compared with females.

Early interventions: Catch’em young

The outlook for individuals with autism spectrum disorder today is brighter than it was 50 years ago. Early interventions help more number of people with this condition to speak, read, and live in the community rather than in institutions. Some among them will be largely free from the symptoms of the disorder by adulthood, studies show.

Nevertheless, most such individuals will not work full-time or live independently.

Family training, speech therapy, hearing impairment services and physical therapy are among the early interventions that can bring about real progress in some children with ASD.

Early interventions for autism are more likely to have major long-term positive effects on symptoms and later skills. Such interventions occur as early as 2 or 3 years of age, when a young child’s brain is more “plastic”.

“By addressing developmental delays at the youngest age possible, a child is given a greater opportunity for improvement,” avers Wendy. 

Some of this is attributed to the belief that the brain is more “pliable” at a young age and able to make new neurological connections in areas that may be affecting typical development, she comments.  

A controlled 5-year study of intensive early intervention on autistic children less than 2½ years of age conducted by Autism Speaks found the IQs of the children in the intervention group had improved by an average of approximately 18 points, compared to a little more than four points in the comparison group. 

The intervention group also had a nearly 18-point improvement in receptive language (listening and understanding), compared to approximately 10 points in the comparison group.

Experts opine that considerable work is still needed to understand how and when behavioural and medical treatments can be effective and for which children, including those with substantial comorbidities. 

Clinicians can make a difference by providing timely and individualised
help to families navigating referrals and access to community support systems, say experts.