Autism spectrum disorders (ASD), as defined by the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5, American Psychiatric APA 2013) are neurodevelopmental conditions diagnosed on the basis of a dyad of behavioural impairments: impaired social-communication, alongside unusually narrow and repetitive interests and activities.
The word “Autism” was coined in 1908 and used to describe a form of schizophrenia where patients were seen as withdrawn and self-absorbed. The first recorded description of a mild form of Autism, observed in six boys, was in 1926 by Russian neurologist Eva Sucharewa. It was not until 1944 that Hans Asperger, a Viennese paediatrician, defined “Autistic psychopathy” which was very similar to the definition published by Sucharewa. Asperger identified in four boys “a lack of empathy, little ability to form friendships, one-sided conversations, intense absorption in a special interest, and clumsy movements”, and called them “little professors”. Leo Kanner, an Austrian-American psychiatrist, made an independent observation of Autism almost simultaneously, in 1943 where he described the fundamental issue to be a child’s inability to relate to people and objects in an ordinary way. Kanner called this “extreme aloneness”, and observed that children with this condition had an anxious and obsessive desire for sameness and this resulted in their repetition of actions and limited spontaneous activity, and an inability to establish any relationships, experiencing extreme aloneness from very early on. Asperger’s description seemed to differ from Kanner’s as, unlike Kanner, he observed in his children high non-verbal intelligence and use of appropriate vocabulary. Asperger’s syndrome is often considered to be a high-functioning form of autism.
In 1966, the first epidemiological study estimated a prevalence rate of 4.5 out of 10,000 individuals. The prevalence has considerably risen since, especially in individuals without learning disability. Two to three times more males are affected than females although historically, females with autism might have been under-diagnosed.
Various risk factors are associated with Autism, such as interaction of gene and environment, germline mutations,or pregnancy related complications including exposure to toxic chemicals.
Signs of Autism are rarely observed at birth. Rather, Autism emerges through a process of diminishing, delayed or atypical development of social communication, starting between the ages 6 and 12 months.
Multiple independent cortical areas in the temporal, frontal and occipital lobes are affected in Autism. Many major structures of the brain including the limbic system, cerebellum, corpus callosum, basal ganglia and brainstem are also affected. Studies have also shown structural abnormalities and inflammation in the brain associated with Autism. Gene expression patterns in the Autistic brain are also significantly different from typical brains.
Understanding the genetic causes of Autism has proved extremely challenging. Genetic contribution towards Autism is approximately 61.9%, while 38.1% maybe environmental. Dozens of Autism risk genes have been identified, and hundreds of unique combinations of mutations in these risk genes can be associated with an Autism diagnosis.
Study of environmental factors in Autism involves resource intensive biochemical methods using a model organism. Being a complex behavioural condition it is a challenging task to model Autism in animals.
An adult induced pluripotent stem cell (iPSC) model can be used to study the neurobiology of Autism. iPSCs recapitulate tissue-specific fates like in the embryo, enabling faithful differentiation into any cell type following most of the stages that a foetus undergoes during pregnancy. Human iPSCs can be used to generate neurons and primitive brain-like structures (called minibrains) from donors, to study brain development using the information coded in their genome. Neurons and minibrains can be grown to desired time points to investigate molecular features similar to those present in the developing foetal brain. Atypical features associated with autism can be identified, and then correlated to clinical diagnoses.
Various groups in USA and UK are adopting this kind of biomedical research, and some of these studies have already identified common molecular mechanisms associated with Autism. These studies have shown precocious neuronal development in Autism, along with greater immune activation. Further studies will be required to pinpoint exact mechanisms responsible for the above molecular phenotypes, and what approach is needed to ameliorate these phenotypes.
Autism being a complex condition might never have a cure. But it is the aim of the scientific community to reduce its symptoms as much as possible so that individuals with Autism do not suffer because of it. Biochemical and neurobiological research using stem cell models can provide answers to help develop novel therapeutics to make Autism manageable.
Autism is often also accompanied by comorbid conditions such as epilepsy and muscular conditions, or depression and attention deficit disorders. Biomedical research can also help make breakthroughs to reduce these symptoms.
It is hoped that with the current pace of progress made in the field of scientific research into Autism and related neuropsychiatric conditions, we will have major therapeutic breakthroughs in the next decade to improve their lives.
Written by Dr. Dwaipayan Adhya
(Post-doctoral Research Fellow in Prof. Simon Baron Cohen’s laboratory at the University of Cambridge, England)