Autistic Spectrum Disorder – Nature or Nurture? Aware or beware?

Since April was ‘Autism awareness month’ internationally, this blog is a little different, aiming to raise awareness of autism and how adults with autism and its associated disorders might differ from the neurotypical.

In March 2014, the US government released figures estimating the prevalence of autism as being 1 in 68 boys and 1 in 189 girls (thus creating a ratio of male:female prevalence of almost 3:1)1. This means that in most communities and workplaces, there will be at least one member who has been diagnosed as being ‘on the spectrum’, due to the expression of a ‘complex behavioural phenotype’, which now includes atypical disorders such as Asperger’s Syndrome or High Functioning Autism (those with an IQ higher than 80 and with good verbal skills).

The Nature-nurture debate

It is now commonly accepted that autistic traits run in families. It has even been argued that such traits are cumulative, resulting in children that are more autistic than their parents1. Recent studies have centred on mutations contained within nonsense DNA, that is to say, DNA which does not code for protein-coding genes, per se, but rather molecular modulators of gene expression. Such modulators include ‘enhancers’, of which more than 100 are now known to be present more in the brain than other tissues of the body, resulting in a significant influence over brain development in utero. Traditional gene studies, which focussed upon protein-coding genes, would actually miss more than 95 % of the human genome, therefore it’s of little wonder that our understanding of developmental pathways in neurological disorders lags behind that of more physically symptomatic diseases such as heart disease, or cancer. This is partly due to the phenomenon of ‘environmental fixation’, whereby families (particularly mothers) were blamed for their child’s autistic traits, to the extent of being branded ‘refrigerator mothers’, alluding to the alleged coldness with which they raised their children2. Furthermore, Harlow (1972) described behaviours in his rhesus monkeys, deprived of maternal contact, that were concordant with those of the autistic children carefully described by Kanner3, perpetuating the theory that families were to blame for the atypical behaviour of their child.  Thus, the pendulum of scientific opinion has swung between the two extremes of ‘nature’ versus ‘nurture’. Current models propose that multiple genetic, epigenetic and environmental factors may contribute to the etiology of autism, with the last decade of research revealing a significant genetic heterogeneity4. In summary, no two individuals diagnosed with ASD or Asperger Syndrome are the same!

The vast majority of studies into autism focus on children, as do the strategies designed to enable those diagnosed on the spectrum to cope with ‘day-to-day life’. However, children become adults, raising the challenge of both adaptation to an environment designed for neurotypical adults and also diagnosis for those adults who form the ‘lost generation’, people who were previously excluded from a diagnosis of classic autism either through ‘camouflage strategies’ (particularly prevalent in girls who are more likely to copy peers and thus appear ‘neurotypical’ to the untrained eye) or adaptation strategies, whereby an individual copies the actions of a neurotypical colleague, learning social rules as one might study a recipe, or protocol. A school friend of mine was such a case. She wore the same clothes as her best friend, did the same hobbies and was academically outstanding. Yet she failed to progress in her chosen career and was diagnosed with Asperger’s Syndrome aged 41. Her career choice of course was influenced by that of her peers, rather than her strengths.

So are HFAs and Aspies always doomed to failure in the workplace? Much is made of the drawbacks of HFA/Asperger’s Syndrome – appearing dissociated or uninterested, difficulties with social interaction, inappropriate conversation and lack of eye contact leading to perceptions of not telling the truth or being disinterested in a particular task or employment role to mention but a few – but shouldn’t we focus more on what autism has to offer?

For example, they may have the ability to focus intensely and for long periods on a difficult problem. There is often an enhanced learning ability, although this often is not applied to subjects they are uninterested in – and therefore it may be necessary to play to the strengths of employees or students, rather than attempting to counter-act weaknesses. HFAs and Aspies often present no problems in a supportive, well-resourced educational institution and often do well academically if they can be stimulated by good teachers. People with HFA and Asperger’s often have intense and deep knowledge of an obscure or difficult subject and a passion for pursuing it in an organized and scholarly manner. This makes them more likely to excel in ‘niche’ topics, particularly neglected areas of research. They are usually intelligent, gifted, honest, hard workers when interested in a task and excellent problem solvers. People with high-functioning autism are thought to become excellent scientists and engineers or enter other professions where painstaking, methodical analysis is required.

So should we beware of Autism? Or accept what it has to offer? Besides, what exactly is normal?

Blog written by Diane Lee, who has recently moved to the School of Veterinary Medicine at the Universityof Surrey.

1 Sylvie Goldman, MD, Albert Einstein College of Medicine, Opinion: Sex, Gender and the Diagnosis of Autism – A Biosocial View of the Male Preponderance (p.1-2)

2Judith Miles: Autism spectrum disorders—A genetics review; Genetics in Medicine (2011) 13, 278–294; doi:10.1097/GIM.0b013e3181ff67ba

3Kanner L. (1949). Problems of nosology and psychodynamics of early infantile autism. Am. J. Orthopsychiatry 19, 416–426

4Geschwind D. H. (2008). Autism: many genes, common pathways? Cell 135, 391–39510.1016/j.cell.2008.10.016

Epigenetics: The sins of the father

In the recent paper in Nature (2014, vol 507, p. 22-24), Virginia Hughes reports the experiments carried out by Dr Dias and Dr Ressler from the University of Atlanta in recent years. They have studied the involvement in inheritance imprints in mice as a result of a fear-based reaction associated to acetophenone. As a result, they found a larger than normal expression of M71 glomeruli receptors in their offspring’s noses. These receptors are encoded by a single gene, known as Olfr151.

This elegant, but still inconclusive cause-effect mechanism approach, brings a possible explanation to a controversial observation back to the 19th century when French biologist Jean-Baptiste Lamark pointed out the pass of acquired traits to future generations. Since then, scientists have observed this phenomenon in plants, animals and even humans.

Although some scientists are still sceptical about the transmitance method, nobody denies the phenomenon. Finding an explanation to this complex problem would involve a deeper study on reproductive biology and to study both mother and father lines over few generations.

The strong suggestion that this heriditary transmission of environmental factors is due to epigenetics, a concept introduced in the 2000’s, where there are some changes in the way that DNA is packed and expressed without altering its sequence, is one of the strong lines of thought, where chemical tags (methylation) on DNA can turn genes on and off.

But even if epigenetics is directly involved in the inheritance, through marks on the material contained in the sperm, the first question to be addressed would be to understand how the effects of environmental/ health legacy get embedded into the animal’s germ cells.

Epigenetics is still unable to explain how this observed phenomenon gets passed down through multiple generations, surviving several rounds of genetic re-programing. Other suggested agents might involve histones (proteins which has been observed that they can be passed down through generations) or short RNA molecules which role would be to latch on DNA and affect further into gene expression.

Scientists are optimistic about finding a cause-effect relationship in the years to come for a phenomenon which has proved elusive for researchers in the past hundred years.