A thorough review of history shows that autistic people have always been part of the human community, though they have been relegated to the margins of society. For most of the twentieth century, they were hidden behind a welter of competing labels – Sukhareva’s “schizoid personality disorder,” Despert and Bender’s “childhood schizophrenia,” Robinson and Vitale’s “children with circumscribed interests,” Grandin’s initial diagnosis of “minimal brain damage,” and many other labels such as “multiple personality disorder,” which have fallen out of use.
In the wake of the vaccine controversy, society continues to insist on framing autism as a contemporary aberration – the unique disorder of our uniquely disordered times – caused by some tragic convergence of genetic predisposition and risk factors hidden somewhere in the toxic modern world, such as air pollution, an overdose of video games, and highly processed foods.
Currently, there are hundreds of studies from scientists around the world trying to understand the cause and treatment of this syndrome.
First, it is known that Asperger’s syndrome is not caused by inadequate parenting or psychological or physical trauma. The most general misconception about Asperger’s syndrome or autism spectrum disorders, in general, is that they develop because of poor parenting and a lack of bonding between parents and their children. This concept was even termed as ‘Refrigerator Mother’ to describe cold and distant parenting. But this notion was challenged in the 1960s when research on these neurological disorders started to grow and scientists found that it is not parenting, but rather the genetic and neurological makeup of the child that is responsible for these syndromes. Even today, the belief that neurodevelopmental disorders are caused by a traumatic childhood is common. The reality, however, is more complicated than our guesses based on limited information.
Parents should abandon feelings of personal guilt. Research has clearly shown that AS is due to a dysfunction of specific structures and systems in the brain. In short, the brain is ‘wired’ differently, not necessarily defectively, and this was not caused by what a parent did or did not do during the child’s development.
Brain imaging studies of typical people have identified the structures and systems that operate together to form the ‘social brain’. Asperger’s syndrome is associated with a dysfunction of the social brain – parts of the frontal and temporal regions of the cortex – to be more precise, the medial prefrontal and orbitofrontal areas of the frontal lobes, the superior temporal sulcus, inferior basal frontal cortex, and temporal poles of the frontal lobes plus dysfunction of the amygdala, basal ganglia, and cerebellum.
See http://www.ronperrier.net/2021/11/15/the-brain-in-aspergers-syndrome/
This is consistent with the psychological profile of abilities in social reasoning, empathy, communication, and cognition characteristic of Asperger’s syndrome. Why did those areas of the brain develop differently?
1. Genetic
Asperger originally noticed ghosting or shadow of the syndrome in the parents (particularly fathers) of the children he saw and proposed the condition could be inherited. For some families, there are strikingly similar characteristics in family members. Using strict diagnostic criteria for AS, about 20% of fathers and 5% of mothers of a child with AS have the syndrome themselves. Many have not had a formal diagnosis. If a broader description of AS is used, almost 50% of first-degree relatives of a child with AS have similar characteristics. When considering second and third-degree relatives, more than two-thirds of children with AS have a relative with a similar pattern of abilities. There is something in the genes.
Some of the characteristics have a detrimental effect on the person’s quality of life while others can be beneficial. Family members who have more AS characteristics than would be expected may have inherited beneficial characteristics that contribute towards their success in careers such as engineering, accountancy, and the arts. There is a greater-than-expected number of engineers among the parents and grandparents of children with AS. The children of such individuals may then be at greater risk of having even more characteristics, such that they are sufficient for a diagnosis. The siblings of such a child may want to know the likely recurrence rate when they have their children.
In a landmark study that analyzed the DNA of more than 35,000 people from around the world, the NIH-funded international Autism Sequencing Consortium (ASC) identified variants in 102 genes associated with increased risk of developing ASD, up from 65 identified previously. Of the 102 genes, 60 had not been previously linked to ASD, and 53 appeared to be primarily connected to ASD as opposed to other types of intellectual disability or developmental delay.
While common genetic variants collectively are known to contribute substantially to ASD, rare variants have been recognized individually as more major contributors to a person’s risk of developing ASD. The challenge was how to find such rare variants—whether inherited or newly arising.
The ASC assembled a vast trove of data from DNA samples over the last decade, with full consent from thousands of people with and without ASD, including unaffected siblings and parents.
The researchers knew from previous work that up to half of the people with ASD also have an intellectual disability or developmental delay. Many of the associated genes overlap, meaning they play roles in both outcomes. So, in one set of analyses, the team compared the list to the results of another genetic study of people diagnosed with developmental delays, including problems with learning or gross motor skills such as delayed walking. The detailed comparison allowed them to discern genes that are more associated with features of ASD, as opposed to those that are more specific to these developmental delays. It turns out that 49 of the 102 autism-associated genes were altered more often in people with a developmental delay than in those diagnosed with ASD. The other 53 were altered more often in ASD, suggesting that they may be more closely linked to this condition’s unique features.
Further studies also showed that people who carried alterations in genes found predominantly in ASD also had better intellectual function. They also were more likely to have learned to walk without a developmental delay.
The 102 new genes fell primarily into one of two categories. Many play a role in the brain’s neural connections. The rest are involved primarily in switching other genes on and off in brain development. Interestingly, they are expressed both in excitatory neurons, which are active in sending signals in the brain, and in inhibitory neurons that squelch such activity. Many of these genes are also commonly expressed in the brain’s cerebral cortex, the outermost part of the brain that is responsible for many complex behaviours.
These findings underscore that ASD truly does exist on a spectrum. Indeed, there are many molecular paths to this disorder.
Temple Grandin and most experts on autism think of autistic traits as being on a continuum. The more traits you had on both sides, the more you concentrated the genetics. Having a little bit of the traits gave you an advantage, but if you had too much, you ended up with very severe autism.” She warned that efforts to eradicate autism from the gene pool could put humankind’s future at risk by purging the same qualities that had advanced culture, science, and technological innovation for millennia.
In recent years, researchers have determined that most cases of autism are not rooted in rare de novo mutations but in very old genes that are shared widely in the general population while being concentrated more in certain families than others. Whatever autism is, it is not a unique product of modern civilization. It is a strange gift from our deep past, passed down through millions of years of evolution.
2. Infections and smoking. Some researchers also proposed that environmental factors can contribute indirectly to the development of AS. Viral or bacterial infection and smoking during pregnancy particularly increase the risk factor, although no concrete evidence supporting these views was found.
3. Difficult Pregnancy or Birth. In Lorna Wing’s (1981) original paper that first used the term Asperger’s syndrome, she noted that some of her cases had a history of pre-, peri-, and post-natal conditions that could have caused cerebral dysfunction. Her original observation has been confirmed by subsequent studies. Pregnancy complications have been identified in 31% of children with AS, and peri-natal or birth complications in about 60%. However, no single complication during pregnancy or birth has been consistently identified as being associated with the later development of AS. It is also not known if it was an already existing impairment of fetal development that subsequently affected obstetric events, with a difficult birth then increasing the degree of expression.
4. Other pregnancy factors. There does seem to be a greater incidence of babies who are small for gestational age and marginally older mothers when the child was born. More children with AS are born prematurely (36 weeks or less) or post-maturely (42 weeks or more). It is possible that factors that affect brain development during pregnancy and birth could affect the ‘social brain’ and contribute to the development of Asperger’s syndrome.
5. Brain and head circumference. For at least one in four children with AS, their brain and head circumference grew at a faster rate than would be expected in the first few months of being born. The children developed macrocephalus or an unusually large head and brain. There may be two categories of macrocephaly, one starting at birth and one that shows a rapid increase in head size during early pregnancy. This slows so that typical children usually catch up and head size difference may not be so conspicuous at age 5.
6. Neurotransmitter levels. An important causal factor behind the development of AS might be the altered level of neurotransmitters. In AS patients, higher levels of N-acetyl aspartate/Choline (precursor of acetylcholine) intake and increased dopamine levels were reported, suggesting an overall altered dopaminergic neurotransmitter composition in major areas of the brain. Intranasal injection of oxytocin, a neuropeptide, was shown to improve facial emotion recognition abilities in AS patients.
7. Why is autism so much more common in boys?
The ratio of males to females is about four to one. Girls with Asperger’s may be more difficult to recognize due to coping and camouflaging mechanisms, which can also be used by some boys. One of the coping mechanisms is to learn how to act in a social setting. The clinician perceives someone who appears able to develop a reciprocal conversation and use appropriate affect and gestures during the interaction. However, further investigation and observation at school may determine that the child adopts a social role and script, basing her persona on the characteristics of someone who would be reasonably socially skilled in the situation, and using intellectual abilities rather than intuition to determine what to say or do. An example of a camouflaging strategy is to conceal confusion when playing with peers by politely declining invitations to join in until sure of what to do, so as not to make a conspicuous social error. The strategy is to wait, observe carefully, and only participate when sure what to do by imitating what the children have done previously. If the rules or nature of the game suddenly change, the child is lost.
Girls with AS can develop the ability to ‘disappear’ in a large group, being on the periphery of social interaction – ‘on the outside looking in”. There can be other strategies to avoid active participation in class proceedings, such as being well-behaved and polite, thus being left alone by teachers and peers; or tactics to passively avoid cooperation and social inclusion at school and at home, as described in a condition known as Pathological Demand Avoidance.
A girl with AS is less likely to be ‘fickle’ or ‘bitchy’ in friendships in comparison to other girls and is more likely than boys to develop a close friendship with someone who demonstrates a maternal attachment to this socially naive but ‘safe’ girl. The characteristics reduce the likelihood of being identified as having one of the main diagnostic criteria for AS, namely a failure to develop peer relationships. With girls, it is not a failure but a qualitative difference in this ability. The girl’s problems with social understanding may only become conspicuous when her friend and mentor move to another school.
The language and cognitive profile of girls with AS may be the same as those of boys, but the special interests may not be as idiosyncratic or eccentric as can occur with some boys. Adults may consider there is nothing unusual about a girl who has an interest in horses, but the problem may be the intensity and dominance of the interest in her daily life: the girl may have moved her mattress into the stable so that she can sleep next to the horse. If her interest is dolls, she may have over 50 Barbie dolls arranged in alphabetical order, but she would rarely include other girls in her doll play. In conversation, boys may sound like ‘little professors’ with an advanced vocabulary and are able to provide many interesting (or boring) facts. Girls with AS can sound like ‘little philosophers’, with an ability to think deeply about social situations. From an early age, girls with AS have applied their cognitive skills to analyze social interactions and are more likely than boys with AS to discuss the inconsistencies in social conventions and their thoughts on social events.
The motor coordination problems of girls may not be so conspicuous in the playground, and they are less likely to have developed conduct problems that can prompt a referral for a diagnostic assessment for a boy. These parents, teachers, and clinicians may fail to see any conspicuous characteristics of AS in females.
In actual clinical practice, an astute clinician may find that the ratio of men to women adults is as low as 2 to 1. With increasing maturity, adults are prepared to get help, especially when there have been long-term and unresolved problems with emotions, employment, and relationships. Another pathway is when a woman has a child with AS and recognizes that she has a similar character.
One reason why the prevalence of Asperger’s Syndrome in girls and women is so low in comparison to boys and men may be the fundamental lack of awareness of what Asperger’s Syndrome “looks like” in females. Traditional frameworks may indicate that the female with Asperger’s Syndrome is just shy, quiet, and perfect at school so her parents must be exaggerating, tomboyish, moody, overly competitive, aloof, Gothic, depressed, anxious, or a perfectionist.
Research into fetal testosterone examines its effects on brain development and postnatal behaviour. Cambridge has analyzed the effects of prenatal testosterone levels, produced by the fetus and measured via amniocentesis during the first trimester of pregnancy, on autistic behaviour. Fetal testosterone shapes brain development to alter an individual’s cognitive profile by binding to androgen receptors in the brain, the amygdala is one region that is rich in such receptors. Cambridge researchers have shown that higher prenatal testosterone levels are associated with reduced social skills but superior attention to detail in infants.
