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Is autism caused by genetics?

Is autism caused by genetics?



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Is autism and Asperger's syndrome caused by genetics or some other factor such as the environment?

I am aware about the Neanderthal Theory of autism, Asperger and ADHD, but am not interested in this due to it appearing too broad and to me seems based off of opinions like preferring the cold to the heat which is not always the case, a the term "lack of social life" seem's very broad and not clear nor specific in the aspects of socializing that they are not good with. The aspect of having big brains is also very broad and does not cover in any detail about what it means by that, however if it means intelligence then this is a development from back when we needed to hunt for food as we started to create things and fleeing particular pray on sight became instinct. The section about being meat eaters does not conclude anything as many autistic people are vegans the same as neurotypicals so does not lead us anywhere. The section about woman being more submissive sexually is also not conclusive as most autistic people are asexual so there is no real dominance by both genders as most do not even partake in sexual activities. The graphs included are also questionable as they all seem to be in favor for aspies as they score higher on everything which i would say for things like the chances of having OCD they would be very much correct as the chances of having this when on the spectrum is 40 times more likely. A lack of organization is mentioned which to me does not seem right i feel that we over plan and organize. These category's specified do not cover everyone on the spectrum so therefore is not conclusive.


In light of a recent question in MedicalSciences.SE, I thought I would update this answer to include some information from my answer there.

Autism spectrum disorder (ASD) now affects one in 68 births in the United States and is the fastest growing neurodevelopmental disability worldwide (Edmiston, et al. 2017) [free access paper with links to cited papers].

Alarmingly, for the majority of cases, the causes of ASD are largely unknown, but it is becoming increasingly accepted that ASD is no longer defined simply as a behavioral disorder, but rather as a highly complex and heterogeneous biological disorder (Edmiston, et al. 2017).

With information available, the genetic and environmental causes of Autism is open to speculation and interpretation.

The NHS webpage on Autism states (Emphasis mine)

Most researchers believe that certain genes a child inherits from their parents could make them more vulnerable to developing ASD.

Cases of ASD have been known to run in families. For example, younger siblings of children with ASD can also develop the condition, and it's common for identical twins to both develop ASD.

No specific genes linked to ASD have been identified, but it may be a presenting feature of some rare genetic syndromes, including Fragile X syndrome, Williams syndrome and Angelman syndrome.

On environmental causes the NHS say that

Some researchers believe that a person born with a genetic vulnerability to ASD only develops the condition if they're exposed to a specific environmental trigger.

Possible triggers include being born prematurely (before 35 weeks of pregnancy), or being exposed in the womb to alcohol or to certain medication, such as sodium valproate (sometimes used to treat epilepsy during pregnancy).

No conclusive evidence has been found linking pollution or maternal infections in pregnancy with an increased risk of ASD.

Research Autism has some referenced information on leading research into the causes of Autism from the Medical Research Council, National Autistic Society and the Autism Society of America; and the crux of the matter from what is said here is that the causes are still being investigated and

There is no known single cause for autism, but it is generally accepted that it is caused by abnormalities in brain structure or function

The site also provides a list of publications on the possible causes of Autism

There has been research into autoimmune disorders causing ASD.

Edmiston, et al. (2017) stated (emphasis mine):

there are likely multiple, biologically defined subgroups within the ASD spectrum(3-7). Specifically, there is growing evidence that supports maternal immune dysfunction may underlie the behavioral abnormalities observed in a subset of children affected with the disorder(8). Several immunologic risk factors have been described including: genetic associations with immune-related genes(9-16), family history of autoimmune disease(15, 17-21), maternal inflammation and infection during pregnancy(22-27), and altered immune responses in the children, and are associated with increased impairments in core and associated features of ASD(28). More specific to this review, maternal anti-brain autoantibodies, which are thought to access the fetal compartment during gestation, have been identified as one risk factor for developing ASD and are proposed to contribute to early neurodevelopmental perturbations in the developing fetus(29-31).

References

  1. Lord C, Risi S, Lambrecht L, Cook EH, Leventhal BL, DiLavore PC, et al. The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism. Journal of autism and developmental disorders. 2000;30:205-223.
  2. Newschaffer CJ, Croen La, Daniels J, Giarelli E, Grether JK, Levy SE, et al. The epidemiology of autism spectrum disorders. Annual review of public health. 2007;28:235-258.
  3. Snow AV, Lecavalier L, Houts C. The structure of the Autism Diagnostic Interview-Revised: diagnostic and phenotypic implications. Journal of child psychology and psychiatry, and allied disciplines. 2009;50:734-742.
  4. Ousley O, Cermak T. Autism spectrum disorder: Defining dimensions and subgroups. Current Developmental Disorders Reports. 2013;1:20-28.
  5. McDougle CJ, Landino SM, Vahabzadeh A, O'Rourke J, Zurcher NR, Finger BC, et al. Toward an immune-mediated subtype of autism spectrum disorder. Brain Research. 2015;1617:72-92.
  6. Onore C, Careaga M, Ashwood P. The role of immune dysfunction in the pathophysiology of autism. Brain, Behavior, and Immunity. 2012;26:383-392.
  7. Warren RP, Singh VK, Cole P, Odell JD, Pingree CB, Warren WL, et al. Increased frequency of the null allele at the complement C4b locus in autism. Clinical & Experimental Immunology. 1991;83:438-440.
  8. Warren RP, Odell JD, Warren WL, Burger RA, Maciulis A, Daniels WW, et al. Strong association of the third hypervariable region of HLA-DRβ1 with autism. Journal of Neuroimmunology. 1996;67:97-102.
  9. Torres AR, Sweeten TL, Cutler A, Bedke BJ, Fillmore M, Stubbs EG, et al. The association and linkage of the HLA-A2 class I allele with autism. Human immunology. 2006;67:346-351.
  10. Campbell DB, Li C, Sutcliffe JS, Persico AM, Levitt P. Genetic evidence implicating multiple genes in the MET receptor tyrosine kinase pathway in autism spectrum disorder. Autism Research. 2008;1:159-168.
  11. Thanseem I, Nakamura K, Miyachi T, Toyota T, Yamada S, Tsujii M, et al. Further evidence for the role of MET in autism susceptibility. Neuroscience Research. 2010;68:137-141.
  12. Mostafa GA, Shehab AA. The link of C4B null allele to autism and to a family history of autoimmunity in Egyptian autistic children. Journal of Neuroimmunology. 2010;223:115-119.
  13. Jung JY, Kohane IS, Wall DP. Identification of autoimmune gene signatures in autism. Translational psychiatry. 2011;1:e63-e63.
  14. Torres AR, Westover JB, Gibbons C, Johnson RC, Ward DC. Activating killer-cell immunoglobulin-like receptors (KIR) and their cognate HLA ligands are significantly increased in autism. Brain, behavior, and immunity. 2012;26:1122-1127.
  15. Comi AM, Zimmerman AW, Frye VH, Law PA, Peeden JN. Familial Clustering of Autoimmune Disorders and Evaluation of Medical Risk Factors in Autism. Journal of Child Neurology. 1999;14:388-394.
  16. Atladóttir HO, Pedersen MG, Thorsen P, Mortensen PB, Deleuran B, Eaton WW, et al. Association of family history of autoimmune diseases and autism spectrum disorders. Pediatrics. 2009;124:687-694.
  17. Vinet É, Pineau CA, Clarke AE, Scott S, Fombonne É, Joseph L, et al. Increased Risk of Autism Spectrum Disorders in Children Born to Women With Systemic Lupus Erythematosus: Results From a Large Population-Based Cohort. Arthritis & rheumatology (Hoboken, NJ) 2015;67:3201-3208.
  18. Wu S, Ding Y, Wu F, Li R, Xie G, Hou J, et al. Family history of autoimmune diseases is associated with an increased risk of autism in children: A systematic review and meta-analysis. Neuroscience and biobehavioral reviews. 2015;55:322-332.
  19. Chen S-W, Zhong X-S, Jiang L-N, Zheng X-Y, Xiong Y-Q, Ma S-J, et al. Maternal autoimmune diseases and the risk of autism spectrum disorders in offspring: A systematic review and meta-analysis. Behavioural brain research. 2016;296:61-69.
  20. Chess S. Autism in children with congenital rubella. Journal of autism and childhood schizophrenia. 1971;1:33-47.
  21. Meyer U, Nyffeler M, Engler A, Urwyler A, Schedlowski M, Knuesel I, et al. The time of prenatal immune challenge determines the specificity of inflammation-mediated brain and behavioral pathology. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2006;26:4752-4762.
  22. Smith SEP, Li J, Garbett K, Mirnics K, Patterson PH. Maternal Immune Activation Alters Fetal Brain Development through Interleukin-6. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2007;27:10695-10702.
  23. Atladóttir HÓ, Thorsen P, Østergaard L, Schendel DE, Lemcke S, Abdallah M, et al. Maternal Infection Requiring Hospitalization During Pregnancy and Autism Spectrum Disorders. Journal of Autism and Developmental Disorders. 2010;40:1423-1430.
  24. Patterson PH. Maternal infection and immune involvement in autism. Trends in Molecular Medicine. 2011;17:389-394.
  25. Garay PA, Hsiao EY, Patterson PH, McAllister AK. Brain, Behavior, and Immunity Maternal immune activation causes age- and region-specific changes in brain cytokines in offspring throughout development. 2012
  26. Ashwood P, Van de Water J. Is autism an autoimmune disease? Autoimmunity reviews. 2004;3:557-562.
  27. Braunschweig D, Van de Water J. Maternal autoantibodies in autism. Archives of neurology. 2012;69:693-699.
  28. Fox E, Amaral D, Van de Water J. Maternal and fetal antibrain antibodies in development and disease. Developmental Neurobiology. 2012;72:1327-1334.
  29. Fox-Edmiston E, Van De Water J. Maternal Anti-Fetal Brain IgG Autoantibodies and Autism Spectrum Disorder: Current Knowledge and its Implications for Potential Therapeutics. CNS Drugs. 2015;29:715-724.

In conclusion, they pointed out that Maternal autoantibody related (MAR) ASD:

has been noted by numerous researchers describing the presence of maternal autoantibodies reactive to fetal brain proteins in a subset of mothers of children with ASD. Further, there is now an abundance of evidence supporting their deleterious role in neurodevelopment. For the most part, these studies have described similar experimental outcomes and, given the clinical and biological heterogeneity of ASD, there likely exists a complex relationship between the presence of maternal anti-fetal brain antibodies and developmental trajectory of exposed offspring. It is still unclear how and when these maternal autoantibodies arise, but studies currently underway may provide increased insight into their ontogeny.

References

Edmiston, E., Ashwood, P., & Van de Water, J. (2017). Autoimmunity, autoantibodies, and autism spectrum disorder. Biological psychiatry, 81(5), 383-390. Pubmed Central: PMC5373490


Since the 1970s, researchers have found out and known that genes make a contribution to the pervasive developmental disorder or autism when two identical twins have shared a similar condition.

As the world progresses, scientists have found out the variety of genetic changes in the DNA that contribute to the autism spectrum. However, genetics cannot be solely accounted for the risks of developing signs for autism spectrum. There are various other factors involved as well,

  • A child being born to older parents
  • Low birth weight and premature infants
  • Hormonal and metabolic imbalances
  • Fetal exposures to the medications such as valproic acid or thalidomide
  • Exposure to heavy metals and environmental toxins
  • Fragile X syndrome and other inherited disorders
  • Having an immediate family member with autism

Working with Arizona Centers for Comprehensive Education and Life Skills, I have realized children or adults with pervasive spectrum need distinctive care and affection.


Seven Science-Based Facts on Which Researchers Agree

While it is possible to find someone out there who will disagree about virtually any statement regarding autism, the vast majority of experts do agree on the following seven points. While these points don't necessarily provide a clear path to prevention or cure, they do help point the way.

There Is More Than One "Autism"

About 25% of autistic people have digestive issues 25% have seizure disorders many have sleep problems. Recent findings suggest that the many different symptoms may actually indicate many different causes -- and thus many different "autisms." A massive study now underway at UC Davis's M.I.N.D. Institute is in the process of separating out different autistic phenotypes with the hope that this information will speed better understanding of causes and treatments.

Autism Has a Genetic Component

Autism is hereditary, in that children with autistic people in their family are more likely than other children to be autistic. Researchers are well on the way to finding genes that relate to autism -- but the jury is still out regarding exactly how such genes might function to create autistic symptoms. Sophia Colamarino, Science Program Director at Cure Autism Now, explains, "We’re talking about genes because they allow us to understand the biological origins of the problem."

There Is a Relationship Between Autism and Brain Structure

Recent brain studies show that autistic brains grow at an unusual rate between the ages one and two and then slow again to a normal rate of growth. Some imaging studies suggest that certain areas of the brain are larger than is typical. Research is ongoing to determine whether these differences in brain structure cause autism, are caused by autism, or are comorbid with autism and caused by something else.

There Is a Relationship Between Autism and Brain Activity

Recent brain imaging studies show that autistic people and typically developing people do not use their brains in the same way. Autistic people do not use their brains to "daydream" in the same way as most people, nor do they process information about faces in the same way. So far, while we know that this information is true, we don't know what causes these differences -- or whether these differences somehow cause autistic symptoms.

There Is a Relationship Between Autism and Brain Chemicals

Chemicals in the brain transmit signals which allow the brain to function normally. Sophia Colamarino explains: "Nerve cells communicate using electrochemical signals there is evidence from many different domains that the ability of the brain to transfer information may be defective." An understanding of which transmitters are problematic may lead to effective treatments.

Genes Probably Interact With Environmental Factors

It is likely that genetics and environmental factors interact to cause autism. As yet, there is no proof of which environmental or genetic factors are to blame. Says Dr. Croen, autism "You need some kind of genetic susceptibility then you have to be exposed to something which is elusive at the moment. This would be the impetus that sends you into autism."

No One Factor Causes Autism

It is unlikely that any single factor—vaccines, foods, or environmental toxins—is the cause of the steep rise in autism diagnoses. "To find clues about the cause," says Dr. Croen, "we have to do really large studies to look at different configurations of co-morbidities… see what’s unique about each separate group." New research will be addressing the questions "How do these circles overlap? What is the common thread?"


What Causes Autism Spectrum Disorder?

Genetic factors play a big role in causing autism spectrum disorder, but researchers suspect environment is also involved.

Autism spectrum disorder (ASD) is a neurodevelopmental condition — a group of conditions involving brain differences that can affect behavior, memory, communication, and learning.

Autism is complex, and no two autistic people are the same. Because of this, researchers believe there are probably many causes of autism, including genetic and environmental factors.

So far, some evidence suggests that changes (aka mutations) in a person’s genes could cause autism. Other research suggests that a combination of genes and environment may contribute to the causes.

Many autistic people view autism as part of their identity — not as a condition to be treated or prevented. So, some people are now saying that research on its causes isn’t the best use of resources, since some of this is centered around prevention.

Some autistic people and advocates suggest research and resources that support autistic people are much more helpful.

Many experts believe genes play the biggest role in causing autism. A 2019 study estimated that about 80% of autistic people have it due to genetics.

Research has found more than 800 genes linked to autism. Recently, researchers reported that more than 100 genes are implicated in developing autism.

While research suggests that many autistic people have small mutations in a lot of their genes, it’s not always clear how big of a role these mutations play.

In fact, many autistic people have different mutations, and some don’t show the genetic changes that are often connected to autism. This means that different mutations probably play different roles in causing autism.

For example, some mutations or combinations of mutations could:

  • play a role in causing certain behaviors
  • contribute to whether someone needs minimal or significant support
  • increase a person’s chances of having autism

Other genetic factors that could increase someone’s chances of developing autism include:

  • assigned male at birth
  • having an autistic sibling
  • a chromosomal condition like fragile X syndrome

Because we tend to have more control over environmental factors, researchers have put effort into studying environmental causes of autism.

So far, research suggests that the most influential factors that increase a person’s chances of developing autism are related to what happens before and during birth, like if:

  • the fetus is exposed to air pollution or certain pesticides before birth
  • the pregnant parent has diabetes or another immune system disorder
  • the baby is born before 36 weeks old
  • there were birth complications like the baby was breech, in fetal distress, or had a low birth weight
  • there were any issues during birth that caused a limited amount of oxygen to the baby’s brain

These factors likely don’t cause autism by themselves. For instance, many babies are born before 36 weeks, with and without autism.

Researchers have also looked into other biological factors connected to autism. These factors are involved with:

Some research links certain immune system issues with autism.

The same research suggests that some infections during pregnancy could increase the child’s likelihood of having autism. Several other immune issues may also increase likelihood, including:

  • problems with how the immune system works
  • inflammation
  • developing antibodies to a condition they haven’t been exposed to

Another possible factor linked to autism? How well an autistic person’s mitochondria (the “powerhouse” of the cell) work. Mitochondria create the majority of a cell’s energy and are an important part of metabolism, among other things.

Recent research has found that there may be a link between mitochondrial function and autism.

Additionally, scientists suggest that mitochondria are also affected by some of the same environmental factors that can increase the chances of someone being diagnosed with autism.

Other factors that may play a role in someone’s chances of developing ASD include:

  • the frontal cortex of the baby’s brain overgrows shortly after birth
  • the baby is male (autism is 4 times more common in boys than girls)
  • advanced paternal age

An autism diagnosis may also be more likely if during pregnancy, the parent:

  • had hypertension or diabetes
  • experienced an antepartum hemorrhage in the third trimester or postpartum hemorrhage
  • has given birth to more than 4 children
  • had preeclampsia

Some people believe that vaccines cause autism. This isn’t true.

According to many organizations, including the Centers for Disease Control and Prevention (CDC) , there’s no evidence that vaccines cause autism.

This belief comes from a study published in the British medical journal, Lancet, in 1998. The study concluded that the measles, mumps, and rubella (MMR) vaccine caused autism.

The study wasn’t properly conducted, and it was later retracted and disproven. But it gained a lot of publicity, and some people still believe the false findings are true.

Other factors, like smoking during pregnancy, exposure to mercury, or fertility treatments are also believed to cause autism. None of these causes have been proven.

Autism is diagnosed by a medical professional, often a pediatrician or specialist.

According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), an autistic person must have both social and behavioral patterns that meet the criteria for autism spectrum disorder.

Someone might receive an autism diagnosis at 18 months or younger, but it’s more common to get diagnosed around 2 years old.

Still, some people don’t get a diagnosis until much older or until adulthood.

When diagnosing ASD, clinicians may look for patterns in communication like:

  • difficulty with back-and-forth conversation
  • differences in nonverbal communication like facial expressions or body language
  • difficulty adjusting behavior to different social settings

A doctor may also look at these behavioral patterns when screening for autism:

  • specific movements, actions, or gestures
  • strong attachment to routine
  • specific, strong interests
  • differences in sensory processing

Many autistic people see autism as an identity, not as a condition to be treated. But if you’re experiencing challenges related to being autistic, there are many ways to find support, depending on your needs.

If you’re a parent of an autistic child, you can get some tips for how to support your child here. And if you’re an autistic adult, you can learn more about strategies, support, and therapies here.

When learning what kinds of resources your autistic child needs, it can help to research your options and talk to doctors. Deciding what’s best for your child will depend on the level of support they need and what’s available to you.

While there’s no single way to support autistic people, professionals often agree that the earlier you can connect with support services, the better. Many forms of support — especially for autistic children — can help them feel safe and understood.

Autism is complex. While genetics may be a key factor in causing autism, it’s likely that a person’s environment and other factors also play a role.

Researchers have found more than 800 genes linked to autism. While we still don’t know as much about environmental or biological factors, researchers have made progress.

No matter what causes autism, there’s plenty of opportunities for autistic people to live well and find the support that works for them.


Genes and ASD

Genes: Bits of DNA that carry instructions for "building" your body.

Chromosomes: Packages of DNA and genes in the cells of the body.

A great deal of evidence supports the idea that genes are one of the main causes of or a major contributor to ASD. More than 100 genes on different chromosomes may be involved in causing ASD, to different degrees. 3,4

Many people with autism have slight changes, called mutations, in many of these genes. However, the link between genetic mutations and autism is complex:

  • Most people with autism have different mutations and combinations of mutations. Not everyone with autism has changes in every gene that scientists have linked to ASD.
  • Many people without autism or autism symptoms also have some of these genetic mutations that scientists have linked to autism.

This evidence means that different genetic mutations probably play different roles in ASD. For example, certain mutations or combinations of mutations might:


Evidence for converging molecular pathways

Several recent studies have suggested that in addition to convergent brain pathways, that there may as well be convergence at the level of molecular mechanisms in ASD. One class of such studies has asked whether putative ASD susceptibility genes are enriched in members for specific molecular or biological processes more than expected by chance. The value of this approach depends on the level of experimental support for the specific genes tested and the degree to which current pathway annotations represent reality [25, 68]. For genes identified within CNV this can be particularly problematic, as most known pathological CNV contain more than one gene and it is not expected that all genes within the CNV contribute to ASD, potentially increasing noise in this analysis. One recent study [69] reduced such background by using a new phenotype-driven method to group genes within high confidence de novo CNV [34, 69], identifying significant enrichment for several categories of genes, including axon outgrowth, synaptogenesis, cell-cell adhesion, GTPase signaling, and the actin cytoskeleton. These results replicate and extend earlier composite pathway analysis of putative ASD susceptibility genes compiled from the literature [68], and CNV pathway analysis in the Autism Genetic Resource Exchange (AGRE) and other cohorts [32, 36]. Still, these studies place ASD genes within a multiplicity of pathways, several of which are broad and do not necessarily demonstrate convergence on final common molecular processes in individuals.

In this regard, two recent studies use quite different systems biology approaches to provide a new perspective on the concept of molecular convergence. The first, an analysis of gene expression in post-mortem autism brain, provides the strong evidence for a shared set of molecular alterations in a majority of cases of ASD. This included disruption of the normal gene expression pattern that differentiates frontal and temporal lobes (consistent with an early developmental patterning defect), and two groups of genes dysregulated in ASD brains: one related to neuronal function, and the other to immune/inflammatory responses [49]. The neuronal function genes were enriched in genetic association signals, providing evidence that these changes were causal, rather than the consequence of the disease [49], while the immune/inflammatory changes did not show a strong genetic signal, implicating environmental or epigenetic factors instead. It is also notable that the several of the same biological pathways identified in this gene expression study overlapped with the pathway analysis of CNV described above. This analysis of post-mortem autism brain also showed down-regulation of several markers of GABAergic interneurons, suggesting potential inhibitory interneuron dysfunction. These results provide the first strong evidence for both a shared genetic and an environmental/epigenetic basis for ASD and the presence of an early developmental patterning defect. It is tempting to speculate that the abnormalities in cortical patterning and interneuron function provide a molecular basis for cortical-cortical and cortical-fugal disconnection, linking molecular abnormalities with anatomical, physiological and imaging findings.

The second study on molecular convergence in ASD identified protein interactors of known ASD or ASD-associated genes [70]. This interactome revealed several novel interactions, including between two ASD candidate genes, Shank3 and TSC1. The biological pathways identified in this study include synapse, cytoskeleton, and GTPase signaling, demonstrating a remarkable overlap with those identified by the gene expression and CNV pathway studies discussed above. This study differs from other genome-wide studies (such as mRNA expression) as it begins with known ASD genes and asks about their relationships. So although it is “ –-omic” in nature [71], it is not quite as unbiased as methods that survey the genome more agnostically. Despite the significant heterogeneity in ASD, these diverse studies identify several common areas of molecular convergence in ASD. Understanding how these pathways relate to individual differences now becomes an important research priority.


Is autism caused by genetics? - Psychology

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July 5th, 2020

Neuropsychological Research

PSYCHOLOGICAL ASPECTS OF AUTISM SPECTRUM DISORDER

1. Introduction

Autism spectrum disorder (ASD) is a pervasive developmental disorder that has both fascinated and frustrated scientific and clinical researchers. It is a major mental health, educational and social medical challenge. Autism has epidemic proportions worldwide. The Centre for Disease Control and Prevention states that autism spectrum disorder occurs in about 1 in 54 eight year old children in the USA (Maenner et al., 2016). Unfortunately, in Macedonia, there is no statistical data about the prevalence of this condition. The etiology and neuropsychological basis of this complex disorder still remains uknown. The perspective of a psychological model of autism is that the social and communicative impairments reflect fundamental difficulties in understanding other people as mental beings &ndash the so-called &ldquotheory of mind&rdquo hypothesis of autism (Tager-Flusberg, 1999). It is a life-long disorder that has a substantial effect on the individuals, their family, and society as well. Autism is a complex neurodevelopmental disorder encompassing severe abnormalities in reciprocal social interaction, verbal and nonverbal communication, accompanied by restricted and repetitive behaviours and interests. These behavioural symptoms are present in very early childhood, before the age of 3 years. There is much variability in the disorder in terms of intellectual functioning, language ability, and severity of behavioural symptoms, (APA, 2013). This creates psychological and social impacts on affected individual and creates problems for parents in dealing with the children with ASD. This disorder is a major economic burden for all societies in the world.
It is a spectral disorder where some individuals with ASD are mildly affected by their symptoms some are moderate impaired, whereas the others are profoundly affected. There is major heterogeneity in ASD, and the range of ASD symptoms can be classified into broad categories of core symptoms and secondary symptoms. Secondary symptoms can include conditions such as intellectual impairment, which occurs in approximately 70% of patients with ASD, aggressiveness toward others, self-injury, eating disturbances, sleeping disorders, and seizures. Clinical characteristics are changeable throughout the lifespan. For example, language difficulties and hyperactivity that is often seen in younger children can shift to relational problems, mood dysregulation, and hypo-activity in adolescence and young adulthood. Diagnosis of ASD can be challenging, but progress has been made in refining diagnostic processes that can be addressed over the lifespan (Elder et al., 2017).
Children with ASD are more exposed to social stigmatisation and social rejection due to a lot of prejudice. Apart from stigma, Macedonia has a lack of treatment facilities, lack of trained child special educators and psychologists, lack of diagnostic procedures, lack of awareness among people, poor attention and poor resources from the government and a lack of proper welfare facilities, education facilities and rehabilitation services for children with ASD. Social institutions at the local level are not capable of ensuring that people with autism can remain in their area of residence and be provided with adequate educational and social services. The lack of statistical data on people with a disability hampers an evaluation of whether all people with any given disability are socially jeopardised and if they are able to access their rights in the field of social care. The Law on social protection established measures and services in the field of social protection and social care through social prevention, de-institutional care, protection and the right for social support (Trajkovski, 2008).
People identified with autism spectrum disorders have high frequencies of one or more co-occurring non-ASD developmental, neurologic, psychiatric, metabolic, immune, gastrointestinal and possibly causative medical diagnoses. Seizures, disturbed sleep and painful gastrointestinal disorders are some of the health conditions commonly associated with autism. Autism is frequently accompanied by mental health conditions including anxiety, depression, and ADHD. Medical conditions and consecutive pathological processes can negatively impact behavior, socialization, communication, cognitive function and sensory processing of individuals with autism. Accurate diagnosis and treatment often results in improved level of functioning and decreased severity of symptoms (Trajkovski, 2018).
Psychologists complete assessments of children with autism. The assessment can be related to diagnosis, cognition (IQ) or the way a child with autism thinks and sees the world. Psychologists have focused their efforts on the cognitive level of explanation in order to identify the underlying processes that might account for the various behavioural manifestations of the disorder. Historically, and in the interests of parsimony, the emphasis upon these theories has been to posit a single primary cognitive deficit that could explain the development of autism. Theories from three cognitive domains have dominated the field: theory of mind &ndash the ability to reason about the mental states of others executive control &ndash a set of abilities important for flexible behaviour in novel circumstances and central coherence &ndash the natural propensity to process information in context (Pellicano, 2007).
The purpose of this review article is to create an overview of current knowledge on the most prominent psychological factors that format and are formatted by the development of ASD. Also, the other goal is to explore diagnostics and treatment from a psychological perspective.

2. Psychologic functions in ASD

In the following pages, psychologic functions, which are altered in ASD, will be described such as attention, executive function, academic functioning, memory, emotions, and sensory processing.

2.1. Attention

Attention is a concept studied in cognitive psychology that refers to how we actively process specific information in our environment. Attention is a multi-dimensional construct that encompasses several components, including focusing, sustaining, and shifting operations, (Mirsky et al., 1999). Children with ASD do not usually have problems with sustained attention. They have problems with focusing attention, although their pattern is different from that of children with attention-deficit/hyperactivity disorder (ADHD). Those with ASD tend to &ldquomiss the forest for the trees&rdquo or over-focus attention on extraneous details while missing meaning. This difficulty has also been called impaired central coherence, (Happe and Frith, 1996). Children with ASD are more distracted by internal phenomena (e.g., special interests) than those with ADHD, whose attention is more typically diverted by external stimuli in the environment. Some children with ASD do exhibit classic ADHD symptoms of distractibility and hyperactivity (Ghaziuddin et al., 1992). Attentional abnormalities have long been documented in individuals with ASD using a variety of experimental paradigms and tasks. The predominant model of attention puts forward three critical components: alerting, orienting, and executive (Petersen and Posner, 2012). The alerting component of attention includes the ability to produce and maintain optimal vigilance and performance during tasks. The orienting component of attention includes the ability to prioritise sensory input by disengaging, shifting, and re-engaging attention to a modality or location. The executive component of attention includes resolving conflict among competing responses. Sensory issues and attentional issues are closely connected to each other.

2.2. Executive function

Executive function describes a set of cognitive processes and mental skills that help an individual to plan, monitor, and successfully execute their goals. These include attentional control, working memory, inhibition, and problem solving many of which are thought to originate in the brain&rsquos pre-frontal cortex. One of the most consistently replicated cognitive deficits in individuals with ASD, is executive dysfunction, (Ozonoff and Jensen, 1999). The executive function domain includes the many skills required to prepare for and execute complex behaviour, including planning, inhibition, organisation, self-monitoring, mental representation of tasks and goals, and cognitive flexibility and set shifting.
Executive attention has also been shown to be impaired in young people with ASD. School-aged children and adults with ASD demonstrate larger flanker effects, i.e., slower response when the flanking arrows are pointing in an incongruent direction from the central target arrow (Mutreja et al., 2015), though there are some negative findings as well (Geurts et al., 2008). Executive function is defined as the ability to regulate one&rsquos thoughts, emotions, and actions in order to achieve volitional goals (Zelazo et al., 2008). Executive function is one of the most studied cognitive constructs in ASD with more than 400 empirical articles since 1985 that have been covered across several comprehensive reviews (Wallace et al., 2016) and meta-analyses (Lai et al., 2016). This heavy investigation has been driven by long-standing clinical observations that individuals with ASD show executive function impairments. While intensive investigations have demonstrated that early executive function impairments are not causal of ASD, executive function skills can predict some forms of mentalising, repetitive behaviours, adaptive function skills, academic readiness, and challenging behaviours. In the following sections, we will review research in the three core components of executive functioning: updating, shifting, and inhibition, (Miyake and Friedman, 2012). Examination of more complex executive function tasks, like Tower tasks that tap into planning and organisation skills or Verbal Fluency tasks that tap into generativity skills, reveal impairments of a moderate effect and size in individuals with ASD compared to controls. Furthermore, performance in tasks assessing planning, appear to be significantly influenced by co-occurring ADHD symptoms, while this is not the case for tasks assessing generativity skills (Lai et al., 2016).

2.3. Academic functioning

It is very important to assess academic skills, even in younger children, for the purposes of educational decision making. Many children with ASD have precocious reading skills and can decode words at a higher level than others of the same age and functional ability. The first set of difficulties relates to the ability of students with autism to attend in traditional educational environments. These students have difficulty completing an activity from start to finish. Reading and other academic strengths can be used to compensate for weaknesses, as when a written schedule is provided to facilitate transitions or written directions are supplied to improve compliance. The good memory of children with ASD may mean that spelling lists and multiplication tables are learned more easily. Specific areas of weakness also exist, with the most consistently demonstrated one being reading comprehension. Whether communicating information about routines, academic content, or social expectations, teachers use verbal language. For many learners with autism, this strategy is ineffective. They are unable to process complex verbal information. They cannot understand abstract notions.
It is important that appropriate test batteries that assess both academic strengths and weaknesses be included in a comprehensive evaluation of a child and the learning patterns they suggest be interpreted in the feedback to parents and appropriate educational recommendations are made in the written report.
The performance profile seen in measures of academic function is consistent with that obtained from intellectual tests. Academic skills requiring primarily rote, mechanical, or procedural abilities are generally intact, while those relying upon more abstract, conceptual, or interpretive abilities are typically deficient. Some authors in the reading domain found that individuals with high-functioning autism performed as well as or better than normal controls matched on age and IQ on tests of single-word oral reading, non-word reading, and spelling (Minshew et al., 1994). These measures all require phonological decoding skills and thus indicate preserved or even advanced knowledge of grapheme&ndashphoneme correspondence rules in autism. In contrast, subjects with autism performed less well than controls on two measures of reading comprehension. This pattern, in its most extreme form, is named hyperlexia. It is used to describe individuals with word recognition skills that are significantly better than predicted by intellectual or educational level. Hyperlexia has been documented in individuals with autism by a number of researchers (Nation et al., 2006). The cognitive and social communication characteristics serve as the basis for the development of systematic instruction and the use of visually structured environments. Students with autism may have difficulty learning in distracting environments.

Memory refers to the processes that are used to acquire, store, retain, and later retrieve information. There are three major processes involved in memory: encoding, storage, and retrieval. Memory has been a focus for researchers in search of basic psychological factors that contribute to the development of ASD (Boucher et al., 2012). Non-declarative memory includes perceptual memory (automatic and unconscious memory) and procedural memory (conditioning, habit memory, the learning of sensorimotor or cognitive skills). Declarative memory is the explicit acquisition and maintenance of information over a longer time.
Non-declarative memory appears to be largely intact in individuals with ASD without ID, particularly when stimuli are non-social in nature. Tasks include implicit learning tasks, in which children are repeatedly exposed to a stimulus and learning is reflected in faster (and/or more accurate) responses over trials. Intact performance is observed in implicit motor sequence learning (Travers et al., 2010) and spatial context learning (Kourkoulou et al., 2011). However, there is some preliminary evidence of a slower adaptation of learning when the learning task biases individuals with ASD toward local features of a stimulus. Other non-declarative tasks that reveal intact performance in ASD include perceptual or conceptual priming for words, pictures, and music. However, fear conditioning tasks, in which participants are repeatedly exposed to a stimulus and learning is reflected in faster (and/or more accurate) response over trials, have revealed impairments in adults with ASD (Gaigg and Bowler, 2007).
Declarative memory research in ASD is characterised by a pattern of mixed findings of intact and impaired performance across tasks, moderated by cognitive ability. Recognition memory tasks involve the presentation of a list of stimuli (e.g. words, aurally or visually). Subsequently, participants are tested by being shown a group of stimuli (e.g. list of words) that were either part of the to-be-remembered group (targets) or not (foils). Performance has been reported as largely intact in individuals with ASD without ID for tests using nonsocial stimuli, such as lists of words, stories, and pictures of common objects. However, recognition memory may be impaired in verbal individuals with ASD and ID, and when face stimuli are used. Free recall tasks which require individuals to remember unrelated words revealed no impairments in individuals with ASD across age and immediate or delayed recall conditions however, control groups outperformed individuals with ASD when semantically related word lists were used, suggesting that non-ASD populations were able to make use of this higher-order category to support memory (Bowler et al., 2008).

2.5. Motor development

Motor development refers to the development of a child&rsquos bones, muscles and ability to move around and manipulate things in an environment. Motor development can be divided into two sections: gross motor development and fine motor development. Children with autism tend to also have motor difficulties. Early descriptions of these children suggest that they were graceful and skillful and had few signs of motor impairment. This was part of the puzzle relating to the origins of the disorder. Later systematic studies of motor performance in low-functioning cases uncovered clear signs of delayed or abnormal motor and sensorimotor development (Jones and Prior, 1985). One author found motor imitation problems in children with high-functioning autism and basic motor functioning problems or dyspraxia which were significant handicaps to imitation (Bennetto, 1999). Problems in producing gesture, either by imitation or spontaneously, may underlie the well-known failure of children with autism to use gesture to communicate like neuro-typical children. Motor dyspraxic and neurodevelopmental signs such as choreiform movements, gait abnormalities, balance problems, and impaired body imitation abilities are significant characteristics of autism (Goldstein et al., 2001).
Motor problems are showed to be slow in a substantial proportion of cases (DeMyer et al., 1981), although it is unknown whether neurologically impaired children with autism are different in other significant ways from those without measurable signs on these indices. Some authors compared children with autism with those who had language disorders and with controls on a neurological examination. They found motor problems across balance, coordination, fine, gross and oromotor functions (Noterdaeme et al., 2002). Using standardised tests of motor impairment and including children with Asperger&rsquos syndrome and higher-functioning autism as subjects (Ghaziuddin et al., 1994), it has been shown that both groups show signs of neuro-motor clumsiness across a range of motor systems. Their graphomotor scores, as ascertained from testing with standard visuomotor tests, remained an area of weakness in ability profiles from early to later ages. In the academic domain, although the higher IQ group had normal range scores in numeracy and literacy, their written expression was a notable weakness. Ongoing problems with written work in the school curriculum, which of course requires fine motor skills and effort (Manjiviona, 2003).
Research examining deficits in motor execution and motor planning was also presented and opens up avenues for further research. The use of magnetic resonance imaging, to establish abnormalities in neural underpinnings of motor control, is one possibility. Motor dysfunction of individuals with autism, poses concerns for parents and professionals. Delayed motor development will impact on physical activity participation and the development of daily living skills for individuals on the autistic spectrum. This clearly indicates the need for intervention studies to examine the effects of physical activity on the motor development of individuals with ASD.

2.6. Emotional processing

Emotional processing happens when an individual experiences an emotionally distressing event and is able to cope with those experiences over time to the extent that new experiences can occur (whether stressful or not) without a return to the previous distress. While individuals with ASD feel and express emotions, their emotional expressions are reduced in frequency and manifested in more ambiguous ways compared to those of typically developing individuals, as reflected across facial expressions, body postures, spontaneous language and prosody (Brewer et al., 2016). Individuals with ASD have difficulties recognising emotions in others from their facial and bodily expressions, and their prosody. Emotion processing difficulties appear to vary greatly across individuals and studies (Nuske et al., 2013), with more pronounced difficulties reported in tasks testing recognition of complex versus simple, intense versus subtle, and negative versus positive emotions.
Empathy is another area of weakness in ASD, although recent studies suggested that difficulties in this area are related to the cognitive dimension (understand what others are feeling) rather than the affective dimension (feeling concern in response to others&rsquo emotions) of empathy (Mazza et al., 2014). Recent work by (Schwenck et al., 2012) has pointed to a double dissociation, where individuals with ASD were selectively impaired in cognitive empathy, while those with conduct disorder were selectively impaired in affective empathy. Atypicalities in the emotion processing domain are more frequently reported in studies testing brain and physiological responses to emotional displays, compared to behavioural studies. Findings include atypical physiological arousal and reduced brain activity in emotion processing circuitries in response to emotional scenes, and emotional prosody. Emotion processing difficulties have been reported to increase with age, and to be associated with lower social skills as well as lower verbal and non-verbal cognitive functioning. It is still debated whether such abnormalities in ASD represent a primary deficit in emotion processing, a manifestation of social impairments (possibly involving social-motivational and social-cognitive factors), or the final outcome of multiple social and non-social abnormalities (Vivanti et al., 2019).

2.7. Problems with sensory processing

Sensory processing refers to the way the nervous system receives messages from the senses and turns them into responses. Through the senses, we learn about our environment as well as ourselves, creating memories that contain records of our history of sensory experiences. The presence of sensory disorders in children with autism is widely recognised nowadays. The range of such sensory dysfunctions is considerable and includes tactile, auditory, visual, olfactory and gustatory hyper or hypo sensitivity. Tactile hypersensitivity is evidenced by the aversion to wearing certain types of clothing, walking on grass or textured flooring or handling certain types of objects and materials. Some individuals show extreme anxiety in social situations because of their tactile hypersensitivity. A person with visual processing differences may have difficulties with bright or flashing lights, such as fluorescent lights. A restricted diet and refusal to eat particular foods is also common in children with autism. It is not always clear whether the refusal is related to the taste, smell or texture of the food or some combination of these characteristics.
In addition to hypersensitivity, some individuals show reduced sensitivity (hypоsensitivity) to pain, cold and sound, as well as a wide range of other sensory inputs. In contrast, other people with autism appear to be strongly attracted to certain types of stimuli to the extent that they can fixate on them and tend to maintain that stimulation through repetitive and compulsive behaviours. For example, some children crave deep pressure stimulation. There are individuals who are particularly attracted to scents and tend to smell everything. There are speculations that some children’s reading difficulties may be related to letters that appear wavy or completely missing. Some sensory problems may reflect the inability to coordinate or integrate sensor input from multiple sources or multiple sensing modalities. Children with this last type of problem may find it difficult to follow a conversation when there are background sounds or have visual stimulus problems when speaking. It is also speculated that sensory interference (synesthesia) may occur in some individuals if the person can see sounds or hear pictures. Finally, some sensory dysfunctions include the vestibular system that helps regulate balance and movement, and the proorption system that provides feedback from muscles, tendons, and ligaments on body posture (Huebner, 2001).

3. Diagnosis of ASD from a psychological perspective

The process of establishing an ASD diagnosis and linking to early intervention and support services is often a major challenge. The processes include: identifying diagnostic needs for ASD, ensuring accurate assessment by a trained professional, and opening up appropriate ASD child services that include complex individual, social and medical factors that are often difficult to manage from a logistical and financial perspective (Lappé et al., 2018). The list of experts which can make the diagnosis is long and it includes: paediatricians, neurologists, and psychologists. The expert making the diagnosis should have extensive experience working with the wide range of symptoms. To make a diagnosis of ASD, psychologists draw on a number of sources of information: patient interviews, observations of the patient&rsquos behaviour, tests of cognitive and language abilities, medical tests to rule out other conditions, interviews with parents, teachers or other adults who can answer questions about the patient&rsquos social, emotional and behavioural development. Psychologists, working in partnership with physicians, speech and language pathologists, and occupational therapists, can lead or contribute to multi-disciplinary diagnostic teams in clinical settings. Psychologists are skilled in diagnostic practices and the assessment of cognitive and behavioural functions. After the evaluation is complete, they often play important roles in treatment and case management, making referrals to community resources, setting up interventions in schools and homes, and providing various therapies for both children and families.

4. Treatment of ASD from a psychological perspective

Children with ASD benefit from interdisciplinary treatment teams made up of various experts from various fields. Those teams typically include physicians, special educators, speech therapists, occupational therapists, and psychologists. Several interventions have been developed to treat children with ASD. Some of the most common evidence based approaches include following: Applied Behaviour Analysis (ABA), Developmental Individual-Difference Relationship-Based model (DIR), and TEACCH. ABA is an intensive method that uses teaching techniques to increase helpful behaviours and reduce behaviours that are harmful or interfere with learning. ABA therapy has been shown to improve communication, social and vocational skills. In the DIR model, also known as floor-time therapy, parents and therapists follow the child&rsquos lead in playing together while also directing the child to engage in increasingly complex interactions. The TEACCH framework promotes engagement in activities, flexibility, independence and self-efficacy through strategies based on the learning strengths and difficulties of people with ASD. There are some other promising treatments such as: Reattach therapy, Sensory Integration Therapy and art and drama therapy. These interdisciplinary treatments can improve a variety of abilities required for daily life, for example, dressing, eating, and fine motor developments, which can assist somebody with ASD and manage their sensory overload (e.g.: sights, sounds, touch, etc.). The child should be evaluated by a professional trained in diagnosing and treating autism, so that he or she can recommend the most appropriate interventions. Such interventions can be administered by psychologists, as well as by special educators and board certified behaviour analysts. Psychologists also play an important role in helping children of all ages as well as adults with ASD manage specific challenges associated with the disorder (APA, 2019).

5. Conclusion

Autism spectrum disorder is probably the most misunderstood and puzzling of the neurodevelopmental conditions. This article focusses on the psychological aspects of ASD and diagnostics and treatment from a psychological perspective. While major advances have been made in the field, it is clear that more special education services are needed, together with timely and ongoing psychosocial support to parents of children with ASD. It is clear that ASD is a lifelong condition and families must learn to shift their focus from treatments to developing life-skills as their child grows into adulthood. They should not need to rely on possible misinformation on the internet. Effective communication between service providers and families is the key to building supportive relationships that can positively affect not only the individual with ASD but also the family over a lifetime.
Individuals with ASD possess strengths of character, unique skills, and untapped resources that should not be undervalued or unappreciated. The professional discussion of these qualities communicates a belief that individuals with ASD and their families can do more than simply survive. They can live enriched and fulfilling lives and they can be valued for what they can offer to society. Some individuals with ASD, particularly those with better language and intellectual skills, can live and work independently as adults. They should have support to access employment in their community. The degree of malleability of core and associated ASD features remains unclear, as treatment effects attained in research settings are not always replicated in community settings, and more research on the mechanisms underlying psychological factors in ASD is necessary to move develop our understanding. While the core deficits are common, there are clear differences in abilities with different levels of severity of autistic conditions. These differences affect adaptive behaviour as well as intervention opportunities and outcome in later life.
Teasing apart the complex causes of autism spectrum disorders will depend ultimately on the integration of information at all three levels of explanation &ndash genetics/neurobiology, cognition, and behaviour. This pursuit, though, must be addressed longitudinally if we are to appreciate fully the changes that take place throughout development.
Macedonian politicians should start to see this diagnosis as treatable and to invest the same power, money, and effort into treating ASD that they have put into treating other chronic medical disorders (cystic fibrosis, diabetes, cancer) that affect young children.

Conflict of Interest
The author declares no conflict of interest.

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How to cite this article: Trajkovski, V. Psychological aspects of autism spectrum disorder. Journal for ReAttach Therapy and Developmental Diversities, 2020 Jul 05 3(1):14-23. https://doi.org/10.26407/2020jrtdd.1.30

Copyright ©2020 Trajkovski, V. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0)


Is There A Strong Genetic Predisposition In Autism

For a while, the medical fraternity have been trying to answer a singular question: Is Autism Genetic? According to the latest research, scientists now believe that Autism is linked to a very strong genetic predisposition and is almost certainly hereditary in a majority of cases.

In a study that involved as many as 258 twins from a diversified ethnic and demographic background, the genetic influence on ASD (Autism Spectrum Disorder) was estimated to be anywhere between 74% to 98%.

Environmental and Genetic Make-up are the most commonly known causes of Autism

Some of the hereditary risk factors for Autism were also found to have a strong overlap with genes influencing less extreme or borderline autism symptoms that are available in the general population.

This recent study was conducted by the Institute of Psychiatry, Psychology & Neuroscience at King’s College, London. The paper has since been published in the JAMA Psychiatry journal.

Beata Tick, Lead Researcher, explains “The key finding out of our research was that the heritability of Autism Spectrum Disorder is much higher than we originally thought. By analyzing the results, we were also able to conclude that genetic factors may lead to a wide range of autistic symptoms and behavioral traits across the general population.

It is noteworthy that the results seem to indicate that genetic inheritance might well be among the key causes of Autism despite the dramatic increase in ASD prevalence over the last 20 years

The data source for this research was compiled from the TEDS (Twins Early Development Study) diversified population-based database. The research was funded by the Medical Research Council (MRC).

“A well-established approach, to clarify the extent of social, environmental and genetic influences in Autism, is to compare the commonalities between non-identical and identical twins”, says Professor Patrick Bolton, co-author and fellow member of King’s college.

Researchers believe that the ingenuity of this study lies in the fact that it included twins regardless of whether they had gone through a clinical diagnosis for Autism. This provided the theorists a holistic picture of the kind of influences that society, genetic makeup, and the environment has on the development of a child and how more subtle differences may manifest into pronounced autistic trends.

Their findings add more weight to the view that extreme manifestation of autistic traits and behaviors, observed in the general population, eventually leads to ASD.


Theories About Environmental Exposures

There has been a rise in cases of autism, and theories about why abound. While there are certainly people who believe there is a connection between some of the following and autism, there is no solid evidence to support this.

  • Ultrasound used to monitor fetal growth
  • Vaccines given to young children
  • Cell phone usage among parents
  • Allergies to peanuts and gluten
  • Prevalence of Lyme disease

Autism presents itself differently in different people. This suggests a variety of causes and, perhaps, a variety of syndromes with some (but not all) symptoms in common.


Modifiers in ASD

Genetic Modifiers

Though significant progress has been made in determining genetic causes of ASD, many aspects of how pathogenic variants regulate genetic susceptibility remain unknown. Individuals with the same variants can have widely heterogeneous disease presentations and levels of disability. Presence of second modulating variants that may interact with other susceptibility loci are one possible explanation of this heterogeneity. This “second hit” could be somatic – a phenomenon first proposed to cause disease by Alfred Knudson in the context of retinoblastomas – or in the germline, a “two-locus model” previously explored in conditions such as Hirschprung disease (Knudson, 1971 Fisher and Scambler, 1994 McCallion et al., 2003). To date, genetic evidence supporting a multiplex theory of autism has primarily been found for germline second-hits. Studies with CNVs will be discussed first, followed by a brief overview of known modulating SNPs. These investigations of how non-causative variants may modify the ASD phenotype are challenging to undertake, as few autistic individuals have the same pathogenic variants. In addition, there is not yet a complete understanding of which CNVs and SNPs are pathogenic in ASD.

One way to circumvent these issues is to investigate an autism subtype with a monogenic cause, such as Rett Syndrome. Artuso et al. (2011) used this strategy and identified 15 “likely” and 14 “unlikely” modulators of the RTT phenotype based on array comparative genome hybridization with eight RTT subjects. Another valuable approach is to assess monozygotic twins with a discordant phenotype. Several studies have assessed potential differences in CNVs or epigenetic regulation in discordant monozygotic twins, revealing potential methylation pattern differences in one case and anomalies in the 2p25.3 region in another (Bruder et al., 2008 Kunio et al., 2013 Rio et al., 2013). However, a study involving 100 twin pairs failed to find differences in CNVs that could explain the discordant phenotypes (Stamouli et al., 2018). The authors still acknowledge postzygotic mosaicism as a potential modifier and encourage more studies to help develop a clearer understanding of CNV modulating activity.

A handful of reports also exist of putative modifying CNVs in polygenic ASD cases with unrelated subjects. For example, Girirajan et al. (2012) found that children with two CNVs not known to be pathological were eight times more likely to be diagnosed with developmental delay than controls. In the same year, a study of SHANK2 pathogenic variants found abnormalities in both individuals with neuropsychiatric disease and controls, suggesting the presence of additional variants in order to cause disease. Three of the patients with de novo SHANK2 mutations were also found to have deletions of CHRNA7 and cytoplasmic FMR1 interacting protein 1 (CYFIP1) – both previously implicated in ASD – supporting a “multiple-hit” model of autism (Leblond et al., 2012). CHRNA7 was also suggested as a potential modifier in an earlier study by Szafranski et al. (2010). Barber et al. (2013) provided further support for a multiple-loci model of ASD upon finding that patients with 16p12.1 duplications had a more severe phenotype when a second large CNV was present. Included in these hypothesized modifier regions were genes G protein regulated inducer of neurite outgrowth 2 (GPRIN2) – previously implicated as a modifier in the study by Artuso et al. (2011) – and steroid sulfatase (STS), which was formerly thought to be non-causative (Li et al., 2010). More recently, an analysis of 20,226 patient records revealed 19 patients with CNVs in contactin 6 (CNTN6), a gene hypothesized to be involved in neurodevelopmental disorders including ASD (Repnikova et al., 2019). The authors were not able to find any significant genotype-phenotype relationships and concluded that CNV in CNTN6 were likely benign or modifying, but not causative of disease.

In addition to CNVs, there may be thousands of smaller pathogenic variants – such as SNPs and indels – that also modulate severity. For example, in a study of developmental delay, individuals that only carried a specific 16p12.1 microdeletion had a less severe phenotype than individuals with random second variants (Girirajan et al., 2010). One study of individuals with 22q11.2 deletion syndrome – all haploinsufficient for an mGluR network gene – found that 20% who were co-diagnosed with autism had second-hit pathogenic variants, while only 2% of 22q11DS individuals without autism had second hits (Wenger et al., 2016). Bonnet-Brilhault et al. (2016) assessed a family affected with ID and ASD due to NLGN4X pathogenic variants and found that individuals with ASD – but not ID or controls – had second-hit variants in glycine receptor beta (GRLB) and ankyrin 3 (ANK3). Additional evidence may exist, but GWAS and WES studies have tended to focus on causative susceptibility loci. Therefore, other variants which are not causative by themselves are not often emphasized or even reported. The emerging study of all types of genetic modifiers is a relatively recent development, and continuing advancements in sequencing technology, analyzing software, and expansion of databases should lay the framework for significant advancements in the near future.

Epigenetics and the Environment

Autism susceptibility is currently estimated to be 40�% genetic. Environmental factors – likely acting through epigenetic regulation as the major mechanism – presumably compromise the remainder of the risk. Hundreds of potential environmental factors have been suggested to contribute to risk, such as increased parental age (especially paternal), maternal complications or infections during pregnancy, or prenatal exposure to anticonvulsants (Rasalam et al., 2005 Kong et al., 2012 O’Roak et al., 2012 Ohkawara et al., 2015). In-depth reviews of these findings can be found elsewhere (Gardener et al., 2009 Chaste and Leboyer, 2012 Liu et al., 2016 Karimi et al., 2017 Modabbernia et al., 2017 Bölte et al., 2019). In this review, we will only discuss the epigenetic modifying effects of valproic acid – an anticonvulsant – as one example of the widespread modifications that an environmental factor can induce. Valproic acid has been hypothesized to modify gene expression through histone deacetylase inhibition activity and is sometimes used to induce an autistic phenotype in animal models (Kataoka et al., 2013). Examples of its far-reaching effects include apoptotic cell death in the neocortex, decreased proliferation in the ganglionic eminence, increased homeobox A1 (HOXA1) expression, abnormal serotonergic differentiation via Achaete-Scute family BHLH transcription factor 1 (ASCL1) silencing, disrupted serotonin homeostasis in the amygdala, dendritic spine loss, reduced prefrontal dopaminergic activity, and disruption of the glutamatergic/GABAergic balance (Stodgell et al., 2006 Dufour-Rainfray et al., 2010 Kataoka et al., 2013 Wang et al., 2013 Jacob et al., 2014 Takuma et al., 2014 Hara et al., 2015 Iijima et al., 2016 Mahmood et al., 2018).

In more thorough studies of the mechanism of action, Go et al. (2012) found that rats exposed to valproic acid in utero presented enhanced proliferation of neural progenitors and delayed neurogenesis by upregulating Wnt1 expression and activating the GSK-3β/β-catenin pathway, leading to macrocephaly. Another study found that valproic acid increased BDNF by two transcriptional mechanisms involving MeCP2 and tissue plasminogen activator (tPA). This increase in BDNF is proposed to alter neurite outgrowth, impairing synapse formation (Ko et al., 2018). Finally, Kolozsi et al. (2009) observed a downregulation of NLGN3 – a highly implicated autism risk gene involved in synapse formation – in both hippocampal and somatosensory cortex of valproate-exposed mice. Examples of other proposed environmentally modulated mechanisms of ASD risk exist, but the literature supporting valproic acid is an excellent example of the heterogeneous effects one environmental factor can induce. Further research is strongly needed to determine how the environment modulates ASD risk.

Clearly, epigenetics can have a profound impact on the transcriptome of an organism. Pathogenic variants in even one epigenetic-regulating gene or effects from the environment can cause widespread gene dysregulation. Epigenetic modulators can themselves be causative of disease, but they may also exacerbate or ameliorate the disease phenotype by influencing expression of risk genes. More genome-wide studies are needed to understand the common ASD epigenome, and whether certain epigenetic markings might be protective or detrimental to individuals who are genetically susceptible. In addition, more studies are needed to decipher epigenetics as a link between environmental risk factors and genetic susceptibility. There is a possibility that certain environmental factors could have protective epigenetic effects, providing potential avenues for therapy.

Sex-Linked Modifiers

It is well established that ASD affects males at much higher rates than females. The reasons for this are not yet completely clear. Some studies argue that differential expression between genders may result in an under-diagnosis of females, as males tend to present more external behavior (e.g., aggression or increased repetitive behavior) and females tend to present more internal behavior (e.g., depression and avoiding demands) (Werling and Geschwind, 2013). While this may contribute to the rates of diagnosis, other possibilities include that the female sex is protective and/or males are particularly vulnerable. This may be due to influence from hormones, genetics, or other unknown factors. The genetically heterogeneous nature of ASD makes it likely that all these elements are involved – sex bias varies drastically based on factors such as which CNVs are causative or which comorbidities are present, suggesting diverse means by which a sex bias may occur (Amiet et al., 2008 Polyak et al., 2015). Potential mechanisms of sex-specific modulation will be discussed briefly, although more thorough reviews are available elsewhere (Ferri et al., 2018).

Multiple studies argue that the female sex is protective toward ASD susceptibility (Robinson et al., 2013 Pinto et al., 2014). For example, the average mutational burden in diagnosed females is much higher than in males, suggesting that males have a lower mutational burden threshold (Jacquemont et al., 2014 Desachy et al., 2015). Another study by Robinson et al. (2013) investigated nearly 10,000 dizygotic autistic twin pairs and found that siblings of female probands had significantly worse symptoms than siblings of male probands. Many investigations have also found that unaffected mothers may carry the same mutation as their affected male children. One particularly well-documented example for this is the 15q11-13 duplication (Cook et al., 1997 Schroer et al., 1998 Gurrieri et al., 1999 Boyar et al., 2001). This region codes for GABAA receptors, which is supported by the observation of perturbed GABA signaling in ASD (Al-Otaish et al., 2018). The discovery that estrogens rescue ASD phenotypes in both zebrafish and mouse models of autism is an especially convincing piece of evidence for the female protective theory (Macrì et al., 2010 Hoffman et al., 2016).

It is also possible that the female sex is not protective, but males are particularly vulnerable. Three studies of gene expression patterns noted males generally had a higher expression of genes implicated in ASD, such as chromatin regulators and genes related to immune involvement (Ziats and Rennert, 2013 Shi et al., 2016 Werling et al., 2016). A study with rat models of ASD reported male-specific downregulation of MeCP2 leading to abnormal glutamate activity, providing another potential mechanism for male-specific vulnerability (Kim et al., 2016). Interestingly, multiple studies have found decreased levels of aromatase – an enzyme that catalyzes the conversion of testosterone to estradiol – in the brains of adolescent ASD individuals (Sarachana et al., 2011 Crider et al., 2014). Decreased aromatase has also been associated with decreased RAR-related orphan receptor A (RORA), an ASD-associated gene that is oppositely regulated by male and female hormones (Nguyen et al., 2010 Sarachana et al., 2011). Hu et al. (2015) found a much stronger correlation between RORA expression and that of its targets in the cortex of male mice relative to female mice, suggesting that RORA-deficient males may have greater dysregulation of genes than females.

Of course, there may also be a combination of female-specific protective and male-specific deleterious effects. For example, Jung et al. (2018) recently assessed sexually dimorphic traits in a CHD8 +/N2373K mouse model of autism. While male mice demonstrated abnormal social behaviors such as isolation-induced self-grooming, female behavior was similar to controls. Neuronal excitability was also enhanced in males and suppressed in females. Transcriptomes were distinct, with female mice revealing an enrichment for ECM molecules, likely providing a protective effect.

A likely mechanism of divergent modulation is from differential effects of sex hormones, which have been hypothesized to play an important role in ASD pathology for both males and females (Baron-Cohen et al., 2005, 2015 Whitehouse et al., 2010 Honk et al., 2011 Ferri et al., 2018). For example, testosterone and estrogen have been shown to have contrasting effects on the immune system (Lenz et al., 2013 Roved et al., 2017), which has been repeatedly shown to play a pathological role in ASD (Estes and McAllister, 2015 Koyama and Ikegaya, 2015 Kim et al., 2017 McCarthy and Wright, 2017 Nadeem et al., 2019). Schwarz et al. (2011) analyzed biomarkers from individuals with Asperger’s syndrome and found 24 male-specific and 17 female-specific hits, including many immune-related molecules. Spine density, another phenotype strongly implicated in autism (Comery et al., 1997 Irwin et al., 2001 Hutsler and Zhang, 2010 Durand et al., 2012 Takuma et al., 2014 Tang et al., 2014 Liu et al., 2017a, b Soltani et al., 2017), is also affected by testosterone (Hatanaka et al., 2015). Key molecules involved in neurotransmission such as GABA, glutamate, serotonin, and BDNF are all implicated in ASD and modulated by sex hormones (Kim et al., 2016, p. 2 Saghazadeh and Rezaei, 2017 Al-Otaish et al., 2018 Edwards et al., 2018 Ferri et al., 2018 Garbarino et al., 2018 Zieminska et al., 2018). It is not yet clear whether the majority of differences between male and female presentation of ASD arise from differential regulatory actions of sex hormones or from other modifiers, but the presence of a sexually dimorphic phenotype is well established. Future research will likely elucidate a clearer picture of the identity and mechanisms of sex-specific modifiers.


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Autism results from an interplay between genetics and the environment. Dozens of genes have been implicated in the condition, but on the environmental side of the equation, it has been tough to nail down the factors involved.

Here, we explain why it is difficult to link autism to environmental factors, and what scientists know about how the environment influences autism risk.

What qualifies as an environmental risk factor?
The term ‘environmental risk factor’ is usually understood to mean the chemicals or pollutants a person is exposed to. But scientists use a broader definition: An environmental risk factor is anything that alters the likelihood of having a condition and isn’t encoded in an individual’s DNA.

Environmental risk factors for autism include being born prematurely, soon after an older sibling or to a mother with diabetes, for example. Over the past 15 years or so, scientists have investigated many of these factors to determine how they may contribute to autism. But there’s still little definitive information.

Why don’t we know which environmental factors increase risk for autism?
Studies of the environment’s link to autism have returned inconsistent results. For example, some studies suggest that taking antidepressants during pregnancy increases autism risk in the child others find no such link.

Most research on environmental risk comprises epidemiological studies, which identify associations between something in the environment and the likelihood of a diagnosis in large groups of people. But those studies do not demonstrate cause and effect.

For one thing, they are rife with what scientists call ‘confounding factors’ — variables that tend to travel together and make it difficult to pinpoint causal relationships.

What’s more, the causal relationships can be unclear. For example, we know that children with older fathers are more likely to have autism than those who have younger fathers. But we don’t know whether advanced paternal age itself increases autism risk or whether men who carry more genetic risk factors for autism, and perhaps display traits of the condition, tend to have children later in life.

Environmental factors are also often difficult to measure. Parents may be unaware of, or forget, what they and their child were exposed to. Or they may attach outsized importance to any detail they think could explain their child’s autism.

Which environmental risk factors for autism are well established?
The most widely accepted risk factors operate during gestation or around the time of birth. Various pregnancy and birth complications are associated with an increased risk of autism. These include preterm birth, low birth weight and maternal diabetes or high blood pressure during pregnancy. Scientists are not sure of the mechanisms underlying these associations.

The maternal immune system appears to play a role in autism risk. Infections, serious illnesses, such as a bad case of influenza, and hospitalizations during pregnancy are all linked to an increased risk of autism in a child. Women with autoimmune diseases, in which the body attacks its own tissues, are also at an elevated risk of having an autistic child. And animal studies suggest that certain immune molecules can alter gene expression and brain development in ways that may be relevant to autism.

Exposure to the drug valproate, which is used to treat bipolar disorder and epilepsy, in the womb is known to increase the risk of autism, as well as a variety of birth defects.

What other factors are scientists investigating?
Scientists are still trying to tease apart the effects of maternal antidepressant use during pregnancy from those of depression itself. One reason this issue has been difficult to settle is that if a parent has a brain condition, his or her child may carry shared genetic factors that increase autism risk.

Evidence that exposure to air pollution during gestation or early life increases a child’s risk of autism has grown more robust over the past few years. Still, many questions remain, such as which of the many components of air pollution might be involved.

Which proposed risk factors have been ruled out?
Despite the links between maternal immune factors and autism, routine vaccinations given during pregnancy, such as those against influenza and whooping cough, do not appear to boost autism risk.

Childhood vaccines are similarly in the clear. The research that purported to show a causal link was fraudulent and has been retracted, and no reliable evidence has ever emerged to support it.

Scientists have also exonerated smoking during pregnancy as a contributor to autism. Of course, smoking during pregnancy is harmful for many other reasons.

Are there any environmental factors that lower the risk of autism?
Scientists are trying to identify environmental risk factors for autism so that they can find a way to lower the risk. But the factors backed by the strongest evidence are not easy to modify.

Some studies suggest that taking vitamin D and vitamin B-9, or folic acid, supplements during pregnancy can decrease the baby’s autism risk. But the evidence is not definitive.

What are scientists doing to find out more?
New statistical techniques are helping scientists tackle confounding factors and draw more robust conclusions from epidemiological studies. Animal studies provide evidence about the mechanisms by which particular factors increase or decrease autism risk. And several efforts, such as the Environmental influences on Child Health Outcomes study and the Early Markers for Autism study, are tracking environmental exposures and risk factors in children, starting before birth.

What should parents and prospective parents do?
Families who are at high risk of having a child with autism — because they already have one child with the condition, for example — should consult with their doctor or a genetic counselor for specific recommendations. For most people, though, the general recommendations given to pregnant women (get a flu shot, take prenatal vitamins) are unlikely to cause harm and may even help.

It’s also important to remember that even for environmental factors that do appear to increase autism risk, the absolute risk of having a child with autism is small. For example, a large 2014 study of women in Sweden revealed that having an infection during pregnancy increases the risk of having a child with autism from 1 percent to 1.3 percent.


Theories About Environmental Exposures

There has been a rise in cases of autism, and theories about why abound. While there are certainly people who believe there is a connection between some of the following and autism, there is no solid evidence to support this.

  • Ultrasound used to monitor fetal growth
  • Vaccines given to young children
  • Cell phone usage among parents
  • Allergies to peanuts and gluten
  • Prevalence of Lyme disease

Autism presents itself differently in different people. This suggests a variety of causes and, perhaps, a variety of syndromes with some (but not all) symptoms in common.


What Causes Autism Spectrum Disorder?

Genetic factors play a big role in causing autism spectrum disorder, but researchers suspect environment is also involved.

Autism spectrum disorder (ASD) is a neurodevelopmental condition — a group of conditions involving brain differences that can affect behavior, memory, communication, and learning.

Autism is complex, and no two autistic people are the same. Because of this, researchers believe there are probably many causes of autism, including genetic and environmental factors.

So far, some evidence suggests that changes (aka mutations) in a person’s genes could cause autism. Other research suggests that a combination of genes and environment may contribute to the causes.

Many autistic people view autism as part of their identity — not as a condition to be treated or prevented. So, some people are now saying that research on its causes isn’t the best use of resources, since some of this is centered around prevention.

Some autistic people and advocates suggest research and resources that support autistic people are much more helpful.

Many experts believe genes play the biggest role in causing autism. A 2019 study estimated that about 80% of autistic people have it due to genetics.

Research has found more than 800 genes linked to autism. Recently, researchers reported that more than 100 genes are implicated in developing autism.

While research suggests that many autistic people have small mutations in a lot of their genes, it’s not always clear how big of a role these mutations play.

In fact, many autistic people have different mutations, and some don’t show the genetic changes that are often connected to autism. This means that different mutations probably play different roles in causing autism.

For example, some mutations or combinations of mutations could:

  • play a role in causing certain behaviors
  • contribute to whether someone needs minimal or significant support
  • increase a person’s chances of having autism

Other genetic factors that could increase someone’s chances of developing autism include:

  • assigned male at birth
  • having an autistic sibling
  • a chromosomal condition like fragile X syndrome

Because we tend to have more control over environmental factors, researchers have put effort into studying environmental causes of autism.

So far, research suggests that the most influential factors that increase a person’s chances of developing autism are related to what happens before and during birth, like if:

  • the fetus is exposed to air pollution or certain pesticides before birth
  • the pregnant parent has diabetes or another immune system disorder
  • the baby is born before 36 weeks old
  • there were birth complications like the baby was breech, in fetal distress, or had a low birth weight
  • there were any issues during birth that caused a limited amount of oxygen to the baby’s brain

These factors likely don’t cause autism by themselves. For instance, many babies are born before 36 weeks, with and without autism.

Researchers have also looked into other biological factors connected to autism. These factors are involved with:

Some research links certain immune system issues with autism.

The same research suggests that some infections during pregnancy could increase the child’s likelihood of having autism. Several other immune issues may also increase likelihood, including:

  • problems with how the immune system works
  • inflammation
  • developing antibodies to a condition they haven’t been exposed to

Another possible factor linked to autism? How well an autistic person’s mitochondria (the “powerhouse” of the cell) work. Mitochondria create the majority of a cell’s energy and are an important part of metabolism, among other things.

Recent research has found that there may be a link between mitochondrial function and autism.

Additionally, scientists suggest that mitochondria are also affected by some of the same environmental factors that can increase the chances of someone being diagnosed with autism.

Other factors that may play a role in someone’s chances of developing ASD include:

  • the frontal cortex of the baby’s brain overgrows shortly after birth
  • the baby is male (autism is 4 times more common in boys than girls)
  • advanced paternal age

An autism diagnosis may also be more likely if during pregnancy, the parent:

  • had hypertension or diabetes
  • experienced an antepartum hemorrhage in the third trimester or postpartum hemorrhage
  • has given birth to more than 4 children
  • had preeclampsia

Some people believe that vaccines cause autism. This isn’t true.

According to many organizations, including the Centers for Disease Control and Prevention (CDC) , there’s no evidence that vaccines cause autism.

This belief comes from a study published in the British medical journal, Lancet, in 1998. The study concluded that the measles, mumps, and rubella (MMR) vaccine caused autism.

The study wasn’t properly conducted, and it was later retracted and disproven. But it gained a lot of publicity, and some people still believe the false findings are true.

Other factors, like smoking during pregnancy, exposure to mercury, or fertility treatments are also believed to cause autism. None of these causes have been proven.

Autism is diagnosed by a medical professional, often a pediatrician or specialist.

According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), an autistic person must have both social and behavioral patterns that meet the criteria for autism spectrum disorder.

Someone might receive an autism diagnosis at 18 months or younger, but it’s more common to get diagnosed around 2 years old.

Still, some people don’t get a diagnosis until much older or until adulthood.

When diagnosing ASD, clinicians may look for patterns in communication like:

  • difficulty with back-and-forth conversation
  • differences in nonverbal communication like facial expressions or body language
  • difficulty adjusting behavior to different social settings

A doctor may also look at these behavioral patterns when screening for autism:

  • specific movements, actions, or gestures
  • strong attachment to routine
  • specific, strong interests
  • differences in sensory processing

Many autistic people see autism as an identity, not as a condition to be treated. But if you’re experiencing challenges related to being autistic, there are many ways to find support, depending on your needs.

If you’re a parent of an autistic child, you can get some tips for how to support your child here. And if you’re an autistic adult, you can learn more about strategies, support, and therapies here.

When learning what kinds of resources your autistic child needs, it can help to research your options and talk to doctors. Deciding what’s best for your child will depend on the level of support they need and what’s available to you.

While there’s no single way to support autistic people, professionals often agree that the earlier you can connect with support services, the better. Many forms of support — especially for autistic children — can help them feel safe and understood.

Autism is complex. While genetics may be a key factor in causing autism, it’s likely that a person’s environment and other factors also play a role.

Researchers have found more than 800 genes linked to autism. While we still don’t know as much about environmental or biological factors, researchers have made progress.

No matter what causes autism, there’s plenty of opportunities for autistic people to live well and find the support that works for them.


Genes and ASD

Genes: Bits of DNA that carry instructions for "building" your body.

Chromosomes: Packages of DNA and genes in the cells of the body.

A great deal of evidence supports the idea that genes are one of the main causes of or a major contributor to ASD. More than 100 genes on different chromosomes may be involved in causing ASD, to different degrees. 3,4

Many people with autism have slight changes, called mutations, in many of these genes. However, the link between genetic mutations and autism is complex:

  • Most people with autism have different mutations and combinations of mutations. Not everyone with autism has changes in every gene that scientists have linked to ASD.
  • Many people without autism or autism symptoms also have some of these genetic mutations that scientists have linked to autism.

This evidence means that different genetic mutations probably play different roles in ASD. For example, certain mutations or combinations of mutations might:


Is autism caused by genetics? - Psychology

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July 5th, 2020

Neuropsychological Research

PSYCHOLOGICAL ASPECTS OF AUTISM SPECTRUM DISORDER

1. Introduction

Autism spectrum disorder (ASD) is a pervasive developmental disorder that has both fascinated and frustrated scientific and clinical researchers. It is a major mental health, educational and social medical challenge. Autism has epidemic proportions worldwide. The Centre for Disease Control and Prevention states that autism spectrum disorder occurs in about 1 in 54 eight year old children in the USA (Maenner et al., 2016). Unfortunately, in Macedonia, there is no statistical data about the prevalence of this condition. The etiology and neuropsychological basis of this complex disorder still remains uknown. The perspective of a psychological model of autism is that the social and communicative impairments reflect fundamental difficulties in understanding other people as mental beings &ndash the so-called &ldquotheory of mind&rdquo hypothesis of autism (Tager-Flusberg, 1999). It is a life-long disorder that has a substantial effect on the individuals, their family, and society as well. Autism is a complex neurodevelopmental disorder encompassing severe abnormalities in reciprocal social interaction, verbal and nonverbal communication, accompanied by restricted and repetitive behaviours and interests. These behavioural symptoms are present in very early childhood, before the age of 3 years. There is much variability in the disorder in terms of intellectual functioning, language ability, and severity of behavioural symptoms, (APA, 2013). This creates psychological and social impacts on affected individual and creates problems for parents in dealing with the children with ASD. This disorder is a major economic burden for all societies in the world.
It is a spectral disorder where some individuals with ASD are mildly affected by their symptoms some are moderate impaired, whereas the others are profoundly affected. There is major heterogeneity in ASD, and the range of ASD symptoms can be classified into broad categories of core symptoms and secondary symptoms. Secondary symptoms can include conditions such as intellectual impairment, which occurs in approximately 70% of patients with ASD, aggressiveness toward others, self-injury, eating disturbances, sleeping disorders, and seizures. Clinical characteristics are changeable throughout the lifespan. For example, language difficulties and hyperactivity that is often seen in younger children can shift to relational problems, mood dysregulation, and hypo-activity in adolescence and young adulthood. Diagnosis of ASD can be challenging, but progress has been made in refining diagnostic processes that can be addressed over the lifespan (Elder et al., 2017).
Children with ASD are more exposed to social stigmatisation and social rejection due to a lot of prejudice. Apart from stigma, Macedonia has a lack of treatment facilities, lack of trained child special educators and psychologists, lack of diagnostic procedures, lack of awareness among people, poor attention and poor resources from the government and a lack of proper welfare facilities, education facilities and rehabilitation services for children with ASD. Social institutions at the local level are not capable of ensuring that people with autism can remain in their area of residence and be provided with adequate educational and social services. The lack of statistical data on people with a disability hampers an evaluation of whether all people with any given disability are socially jeopardised and if they are able to access their rights in the field of social care. The Law on social protection established measures and services in the field of social protection and social care through social prevention, de-institutional care, protection and the right for social support (Trajkovski, 2008).
People identified with autism spectrum disorders have high frequencies of one or more co-occurring non-ASD developmental, neurologic, psychiatric, metabolic, immune, gastrointestinal and possibly causative medical diagnoses. Seizures, disturbed sleep and painful gastrointestinal disorders are some of the health conditions commonly associated with autism. Autism is frequently accompanied by mental health conditions including anxiety, depression, and ADHD. Medical conditions and consecutive pathological processes can negatively impact behavior, socialization, communication, cognitive function and sensory processing of individuals with autism. Accurate diagnosis and treatment often results in improved level of functioning and decreased severity of symptoms (Trajkovski, 2018).
Psychologists complete assessments of children with autism. The assessment can be related to diagnosis, cognition (IQ) or the way a child with autism thinks and sees the world. Psychologists have focused their efforts on the cognitive level of explanation in order to identify the underlying processes that might account for the various behavioural manifestations of the disorder. Historically, and in the interests of parsimony, the emphasis upon these theories has been to posit a single primary cognitive deficit that could explain the development of autism. Theories from three cognitive domains have dominated the field: theory of mind &ndash the ability to reason about the mental states of others executive control &ndash a set of abilities important for flexible behaviour in novel circumstances and central coherence &ndash the natural propensity to process information in context (Pellicano, 2007).
The purpose of this review article is to create an overview of current knowledge on the most prominent psychological factors that format and are formatted by the development of ASD. Also, the other goal is to explore diagnostics and treatment from a psychological perspective.

2. Psychologic functions in ASD

In the following pages, psychologic functions, which are altered in ASD, will be described such as attention, executive function, academic functioning, memory, emotions, and sensory processing.

2.1. Attention

Attention is a concept studied in cognitive psychology that refers to how we actively process specific information in our environment. Attention is a multi-dimensional construct that encompasses several components, including focusing, sustaining, and shifting operations, (Mirsky et al., 1999). Children with ASD do not usually have problems with sustained attention. They have problems with focusing attention, although their pattern is different from that of children with attention-deficit/hyperactivity disorder (ADHD). Those with ASD tend to &ldquomiss the forest for the trees&rdquo or over-focus attention on extraneous details while missing meaning. This difficulty has also been called impaired central coherence, (Happe and Frith, 1996). Children with ASD are more distracted by internal phenomena (e.g., special interests) than those with ADHD, whose attention is more typically diverted by external stimuli in the environment. Some children with ASD do exhibit classic ADHD symptoms of distractibility and hyperactivity (Ghaziuddin et al., 1992). Attentional abnormalities have long been documented in individuals with ASD using a variety of experimental paradigms and tasks. The predominant model of attention puts forward three critical components: alerting, orienting, and executive (Petersen and Posner, 2012). The alerting component of attention includes the ability to produce and maintain optimal vigilance and performance during tasks. The orienting component of attention includes the ability to prioritise sensory input by disengaging, shifting, and re-engaging attention to a modality or location. The executive component of attention includes resolving conflict among competing responses. Sensory issues and attentional issues are closely connected to each other.

2.2. Executive function

Executive function describes a set of cognitive processes and mental skills that help an individual to plan, monitor, and successfully execute their goals. These include attentional control, working memory, inhibition, and problem solving many of which are thought to originate in the brain&rsquos pre-frontal cortex. One of the most consistently replicated cognitive deficits in individuals with ASD, is executive dysfunction, (Ozonoff and Jensen, 1999). The executive function domain includes the many skills required to prepare for and execute complex behaviour, including planning, inhibition, organisation, self-monitoring, mental representation of tasks and goals, and cognitive flexibility and set shifting.
Executive attention has also been shown to be impaired in young people with ASD. School-aged children and adults with ASD demonstrate larger flanker effects, i.e., slower response when the flanking arrows are pointing in an incongruent direction from the central target arrow (Mutreja et al., 2015), though there are some negative findings as well (Geurts et al., 2008). Executive function is defined as the ability to regulate one&rsquos thoughts, emotions, and actions in order to achieve volitional goals (Zelazo et al., 2008). Executive function is one of the most studied cognitive constructs in ASD with more than 400 empirical articles since 1985 that have been covered across several comprehensive reviews (Wallace et al., 2016) and meta-analyses (Lai et al., 2016). This heavy investigation has been driven by long-standing clinical observations that individuals with ASD show executive function impairments. While intensive investigations have demonstrated that early executive function impairments are not causal of ASD, executive function skills can predict some forms of mentalising, repetitive behaviours, adaptive function skills, academic readiness, and challenging behaviours. In the following sections, we will review research in the three core components of executive functioning: updating, shifting, and inhibition, (Miyake and Friedman, 2012). Examination of more complex executive function tasks, like Tower tasks that tap into planning and organisation skills or Verbal Fluency tasks that tap into generativity skills, reveal impairments of a moderate effect and size in individuals with ASD compared to controls. Furthermore, performance in tasks assessing planning, appear to be significantly influenced by co-occurring ADHD symptoms, while this is not the case for tasks assessing generativity skills (Lai et al., 2016).

2.3. Academic functioning

It is very important to assess academic skills, even in younger children, for the purposes of educational decision making. Many children with ASD have precocious reading skills and can decode words at a higher level than others of the same age and functional ability. The first set of difficulties relates to the ability of students with autism to attend in traditional educational environments. These students have difficulty completing an activity from start to finish. Reading and other academic strengths can be used to compensate for weaknesses, as when a written schedule is provided to facilitate transitions or written directions are supplied to improve compliance. The good memory of children with ASD may mean that spelling lists and multiplication tables are learned more easily. Specific areas of weakness also exist, with the most consistently demonstrated one being reading comprehension. Whether communicating information about routines, academic content, or social expectations, teachers use verbal language. For many learners with autism, this strategy is ineffective. They are unable to process complex verbal information. They cannot understand abstract notions.
It is important that appropriate test batteries that assess both academic strengths and weaknesses be included in a comprehensive evaluation of a child and the learning patterns they suggest be interpreted in the feedback to parents and appropriate educational recommendations are made in the written report.
The performance profile seen in measures of academic function is consistent with that obtained from intellectual tests. Academic skills requiring primarily rote, mechanical, or procedural abilities are generally intact, while those relying upon more abstract, conceptual, or interpretive abilities are typically deficient. Some authors in the reading domain found that individuals with high-functioning autism performed as well as or better than normal controls matched on age and IQ on tests of single-word oral reading, non-word reading, and spelling (Minshew et al., 1994). These measures all require phonological decoding skills and thus indicate preserved or even advanced knowledge of grapheme&ndashphoneme correspondence rules in autism. In contrast, subjects with autism performed less well than controls on two measures of reading comprehension. This pattern, in its most extreme form, is named hyperlexia. It is used to describe individuals with word recognition skills that are significantly better than predicted by intellectual or educational level. Hyperlexia has been documented in individuals with autism by a number of researchers (Nation et al., 2006). The cognitive and social communication characteristics serve as the basis for the development of systematic instruction and the use of visually structured environments. Students with autism may have difficulty learning in distracting environments.

Memory refers to the processes that are used to acquire, store, retain, and later retrieve information. There are three major processes involved in memory: encoding, storage, and retrieval. Memory has been a focus for researchers in search of basic psychological factors that contribute to the development of ASD (Boucher et al., 2012). Non-declarative memory includes perceptual memory (automatic and unconscious memory) and procedural memory (conditioning, habit memory, the learning of sensorimotor or cognitive skills). Declarative memory is the explicit acquisition and maintenance of information over a longer time.
Non-declarative memory appears to be largely intact in individuals with ASD without ID, particularly when stimuli are non-social in nature. Tasks include implicit learning tasks, in which children are repeatedly exposed to a stimulus and learning is reflected in faster (and/or more accurate) responses over trials. Intact performance is observed in implicit motor sequence learning (Travers et al., 2010) and spatial context learning (Kourkoulou et al., 2011). However, there is some preliminary evidence of a slower adaptation of learning when the learning task biases individuals with ASD toward local features of a stimulus. Other non-declarative tasks that reveal intact performance in ASD include perceptual or conceptual priming for words, pictures, and music. However, fear conditioning tasks, in which participants are repeatedly exposed to a stimulus and learning is reflected in faster (and/or more accurate) response over trials, have revealed impairments in adults with ASD (Gaigg and Bowler, 2007).
Declarative memory research in ASD is characterised by a pattern of mixed findings of intact and impaired performance across tasks, moderated by cognitive ability. Recognition memory tasks involve the presentation of a list of stimuli (e.g. words, aurally or visually). Subsequently, participants are tested by being shown a group of stimuli (e.g. list of words) that were either part of the to-be-remembered group (targets) or not (foils). Performance has been reported as largely intact in individuals with ASD without ID for tests using nonsocial stimuli, such as lists of words, stories, and pictures of common objects. However, recognition memory may be impaired in verbal individuals with ASD and ID, and when face stimuli are used. Free recall tasks which require individuals to remember unrelated words revealed no impairments in individuals with ASD across age and immediate or delayed recall conditions however, control groups outperformed individuals with ASD when semantically related word lists were used, suggesting that non-ASD populations were able to make use of this higher-order category to support memory (Bowler et al., 2008).

2.5. Motor development

Motor development refers to the development of a child&rsquos bones, muscles and ability to move around and manipulate things in an environment. Motor development can be divided into two sections: gross motor development and fine motor development. Children with autism tend to also have motor difficulties. Early descriptions of these children suggest that they were graceful and skillful and had few signs of motor impairment. This was part of the puzzle relating to the origins of the disorder. Later systematic studies of motor performance in low-functioning cases uncovered clear signs of delayed or abnormal motor and sensorimotor development (Jones and Prior, 1985). One author found motor imitation problems in children with high-functioning autism and basic motor functioning problems or dyspraxia which were significant handicaps to imitation (Bennetto, 1999). Problems in producing gesture, either by imitation or spontaneously, may underlie the well-known failure of children with autism to use gesture to communicate like neuro-typical children. Motor dyspraxic and neurodevelopmental signs such as choreiform movements, gait abnormalities, balance problems, and impaired body imitation abilities are significant characteristics of autism (Goldstein et al., 2001).
Motor problems are showed to be slow in a substantial proportion of cases (DeMyer et al., 1981), although it is unknown whether neurologically impaired children with autism are different in other significant ways from those without measurable signs on these indices. Some authors compared children with autism with those who had language disorders and with controls on a neurological examination. They found motor problems across balance, coordination, fine, gross and oromotor functions (Noterdaeme et al., 2002). Using standardised tests of motor impairment and including children with Asperger&rsquos syndrome and higher-functioning autism as subjects (Ghaziuddin et al., 1994), it has been shown that both groups show signs of neuro-motor clumsiness across a range of motor systems. Their graphomotor scores, as ascertained from testing with standard visuomotor tests, remained an area of weakness in ability profiles from early to later ages. In the academic domain, although the higher IQ group had normal range scores in numeracy and literacy, their written expression was a notable weakness. Ongoing problems with written work in the school curriculum, which of course requires fine motor skills and effort (Manjiviona, 2003).
Research examining deficits in motor execution and motor planning was also presented and opens up avenues for further research. The use of magnetic resonance imaging, to establish abnormalities in neural underpinnings of motor control, is one possibility. Motor dysfunction of individuals with autism, poses concerns for parents and professionals. Delayed motor development will impact on physical activity participation and the development of daily living skills for individuals on the autistic spectrum. This clearly indicates the need for intervention studies to examine the effects of physical activity on the motor development of individuals with ASD.

2.6. Emotional processing

Emotional processing happens when an individual experiences an emotionally distressing event and is able to cope with those experiences over time to the extent that new experiences can occur (whether stressful or not) without a return to the previous distress. While individuals with ASD feel and express emotions, their emotional expressions are reduced in frequency and manifested in more ambiguous ways compared to those of typically developing individuals, as reflected across facial expressions, body postures, spontaneous language and prosody (Brewer et al., 2016). Individuals with ASD have difficulties recognising emotions in others from their facial and bodily expressions, and their prosody. Emotion processing difficulties appear to vary greatly across individuals and studies (Nuske et al., 2013), with more pronounced difficulties reported in tasks testing recognition of complex versus simple, intense versus subtle, and negative versus positive emotions.
Empathy is another area of weakness in ASD, although recent studies suggested that difficulties in this area are related to the cognitive dimension (understand what others are feeling) rather than the affective dimension (feeling concern in response to others&rsquo emotions) of empathy (Mazza et al., 2014). Recent work by (Schwenck et al., 2012) has pointed to a double dissociation, where individuals with ASD were selectively impaired in cognitive empathy, while those with conduct disorder were selectively impaired in affective empathy. Atypicalities in the emotion processing domain are more frequently reported in studies testing brain and physiological responses to emotional displays, compared to behavioural studies. Findings include atypical physiological arousal and reduced brain activity in emotion processing circuitries in response to emotional scenes, and emotional prosody. Emotion processing difficulties have been reported to increase with age, and to be associated with lower social skills as well as lower verbal and non-verbal cognitive functioning. It is still debated whether such abnormalities in ASD represent a primary deficit in emotion processing, a manifestation of social impairments (possibly involving social-motivational and social-cognitive factors), or the final outcome of multiple social and non-social abnormalities (Vivanti et al., 2019).

2.7. Problems with sensory processing

Sensory processing refers to the way the nervous system receives messages from the senses and turns them into responses. Through the senses, we learn about our environment as well as ourselves, creating memories that contain records of our history of sensory experiences. The presence of sensory disorders in children with autism is widely recognised nowadays. The range of such sensory dysfunctions is considerable and includes tactile, auditory, visual, olfactory and gustatory hyper or hypo sensitivity. Tactile hypersensitivity is evidenced by the aversion to wearing certain types of clothing, walking on grass or textured flooring or handling certain types of objects and materials. Some individuals show extreme anxiety in social situations because of their tactile hypersensitivity. A person with visual processing differences may have difficulties with bright or flashing lights, such as fluorescent lights. A restricted diet and refusal to eat particular foods is also common in children with autism. It is not always clear whether the refusal is related to the taste, smell or texture of the food or some combination of these characteristics.
In addition to hypersensitivity, some individuals show reduced sensitivity (hypоsensitivity) to pain, cold and sound, as well as a wide range of other sensory inputs. In contrast, other people with autism appear to be strongly attracted to certain types of stimuli to the extent that they can fixate on them and tend to maintain that stimulation through repetitive and compulsive behaviours. For example, some children crave deep pressure stimulation. There are individuals who are particularly attracted to scents and tend to smell everything. There are speculations that some children’s reading difficulties may be related to letters that appear wavy or completely missing. Some sensory problems may reflect the inability to coordinate or integrate sensor input from multiple sources or multiple sensing modalities. Children with this last type of problem may find it difficult to follow a conversation when there are background sounds or have visual stimulus problems when speaking. It is also speculated that sensory interference (synesthesia) may occur in some individuals if the person can see sounds or hear pictures. Finally, some sensory dysfunctions include the vestibular system that helps regulate balance and movement, and the proorption system that provides feedback from muscles, tendons, and ligaments on body posture (Huebner, 2001).

3. Diagnosis of ASD from a psychological perspective

The process of establishing an ASD diagnosis and linking to early intervention and support services is often a major challenge. The processes include: identifying diagnostic needs for ASD, ensuring accurate assessment by a trained professional, and opening up appropriate ASD child services that include complex individual, social and medical factors that are often difficult to manage from a logistical and financial perspective (Lappé et al., 2018). The list of experts which can make the diagnosis is long and it includes: paediatricians, neurologists, and psychologists. The expert making the diagnosis should have extensive experience working with the wide range of symptoms. To make a diagnosis of ASD, psychologists draw on a number of sources of information: patient interviews, observations of the patient&rsquos behaviour, tests of cognitive and language abilities, medical tests to rule out other conditions, interviews with parents, teachers or other adults who can answer questions about the patient&rsquos social, emotional and behavioural development. Psychologists, working in partnership with physicians, speech and language pathologists, and occupational therapists, can lead or contribute to multi-disciplinary diagnostic teams in clinical settings. Psychologists are skilled in diagnostic practices and the assessment of cognitive and behavioural functions. After the evaluation is complete, they often play important roles in treatment and case management, making referrals to community resources, setting up interventions in schools and homes, and providing various therapies for both children and families.

4. Treatment of ASD from a psychological perspective

Children with ASD benefit from interdisciplinary treatment teams made up of various experts from various fields. Those teams typically include physicians, special educators, speech therapists, occupational therapists, and psychologists. Several interventions have been developed to treat children with ASD. Some of the most common evidence based approaches include following: Applied Behaviour Analysis (ABA), Developmental Individual-Difference Relationship-Based model (DIR), and TEACCH. ABA is an intensive method that uses teaching techniques to increase helpful behaviours and reduce behaviours that are harmful or interfere with learning. ABA therapy has been shown to improve communication, social and vocational skills. In the DIR model, also known as floor-time therapy, parents and therapists follow the child&rsquos lead in playing together while also directing the child to engage in increasingly complex interactions. The TEACCH framework promotes engagement in activities, flexibility, independence and self-efficacy through strategies based on the learning strengths and difficulties of people with ASD. There are some other promising treatments such as: Reattach therapy, Sensory Integration Therapy and art and drama therapy. These interdisciplinary treatments can improve a variety of abilities required for daily life, for example, dressing, eating, and fine motor developments, which can assist somebody with ASD and manage their sensory overload (e.g.: sights, sounds, touch, etc.). The child should be evaluated by a professional trained in diagnosing and treating autism, so that he or she can recommend the most appropriate interventions. Such interventions can be administered by psychologists, as well as by special educators and board certified behaviour analysts. Psychologists also play an important role in helping children of all ages as well as adults with ASD manage specific challenges associated with the disorder (APA, 2019).

5. Conclusion

Autism spectrum disorder is probably the most misunderstood and puzzling of the neurodevelopmental conditions. This article focusses on the psychological aspects of ASD and diagnostics and treatment from a psychological perspective. While major advances have been made in the field, it is clear that more special education services are needed, together with timely and ongoing psychosocial support to parents of children with ASD. It is clear that ASD is a lifelong condition and families must learn to shift their focus from treatments to developing life-skills as their child grows into adulthood. They should not need to rely on possible misinformation on the internet. Effective communication between service providers and families is the key to building supportive relationships that can positively affect not only the individual with ASD but also the family over a lifetime.
Individuals with ASD possess strengths of character, unique skills, and untapped resources that should not be undervalued or unappreciated. The professional discussion of these qualities communicates a belief that individuals with ASD and their families can do more than simply survive. They can live enriched and fulfilling lives and they can be valued for what they can offer to society. Some individuals with ASD, particularly those with better language and intellectual skills, can live and work independently as adults. They should have support to access employment in their community. The degree of malleability of core and associated ASD features remains unclear, as treatment effects attained in research settings are not always replicated in community settings, and more research on the mechanisms underlying psychological factors in ASD is necessary to move develop our understanding. While the core deficits are common, there are clear differences in abilities with different levels of severity of autistic conditions. These differences affect adaptive behaviour as well as intervention opportunities and outcome in later life.
Teasing apart the complex causes of autism spectrum disorders will depend ultimately on the integration of information at all three levels of explanation &ndash genetics/neurobiology, cognition, and behaviour. This pursuit, though, must be addressed longitudinally if we are to appreciate fully the changes that take place throughout development.
Macedonian politicians should start to see this diagnosis as treatable and to invest the same power, money, and effort into treating ASD that they have put into treating other chronic medical disorders (cystic fibrosis, diabetes, cancer) that affect young children.

Conflict of Interest
The author declares no conflict of interest.

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How to cite this article: Trajkovski, V. Psychological aspects of autism spectrum disorder. Journal for ReAttach Therapy and Developmental Diversities, 2020 Jul 05 3(1):14-23. https://doi.org/10.26407/2020jrtdd.1.30

Copyright ©2020 Trajkovski, V. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0)


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Autism results from an interplay between genetics and the environment. Dozens of genes have been implicated in the condition, but on the environmental side of the equation, it has been tough to nail down the factors involved.

Here, we explain why it is difficult to link autism to environmental factors, and what scientists know about how the environment influences autism risk.

What qualifies as an environmental risk factor?
The term ‘environmental risk factor’ is usually understood to mean the chemicals or pollutants a person is exposed to. But scientists use a broader definition: An environmental risk factor is anything that alters the likelihood of having a condition and isn’t encoded in an individual’s DNA.

Environmental risk factors for autism include being born prematurely, soon after an older sibling or to a mother with diabetes, for example. Over the past 15 years or so, scientists have investigated many of these factors to determine how they may contribute to autism. But there’s still little definitive information.

Why don’t we know which environmental factors increase risk for autism?
Studies of the environment’s link to autism have returned inconsistent results. For example, some studies suggest that taking antidepressants during pregnancy increases autism risk in the child others find no such link.

Most research on environmental risk comprises epidemiological studies, which identify associations between something in the environment and the likelihood of a diagnosis in large groups of people. But those studies do not demonstrate cause and effect.

For one thing, they are rife with what scientists call ‘confounding factors’ — variables that tend to travel together and make it difficult to pinpoint causal relationships.

What’s more, the causal relationships can be unclear. For example, we know that children with older fathers are more likely to have autism than those who have younger fathers. But we don’t know whether advanced paternal age itself increases autism risk or whether men who carry more genetic risk factors for autism, and perhaps display traits of the condition, tend to have children later in life.

Environmental factors are also often difficult to measure. Parents may be unaware of, or forget, what they and their child were exposed to. Or they may attach outsized importance to any detail they think could explain their child’s autism.

Which environmental risk factors for autism are well established?
The most widely accepted risk factors operate during gestation or around the time of birth. Various pregnancy and birth complications are associated with an increased risk of autism. These include preterm birth, low birth weight and maternal diabetes or high blood pressure during pregnancy. Scientists are not sure of the mechanisms underlying these associations.

The maternal immune system appears to play a role in autism risk. Infections, serious illnesses, such as a bad case of influenza, and hospitalizations during pregnancy are all linked to an increased risk of autism in a child. Women with autoimmune diseases, in which the body attacks its own tissues, are also at an elevated risk of having an autistic child. And animal studies suggest that certain immune molecules can alter gene expression and brain development in ways that may be relevant to autism.

Exposure to the drug valproate, which is used to treat bipolar disorder and epilepsy, in the womb is known to increase the risk of autism, as well as a variety of birth defects.

What other factors are scientists investigating?
Scientists are still trying to tease apart the effects of maternal antidepressant use during pregnancy from those of depression itself. One reason this issue has been difficult to settle is that if a parent has a brain condition, his or her child may carry shared genetic factors that increase autism risk.

Evidence that exposure to air pollution during gestation or early life increases a child’s risk of autism has grown more robust over the past few years. Still, many questions remain, such as which of the many components of air pollution might be involved.

Which proposed risk factors have been ruled out?
Despite the links between maternal immune factors and autism, routine vaccinations given during pregnancy, such as those against influenza and whooping cough, do not appear to boost autism risk.

Childhood vaccines are similarly in the clear. The research that purported to show a causal link was fraudulent and has been retracted, and no reliable evidence has ever emerged to support it.

Scientists have also exonerated smoking during pregnancy as a contributor to autism. Of course, smoking during pregnancy is harmful for many other reasons.

Are there any environmental factors that lower the risk of autism?
Scientists are trying to identify environmental risk factors for autism so that they can find a way to lower the risk. But the factors backed by the strongest evidence are not easy to modify.

Some studies suggest that taking vitamin D and vitamin B-9, or folic acid, supplements during pregnancy can decrease the baby’s autism risk. But the evidence is not definitive.

What are scientists doing to find out more?
New statistical techniques are helping scientists tackle confounding factors and draw more robust conclusions from epidemiological studies. Animal studies provide evidence about the mechanisms by which particular factors increase or decrease autism risk. And several efforts, such as the Environmental influences on Child Health Outcomes study and the Early Markers for Autism study, are tracking environmental exposures and risk factors in children, starting before birth.

What should parents and prospective parents do?
Families who are at high risk of having a child with autism — because they already have one child with the condition, for example — should consult with their doctor or a genetic counselor for specific recommendations. For most people, though, the general recommendations given to pregnant women (get a flu shot, take prenatal vitamins) are unlikely to cause harm and may even help.

It’s also important to remember that even for environmental factors that do appear to increase autism risk, the absolute risk of having a child with autism is small. For example, a large 2014 study of women in Sweden revealed that having an infection during pregnancy increases the risk of having a child with autism from 1 percent to 1.3 percent.


Modifiers in ASD

Genetic Modifiers

Though significant progress has been made in determining genetic causes of ASD, many aspects of how pathogenic variants regulate genetic susceptibility remain unknown. Individuals with the same variants can have widely heterogeneous disease presentations and levels of disability. Presence of second modulating variants that may interact with other susceptibility loci are one possible explanation of this heterogeneity. This “second hit” could be somatic – a phenomenon first proposed to cause disease by Alfred Knudson in the context of retinoblastomas – or in the germline, a “two-locus model” previously explored in conditions such as Hirschprung disease (Knudson, 1971 Fisher and Scambler, 1994 McCallion et al., 2003). To date, genetic evidence supporting a multiplex theory of autism has primarily been found for germline second-hits. Studies with CNVs will be discussed first, followed by a brief overview of known modulating SNPs. These investigations of how non-causative variants may modify the ASD phenotype are challenging to undertake, as few autistic individuals have the same pathogenic variants. In addition, there is not yet a complete understanding of which CNVs and SNPs are pathogenic in ASD.

One way to circumvent these issues is to investigate an autism subtype with a monogenic cause, such as Rett Syndrome. Artuso et al. (2011) used this strategy and identified 15 “likely” and 14 “unlikely” modulators of the RTT phenotype based on array comparative genome hybridization with eight RTT subjects. Another valuable approach is to assess monozygotic twins with a discordant phenotype. Several studies have assessed potential differences in CNVs or epigenetic regulation in discordant monozygotic twins, revealing potential methylation pattern differences in one case and anomalies in the 2p25.3 region in another (Bruder et al., 2008 Kunio et al., 2013 Rio et al., 2013). However, a study involving 100 twin pairs failed to find differences in CNVs that could explain the discordant phenotypes (Stamouli et al., 2018). The authors still acknowledge postzygotic mosaicism as a potential modifier and encourage more studies to help develop a clearer understanding of CNV modulating activity.

A handful of reports also exist of putative modifying CNVs in polygenic ASD cases with unrelated subjects. For example, Girirajan et al. (2012) found that children with two CNVs not known to be pathological were eight times more likely to be diagnosed with developmental delay than controls. In the same year, a study of SHANK2 pathogenic variants found abnormalities in both individuals with neuropsychiatric disease and controls, suggesting the presence of additional variants in order to cause disease. Three of the patients with de novo SHANK2 mutations were also found to have deletions of CHRNA7 and cytoplasmic FMR1 interacting protein 1 (CYFIP1) – both previously implicated in ASD – supporting a “multiple-hit” model of autism (Leblond et al., 2012). CHRNA7 was also suggested as a potential modifier in an earlier study by Szafranski et al. (2010). Barber et al. (2013) provided further support for a multiple-loci model of ASD upon finding that patients with 16p12.1 duplications had a more severe phenotype when a second large CNV was present. Included in these hypothesized modifier regions were genes G protein regulated inducer of neurite outgrowth 2 (GPRIN2) – previously implicated as a modifier in the study by Artuso et al. (2011) – and steroid sulfatase (STS), which was formerly thought to be non-causative (Li et al., 2010). More recently, an analysis of 20,226 patient records revealed 19 patients with CNVs in contactin 6 (CNTN6), a gene hypothesized to be involved in neurodevelopmental disorders including ASD (Repnikova et al., 2019). The authors were not able to find any significant genotype-phenotype relationships and concluded that CNV in CNTN6 were likely benign or modifying, but not causative of disease.

In addition to CNVs, there may be thousands of smaller pathogenic variants – such as SNPs and indels – that also modulate severity. For example, in a study of developmental delay, individuals that only carried a specific 16p12.1 microdeletion had a less severe phenotype than individuals with random second variants (Girirajan et al., 2010). One study of individuals with 22q11.2 deletion syndrome – all haploinsufficient for an mGluR network gene – found that 20% who were co-diagnosed with autism had second-hit pathogenic variants, while only 2% of 22q11DS individuals without autism had second hits (Wenger et al., 2016). Bonnet-Brilhault et al. (2016) assessed a family affected with ID and ASD due to NLGN4X pathogenic variants and found that individuals with ASD – but not ID or controls – had second-hit variants in glycine receptor beta (GRLB) and ankyrin 3 (ANK3). Additional evidence may exist, but GWAS and WES studies have tended to focus on causative susceptibility loci. Therefore, other variants which are not causative by themselves are not often emphasized or even reported. The emerging study of all types of genetic modifiers is a relatively recent development, and continuing advancements in sequencing technology, analyzing software, and expansion of databases should lay the framework for significant advancements in the near future.

Epigenetics and the Environment

Autism susceptibility is currently estimated to be 40�% genetic. Environmental factors – likely acting through epigenetic regulation as the major mechanism – presumably compromise the remainder of the risk. Hundreds of potential environmental factors have been suggested to contribute to risk, such as increased parental age (especially paternal), maternal complications or infections during pregnancy, or prenatal exposure to anticonvulsants (Rasalam et al., 2005 Kong et al., 2012 O’Roak et al., 2012 Ohkawara et al., 2015). In-depth reviews of these findings can be found elsewhere (Gardener et al., 2009 Chaste and Leboyer, 2012 Liu et al., 2016 Karimi et al., 2017 Modabbernia et al., 2017 Bölte et al., 2019). In this review, we will only discuss the epigenetic modifying effects of valproic acid – an anticonvulsant – as one example of the widespread modifications that an environmental factor can induce. Valproic acid has been hypothesized to modify gene expression through histone deacetylase inhibition activity and is sometimes used to induce an autistic phenotype in animal models (Kataoka et al., 2013). Examples of its far-reaching effects include apoptotic cell death in the neocortex, decreased proliferation in the ganglionic eminence, increased homeobox A1 (HOXA1) expression, abnormal serotonergic differentiation via Achaete-Scute family BHLH transcription factor 1 (ASCL1) silencing, disrupted serotonin homeostasis in the amygdala, dendritic spine loss, reduced prefrontal dopaminergic activity, and disruption of the glutamatergic/GABAergic balance (Stodgell et al., 2006 Dufour-Rainfray et al., 2010 Kataoka et al., 2013 Wang et al., 2013 Jacob et al., 2014 Takuma et al., 2014 Hara et al., 2015 Iijima et al., 2016 Mahmood et al., 2018).

In more thorough studies of the mechanism of action, Go et al. (2012) found that rats exposed to valproic acid in utero presented enhanced proliferation of neural progenitors and delayed neurogenesis by upregulating Wnt1 expression and activating the GSK-3β/β-catenin pathway, leading to macrocephaly. Another study found that valproic acid increased BDNF by two transcriptional mechanisms involving MeCP2 and tissue plasminogen activator (tPA). This increase in BDNF is proposed to alter neurite outgrowth, impairing synapse formation (Ko et al., 2018). Finally, Kolozsi et al. (2009) observed a downregulation of NLGN3 – a highly implicated autism risk gene involved in synapse formation – in both hippocampal and somatosensory cortex of valproate-exposed mice. Examples of other proposed environmentally modulated mechanisms of ASD risk exist, but the literature supporting valproic acid is an excellent example of the heterogeneous effects one environmental factor can induce. Further research is strongly needed to determine how the environment modulates ASD risk.

Clearly, epigenetics can have a profound impact on the transcriptome of an organism. Pathogenic variants in even one epigenetic-regulating gene or effects from the environment can cause widespread gene dysregulation. Epigenetic modulators can themselves be causative of disease, but they may also exacerbate or ameliorate the disease phenotype by influencing expression of risk genes. More genome-wide studies are needed to understand the common ASD epigenome, and whether certain epigenetic markings might be protective or detrimental to individuals who are genetically susceptible. In addition, more studies are needed to decipher epigenetics as a link between environmental risk factors and genetic susceptibility. There is a possibility that certain environmental factors could have protective epigenetic effects, providing potential avenues for therapy.

Sex-Linked Modifiers

It is well established that ASD affects males at much higher rates than females. The reasons for this are not yet completely clear. Some studies argue that differential expression between genders may result in an under-diagnosis of females, as males tend to present more external behavior (e.g., aggression or increased repetitive behavior) and females tend to present more internal behavior (e.g., depression and avoiding demands) (Werling and Geschwind, 2013). While this may contribute to the rates of diagnosis, other possibilities include that the female sex is protective and/or males are particularly vulnerable. This may be due to influence from hormones, genetics, or other unknown factors. The genetically heterogeneous nature of ASD makes it likely that all these elements are involved – sex bias varies drastically based on factors such as which CNVs are causative or which comorbidities are present, suggesting diverse means by which a sex bias may occur (Amiet et al., 2008 Polyak et al., 2015). Potential mechanisms of sex-specific modulation will be discussed briefly, although more thorough reviews are available elsewhere (Ferri et al., 2018).

Multiple studies argue that the female sex is protective toward ASD susceptibility (Robinson et al., 2013 Pinto et al., 2014). For example, the average mutational burden in diagnosed females is much higher than in males, suggesting that males have a lower mutational burden threshold (Jacquemont et al., 2014 Desachy et al., 2015). Another study by Robinson et al. (2013) investigated nearly 10,000 dizygotic autistic twin pairs and found that siblings of female probands had significantly worse symptoms than siblings of male probands. Many investigations have also found that unaffected mothers may carry the same mutation as their affected male children. One particularly well-documented example for this is the 15q11-13 duplication (Cook et al., 1997 Schroer et al., 1998 Gurrieri et al., 1999 Boyar et al., 2001). This region codes for GABAA receptors, which is supported by the observation of perturbed GABA signaling in ASD (Al-Otaish et al., 2018). The discovery that estrogens rescue ASD phenotypes in both zebrafish and mouse models of autism is an especially convincing piece of evidence for the female protective theory (Macrì et al., 2010 Hoffman et al., 2016).

It is also possible that the female sex is not protective, but males are particularly vulnerable. Three studies of gene expression patterns noted males generally had a higher expression of genes implicated in ASD, such as chromatin regulators and genes related to immune involvement (Ziats and Rennert, 2013 Shi et al., 2016 Werling et al., 2016). A study with rat models of ASD reported male-specific downregulation of MeCP2 leading to abnormal glutamate activity, providing another potential mechanism for male-specific vulnerability (Kim et al., 2016). Interestingly, multiple studies have found decreased levels of aromatase – an enzyme that catalyzes the conversion of testosterone to estradiol – in the brains of adolescent ASD individuals (Sarachana et al., 2011 Crider et al., 2014). Decreased aromatase has also been associated with decreased RAR-related orphan receptor A (RORA), an ASD-associated gene that is oppositely regulated by male and female hormones (Nguyen et al., 2010 Sarachana et al., 2011). Hu et al. (2015) found a much stronger correlation between RORA expression and that of its targets in the cortex of male mice relative to female mice, suggesting that RORA-deficient males may have greater dysregulation of genes than females.

Of course, there may also be a combination of female-specific protective and male-specific deleterious effects. For example, Jung et al. (2018) recently assessed sexually dimorphic traits in a CHD8 +/N2373K mouse model of autism. While male mice demonstrated abnormal social behaviors such as isolation-induced self-grooming, female behavior was similar to controls. Neuronal excitability was also enhanced in males and suppressed in females. Transcriptomes were distinct, with female mice revealing an enrichment for ECM molecules, likely providing a protective effect.

A likely mechanism of divergent modulation is from differential effects of sex hormones, which have been hypothesized to play an important role in ASD pathology for both males and females (Baron-Cohen et al., 2005, 2015 Whitehouse et al., 2010 Honk et al., 2011 Ferri et al., 2018). For example, testosterone and estrogen have been shown to have contrasting effects on the immune system (Lenz et al., 2013 Roved et al., 2017), which has been repeatedly shown to play a pathological role in ASD (Estes and McAllister, 2015 Koyama and Ikegaya, 2015 Kim et al., 2017 McCarthy and Wright, 2017 Nadeem et al., 2019). Schwarz et al. (2011) analyzed biomarkers from individuals with Asperger’s syndrome and found 24 male-specific and 17 female-specific hits, including many immune-related molecules. Spine density, another phenotype strongly implicated in autism (Comery et al., 1997 Irwin et al., 2001 Hutsler and Zhang, 2010 Durand et al., 2012 Takuma et al., 2014 Tang et al., 2014 Liu et al., 2017a, b Soltani et al., 2017), is also affected by testosterone (Hatanaka et al., 2015). Key molecules involved in neurotransmission such as GABA, glutamate, serotonin, and BDNF are all implicated in ASD and modulated by sex hormones (Kim et al., 2016, p. 2 Saghazadeh and Rezaei, 2017 Al-Otaish et al., 2018 Edwards et al., 2018 Ferri et al., 2018 Garbarino et al., 2018 Zieminska et al., 2018). It is not yet clear whether the majority of differences between male and female presentation of ASD arise from differential regulatory actions of sex hormones or from other modifiers, but the presence of a sexually dimorphic phenotype is well established. Future research will likely elucidate a clearer picture of the identity and mechanisms of sex-specific modifiers.


Evidence for converging molecular pathways

Several recent studies have suggested that in addition to convergent brain pathways, that there may as well be convergence at the level of molecular mechanisms in ASD. One class of such studies has asked whether putative ASD susceptibility genes are enriched in members for specific molecular or biological processes more than expected by chance. The value of this approach depends on the level of experimental support for the specific genes tested and the degree to which current pathway annotations represent reality [25, 68]. For genes identified within CNV this can be particularly problematic, as most known pathological CNV contain more than one gene and it is not expected that all genes within the CNV contribute to ASD, potentially increasing noise in this analysis. One recent study [69] reduced such background by using a new phenotype-driven method to group genes within high confidence de novo CNV [34, 69], identifying significant enrichment for several categories of genes, including axon outgrowth, synaptogenesis, cell-cell adhesion, GTPase signaling, and the actin cytoskeleton. These results replicate and extend earlier composite pathway analysis of putative ASD susceptibility genes compiled from the literature [68], and CNV pathway analysis in the Autism Genetic Resource Exchange (AGRE) and other cohorts [32, 36]. Still, these studies place ASD genes within a multiplicity of pathways, several of which are broad and do not necessarily demonstrate convergence on final common molecular processes in individuals.

In this regard, two recent studies use quite different systems biology approaches to provide a new perspective on the concept of molecular convergence. The first, an analysis of gene expression in post-mortem autism brain, provides the strong evidence for a shared set of molecular alterations in a majority of cases of ASD. This included disruption of the normal gene expression pattern that differentiates frontal and temporal lobes (consistent with an early developmental patterning defect), and two groups of genes dysregulated in ASD brains: one related to neuronal function, and the other to immune/inflammatory responses [49]. The neuronal function genes were enriched in genetic association signals, providing evidence that these changes were causal, rather than the consequence of the disease [49], while the immune/inflammatory changes did not show a strong genetic signal, implicating environmental or epigenetic factors instead. It is also notable that the several of the same biological pathways identified in this gene expression study overlapped with the pathway analysis of CNV described above. This analysis of post-mortem autism brain also showed down-regulation of several markers of GABAergic interneurons, suggesting potential inhibitory interneuron dysfunction. These results provide the first strong evidence for both a shared genetic and an environmental/epigenetic basis for ASD and the presence of an early developmental patterning defect. It is tempting to speculate that the abnormalities in cortical patterning and interneuron function provide a molecular basis for cortical-cortical and cortical-fugal disconnection, linking molecular abnormalities with anatomical, physiological and imaging findings.

The second study on molecular convergence in ASD identified protein interactors of known ASD or ASD-associated genes [70]. This interactome revealed several novel interactions, including between two ASD candidate genes, Shank3 and TSC1. The biological pathways identified in this study include synapse, cytoskeleton, and GTPase signaling, demonstrating a remarkable overlap with those identified by the gene expression and CNV pathway studies discussed above. This study differs from other genome-wide studies (such as mRNA expression) as it begins with known ASD genes and asks about their relationships. So although it is “ –-omic” in nature [71], it is not quite as unbiased as methods that survey the genome more agnostically. Despite the significant heterogeneity in ASD, these diverse studies identify several common areas of molecular convergence in ASD. Understanding how these pathways relate to individual differences now becomes an important research priority.


Seven Science-Based Facts on Which Researchers Agree

While it is possible to find someone out there who will disagree about virtually any statement regarding autism, the vast majority of experts do agree on the following seven points. While these points don't necessarily provide a clear path to prevention or cure, they do help point the way.

There Is More Than One "Autism"

About 25% of autistic people have digestive issues 25% have seizure disorders many have sleep problems. Recent findings suggest that the many different symptoms may actually indicate many different causes -- and thus many different "autisms." A massive study now underway at UC Davis's M.I.N.D. Institute is in the process of separating out different autistic phenotypes with the hope that this information will speed better understanding of causes and treatments.

Autism Has a Genetic Component

Autism is hereditary, in that children with autistic people in their family are more likely than other children to be autistic. Researchers are well on the way to finding genes that relate to autism -- but the jury is still out regarding exactly how such genes might function to create autistic symptoms. Sophia Colamarino, Science Program Director at Cure Autism Now, explains, "We’re talking about genes because they allow us to understand the biological origins of the problem."

There Is a Relationship Between Autism and Brain Structure

Recent brain studies show that autistic brains grow at an unusual rate between the ages one and two and then slow again to a normal rate of growth. Some imaging studies suggest that certain areas of the brain are larger than is typical. Research is ongoing to determine whether these differences in brain structure cause autism, are caused by autism, or are comorbid with autism and caused by something else.

There Is a Relationship Between Autism and Brain Activity

Recent brain imaging studies show that autistic people and typically developing people do not use their brains in the same way. Autistic people do not use their brains to "daydream" in the same way as most people, nor do they process information about faces in the same way. So far, while we know that this information is true, we don't know what causes these differences -- or whether these differences somehow cause autistic symptoms.

There Is a Relationship Between Autism and Brain Chemicals

Chemicals in the brain transmit signals which allow the brain to function normally. Sophia Colamarino explains: "Nerve cells communicate using electrochemical signals there is evidence from many different domains that the ability of the brain to transfer information may be defective." An understanding of which transmitters are problematic may lead to effective treatments.

Genes Probably Interact With Environmental Factors

It is likely that genetics and environmental factors interact to cause autism. As yet, there is no proof of which environmental or genetic factors are to blame. Says Dr. Croen, autism "You need some kind of genetic susceptibility then you have to be exposed to something which is elusive at the moment. This would be the impetus that sends you into autism."

No One Factor Causes Autism

It is unlikely that any single factor—vaccines, foods, or environmental toxins—is the cause of the steep rise in autism diagnoses. "To find clues about the cause," says Dr. Croen, "we have to do really large studies to look at different configurations of co-morbidities… see what’s unique about each separate group." New research will be addressing the questions "How do these circles overlap? What is the common thread?"


Is There A Strong Genetic Predisposition In Autism

For a while, the medical fraternity have been trying to answer a singular question: Is Autism Genetic? According to the latest research, scientists now believe that Autism is linked to a very strong genetic predisposition and is almost certainly hereditary in a majority of cases.

In a study that involved as many as 258 twins from a diversified ethnic and demographic background, the genetic influence on ASD (Autism Spectrum Disorder) was estimated to be anywhere between 74% to 98%.

Environmental and Genetic Make-up are the most commonly known causes of Autism

Some of the hereditary risk factors for Autism were also found to have a strong overlap with genes influencing less extreme or borderline autism symptoms that are available in the general population.

This recent study was conducted by the Institute of Psychiatry, Psychology & Neuroscience at King’s College, London. The paper has since been published in the JAMA Psychiatry journal.

Beata Tick, Lead Researcher, explains “The key finding out of our research was that the heritability of Autism Spectrum Disorder is much higher than we originally thought. By analyzing the results, we were also able to conclude that genetic factors may lead to a wide range of autistic symptoms and behavioral traits across the general population.

It is noteworthy that the results seem to indicate that genetic inheritance might well be among the key causes of Autism despite the dramatic increase in ASD prevalence over the last 20 years

The data source for this research was compiled from the TEDS (Twins Early Development Study) diversified population-based database. The research was funded by the Medical Research Council (MRC).

“A well-established approach, to clarify the extent of social, environmental and genetic influences in Autism, is to compare the commonalities between non-identical and identical twins”, says Professor Patrick Bolton, co-author and fellow member of King’s college.

Researchers believe that the ingenuity of this study lies in the fact that it included twins regardless of whether they had gone through a clinical diagnosis for Autism. This provided the theorists a holistic picture of the kind of influences that society, genetic makeup, and the environment has on the development of a child and how more subtle differences may manifest into pronounced autistic trends.

Their findings add more weight to the view that extreme manifestation of autistic traits and behaviors, observed in the general population, eventually leads to ASD.