One of my resolutions for this new year is to put a bigger effort into science outreach. That's why I decided to adjust my aims and changed the topic and format of this blog accordingly.
I also started a new account on Instagram for sharing approachable science news, ideas and articles about brain, development and mental health. https://www.instagram.com/brainhabit/
The same topic will be covered in a blog post here at the end of the week, wrapping up on everything I shared during the week and citing references.
For this first week of 2021, I decided to start with the main topic of my research, which is Autism Spectrum Disorder (ASD). As a researcher in the autism field, I would like to help people know more about ASD, its origins, manifestation and development. It is a huge field of research, so you might understand that there is a lot to say. Here, I will introduce ASD starting from its diagnostic definition and will provide a quick overview of the current ideas in terms of possible causes, leaving more detailed descriptions and deeper discussions to the coming weeks.
But let's start with the definition:
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by challenges in communication and social interactions, by the presence of restricted and repetitive patterns of behaviours and interests, and by alterations in sensation.
ASD is a neurodevelopmental condition present in about 1.9% of the population, with about 1 child in 54 children diagnosed with ASD.
The term spectrum has been introduced in 2013 with the DSM-5 (fifth version of the diagnostic manual of mental disorders) as an umbrella term including what we used to recognise as autistic disorder, Asperger's disorder, or pervasive developmental disorder not otherwise specified. Apart from diagnostic details, I personally like the use of the word spectrum because it gives the idea of a continuum, that perfectly fits with the high level of variability of autism in its origins and manifestations in different people. There is no one single autism but every person with ASD has a unique combination of strengths and challenges. Thus, a person with ASD may experience serious challenges and need help and support throughout his/her life, but another person may be very highly skilled, need little extra help or be fully independent.
We know that there is no one single cause of autism. Autism is viewed, in fact, as a multifactorial disorder, which means it develops from multiple genetic and environmental influences. These influences, and their interaction, increase the probability that a child develops autism.
There is a difference between influence and cause. Some children may have a modified gene or a certain level of common genetic variation associated to autism, but not show the clinical manifestation of autism (they are not diagnosed with autism). Similarly, some children may be exposed to certain environmental risks and not develop autism. It is the complex and unique interaction of these different influences to lead to the clinical observation of autism.
We identified many different genes, as well as hundreds of genetic variants (single differences in the DNA between two people), both as common and rare variants, that contribute to the development of autism by impacting the regulation of fundamental processes of early brain development, such as the organization of brain cortex, structure and function of synapses (connections between neurons that allow these brain cells to communicate between each other), structural and/or functional connectivity of the brain.
On the other hand, we can list gestational diabetes, prenatal drug exposure, preterm birth, congenital infection and neonatal hypoxia (periods of oxygen deprivation to the baby's brain) conditions among environmental and medical risk factors.
The wrong idea that vaccines cause autism has spread in recent years because of the unfortunate correspondence in timing between autism diagnosis and a child’s vaccination. However, there is no scientific support for this. Researchers in the autism field have largely investigated the potential link between childhood vaccinations and autism in the last two decades. Results are clear: vaccines do not cause autism!Check this link for further scientific info on vaccines and autism:
https://www.healthychildren.org/English/safety-prevention/immunizations/Pages/Vaccine-Studies-Examine-the-Evidence.aspx?fbclid=IwAR3tbvoA9moN9qMJC_LdpxkJT3msIMg_mmIcCJ2eOlLZeSRqsasvjaDxS0E
The causes of Autism Spectrum Disorder (ASD) remain largely unknown, yet research has shown for decades a high genetic contribution to ASD, with an estimated heritability of 80% or higher.
It all started with family studies, namely the observation of how ASD runs in families and in particular the comparison of identical vs. fraternal twins. Studies in molecular genetics have then identified rare and penetrant mutations in more than 100 genes in approximately 10–25% of people with ASD. With the development of more recent technologies, we are now able to investigate more detailed mutations in the DNA of people, in particular variations of single nucleotides (single nucleotide polymorphisms: SNPs; where nucleotides are the building blocks of the DNA). Through these technologies, in the so-called genome-wide association studies (GWAS), we have found that multiple common genetic variants contribute to the origin of ASD.
This is why we consider ASD a polygenic condition, because many different genes are involved and overall the genetic landscape of ASD is shaped by a complex interplay between common and rare variations, which is most likely different from one individual to another.
In the general population, one individual carries on average 3 million genetic variations in comparison to the reference human genome sequence. More than 95% of these variations are the so-called common variants, shared with more than 5% of the human population.
The contribution of common variants is important, but there is no specific genetic code that causes the development of ASD. We have found more than 1000 SNPs that are each one associated with a little increase in probability of developing ASD, but in different combinations and in interaction with the environment these can lead to a significantly higher probability of developing ASD.
We know that a combination of genetic and environmental factors contributes to the development of ASD. Similar to what we observed in genetics, a broad range of environmental factors have been identified as increasing likelihood of developing ASD, but their individual effects tend to be small.
Environmental factors can have a major impact on molecular and cellular systems, and directly interact with the genome through what we call epigenetics. For instance, environmental factors can affect the quality and quantity of gene expression (how a gene is decoded and its instructions are actually followed in the cell of a person) without changing the DNA sequence. Examples of epigenetic mechanisms are changes in DNA methylation, changes in histone proteins (the storage packaging of DNA), and expression of noncoding RNAs (in simple terms, postal and translation services between DNA and the protein world). This way, environmental influences can be transferred to the next generation through epigenetic changes.
You may ask now: how can the environment alter development of my baby? Well, think about external factors that can change the instructions while building up the new baby during pregnancy. This is what happens when the expression of developmental key genes in critical periods of embryo formation is altered by environmental factors through epigenetics.
Here is a list of possible environmental influences on ASD development that have been identified through research in the last two decades:
Advanced parental age (particularly paternal age above 35). This is probably because of de novo mutations in germline cells (eggs and sperm), epigenetic changes in gene expression, or changes in immune system function affecting development of the nervous system of the baby during pregnancy.
Physical, mental and psychological health of parents may impact a child’s development by affecting their behaviour towards their child.
Emotional stress, particularly for mothers during pregnancy, can have a negative effect on the development of the baby.
Increased level of cytokines and excessive activation of the immune system in mothers can affect neural development of embryos and infants.
Depression of mothers during pregnancy, because antidepressants taken during pregnancy can pass through placenta and directly affect the development of the baby.
Exposure of pregnant mothers to chemicals such as pesticides, air and water pollutants, and heavy metals and other chemicals can have a negative effect on the development of the baby through epigenetic alterations of gene expression and neurodevelopmental processes such as changing neuronal migration (how the new brain cells take their position to do their job).
Similar exposure to chemicals of newborn babies through air pollution, but also from materials of toys, clothing, cutlery, baby bottles, etc. [BE AWARE of NEUROTOXINS! check #happylittlehabitatseries from a lovely colleague, Maheen, on https://www.instagram.com/happy_littleminds/]
The quality of mother–infant interactions during the postnatal period has great importance! Cuddles, kisses and the emotional bond between mother and baby is fundamental for the correct development of the brain, its connections and signaling pathways of some hormones such as dopamine, oxytocin, and serotonin. Have heard all unwanted suggestions of people who tell mothers not to hold their babies too much, or not to sleep with them, or to let them cry out themselves, etc etc otherwise the baby will be spoiled? Well, these suggestions should be simply ignored! There is extensive research on that, and science supports the exact opposite!
Mothers using drugs, too much or dangerous medications, drinking alcohol (half a glass per day can be dangerous too, yes!) or smoking (even passive smoking) during pregnancy can have serious adverse effects on the baby’s health. For instance, that may cause fetal hypoxia and affect fetal brain development.
Extreme prematurity or very low birth weight, and any birth difficulty leading to hypoxia.
Pregnancy obesity (>90 kg) and excessive weight gain during pregnancy are significantly associated with the incidence of ASD.
Some studies have also found an association between prolonged exposure to elevated temperature during pregnancy and ASD development.
Socio-economic status of the family can also have an effect, for instance through access to services during pregnancy and early development of the baby, but also for associations with stress in mothers, and other indirect effects on the environment in which the baby grows up.
The increase in the number of ASD diagnoses in the last few decades could partially be explained by better mental health care coverage, less stigma, greater awareness, and altered diagnostic criteria. However, it might also be partially related to parallel changes in environmental factors, such as the trend of increasing parental age at child birth and the viability of prematurely born infants.
Further reading
Amiri, M., Lamballais, S., Geenjaar, E., Blanken, L., El Marroun, H., Tiemeier, H., & White, T. (2020). Environment-Wide Association Study (En WAS) of Prenatal and Perinatal Factors Associated With Autistic Traits: A Population-Based Study. Autism research : official journal of the International Society for Autism Research, 13(9), 1582–1600. https://doi.org/10.1002/aur.2372
Karimi, P., Kamali, E., Mousavi, S. M., & Karahmadi, M. (2017). Environmental factors influencing the risk of autism. Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences, 22, 27. https://doi.org/10.4103/1735-1995.200272
Vermeulen R, Schymanski EL, Barabási AL, Miller GW. The exposome and health: Where chemistry meets biology. Science. 2020 Jan 24;367(6476):392-396. doi: 10.1126/science.aay3164. PMID: 31974245; PMCID: PMC7227413.
Bölte, S., Girdler, S., & Marschik, P. B. (2019). The contribution of environmental exposure to the etiology of autism spectrum disorder. Cellular and molecular life sciences : CMLS, 76(7), 1275–1297. https://doi.org/10.1007/s00018-018-2988-4
Bourgeron T. Current knowledge on the genetics of autism and propositions for future research. C R Biol. 2016 Jul-Aug;339(7-8):300-7. doi: 10.1016/j.crvi.2016.05.004. Epub 2016 Jun 8. PMID: 27289453.
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