Autism in a nutshell: the known causes, and why vaccines are not among them

In this post I will write about a very sensitive health-related issue: autism. I will summarize its features, focusing on potential causes and clarifying the autism-vaccines debate.

Let’s begin with an overview. Autism is not a single disease, but a spectrum of neuro-developmental disabilities that are difficult to identify before the age of 2 or 3 years, the age when the full range of behavioral symptoms has emerged in most cases. Autism spectrum disorders are characterized by impairments in social interaction and stereotyped behaviors (e.g., restricted interests and repetitive actions). Autism has a frequency of 0.7–1.1% in the population and it is four times more common in males than in females. Symptoms coexist with other psychiatric and medical conditions such as intellectual disability, epilepsy, motor control problems, attention-deficit/hyperactivity disorder (ADHD), tics, anxiety, sleep disorders, and gastrointestinal problems. A common feature in people affected by autism is an abnormal (too high or too low) response to sensory stimuli.

Huguet and colleagues, in 2013, published a paper from which I extrapolated the picture below. It shows the main symptoms of autism. The red line shows the severity of each symptom (lower at the center, higher at the periphery). Colors, instead, represent the combination of clinical features.

Untitled

The main cause of autism remains unknown, although nowadays it is clear that genetics and environment play important roles.

Genetic risk factors

Genetics’ role in autism was first showed by the recurrence risk in families and twin studies. For example, the recurrence risk in a family in which there is already one member affected by autism, is up to 20 times higher than in families in which no one is affected. So what happens to DNA to predispose for autism? The event is called “copy number variation”. This happens when a portion (of variable size) of chromosome is duplicated or deleted. This chromosomal region contains one or more genes, and altering the number of gene copies in a cell has significant consequences. Because each gene has a specific role, the consequence of the copy number variation depends on the function of the gene duplicated or deleted. Therefore, variation of the copy number of a specific gene can predispose to a disease rather than to another. Predisposition to autism has been proven for a list of genes that have a relevant function specifically in neurons (neuroligins, neurexins, and SHANKs), being involved in synaptic transmission (the communication system among cells in the brain). A long list of much smaller variations have been related to autism as well, and to understand what small variations are, I direct you to this other post I wrote.

Environmental risk factors

Advanced parental age is a well-established risk factor for chromosomal aberrations, such as advanced maternal age in Down syndrome, but also there are evidences of a role in etiology of psychiatric and neurodevelopmental conditions (e.g., bipolar disorder, schizophrenia, substance use disorders, ADHD, autism).

Fetal environment has been considered in the context of autism etiology. For example, severe maternal obesity and high-fat diet might impact on fetal and offspring neurodevelopment, and the risk is even higher in the presence of diabetes; maternal hypertension and high blood pressure can potentially alter fetal development and increase the risk of long-term vascular, cognitive, and psychiatric outcomes in the offspring; moreover, infections during pregnancy activate the maternal immune system, possibly causing numerous adverse neural effects in the developing fetal brain.

Several perinatal factors are thought to be associated with autism, although not as primary causes, but as co-cause of genetic predisposition. These factors include prematurity, cesarean delivery, low birth weight, low Apgar score (which measures health of the newborn child) and hypoxia (lack of oxygen).

Medication during pregnancy and/or lactation can represent a problem for the fetus or the offspring. Antidepressive and anticonvulsive medications (e.g., valproate, selective serotonin reuptake inhibitors) have been linked to autism.

Smoking and alcohol increase the risk of developing autism. Smoking exposes a developing fetus to thousands of harmful chemicals and oxygen deprivation, with potential consequences to fetal brain. Ethanol consumption during pregnancy can trigger multiple forms of neurodevelopmental damage, including fetal alcohol syndrome in cases of heavy drinking.

If a pregnant woman does not eat a proper diet, this can adversely impact developmental outcomes. Deficiencies in vitamin D, zinc and copper during early fetal development interacts with other risks, possibly contributing to the etiology of autism; instead contrasting results have been collected for iron deficiency.

Toxic exposures (air pollution, heavy metals, pesticides, organic pollutants) demonstrated neurotoxicity, and this candidates them as risk factors for autism.

Autism and vaccines

Let’s make it short: vaccines do not cause autism, and there are scientific studies that prove it.

First a short, necessary introduction. In science, there are two main kinds of studies used to verify if two events are connected: case-control and cohort studies. Case-control studies are used to identify factors that may lead to a medical condition by comparing subjects who have that condition/disease (“cases”) with patients who do not have the condition/disease but are otherwise similar (“controls”). Cohort studies are longitudinal studies that sample a cohort (a randomized group of people who share a feature of interest) and perform repeated observations of the same variables at intervals over an established period of time. Taylor and colleagues, in 2014, went through scientific literature to collect all case-control and cohort studies that had been performed to investigate possible correlation between vaccines and autism. 5 case-control studies (for a total of 9920 children) and 5 cohort studies (for a total of 1,256,407 children) were included in the analysis. In statistics, odds ratio is used to measure the correlation between two events, and it expresses the probability of event A to happen in the presence of the event B compared to the probability of the same event A to occur without the event B. So is the probability to develop autism higher among vaccinated children, compared to non-vaccinated? All studies demonstrated that there is no correlation between autism and vaccines. In detail, no correlation was found between autism and measles, mumps, rubella (MMR) vaccine, or thimerosal-containing vaccines such as the diphtheria, tetanus, pertussis (DPT or DT) vaccine, or mercury (a non-toxic derivate is present in some vaccines). About substances contained in vaccines (such as mercury and thimerosal), I recommend you to read my post in which I describe the topic in detail.

So there is nothing more to say, other than “vaccines do not increase the risk to develop autism”.

If you have any question, curiosity or doubt, write it in the comments, and don’t forget to share this post with your friends. Let’s fight fake news by spreading correct information!

References

Devlin B, Scherer SW. 2012. Genetic architecture in autism spectrum disorder. Curr. Opin. Genet. Dev. 22: 229–37

Elsabbagh M, Divan G, Koh YJ, Kim YS, Kauchali S, et al. 2012. Global prevalence of autism and other pervasive developmental disorders. Autism Res. 5: 160–79

LeBlanc JJ, Fagiolini M. 2011. Autism: a “critical period” disorder? Neural Plast. 2011: 921680

Ozonoff S, Young GS, Carter A, Messinger D, Yirmiya N, et al. 2011. Recurrence risk for autism spectrum disorders: a Baby Siblings Research Consortium study. Pediatrics 128: e488–95

Janecka M, Mill J, Basson MA, Goriely A, Spiers H, Reichenberg A, Schalkwyk L, Fernandes C (2017) Advanced paternal age effects in neurodevelopmental disorders-review of potential underlying mechanisms. Transl Psychiatry 7:e1019

Bölte, S., Girdler, S. & Marschik, P.B. Cell. Mol. Life Sci. (2018). https://doi.org/10.1007/s00018-018-2988-4

Taylor LE, Swerdfeger AL, Eslick GD. (2014) Vaccines are not associated with autism: An evidence-based meta-analysis of case-control and cohort studies. Vaccine, Volume 32, Issue 29, Pages 3623-3629.

Huguet G, Ey E, Bourgeron T. (2013) The Genetic Landscapes of Autism Spectrum Disorders. Annual Review of Genomics and Human Genetics. Vol. 14:191-213.

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