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Is There a Relationship Between Serotonin and Autism?

by Molly Shaw Wilson MS OTR/L BCP November 14, 2019

Serotonin & Autism Blog Post

Autism is on the rise and scientists are narrowing down some potential causes as they research this developmental condition. According to numbers published by the Center for Disease Control (CDC) in 2018, approximately 1 in 59 children are diagnosed with autism. This statistic represents a 15% increase in autism prevalence as compared to numbers from 2016.

While boys are 4 times more likely to be diagnosed as compared to girls, there is progress in identifying the condition in females, who do not always fit the stereotypical picture of autism that boys may.

Autism is identified by three key components of behavior:

1. Persistent deficits in social interaction
2. Deficits in communication, symptoms often present before age 3
3. Restricted repetitive patterns of behavior, interests or activities (in 2 or more of the following):
    • Repetitive or stereotyped motor movements, use of objects or speech
    • Insistence on sameness, inflexibility with routines, ritualistic patterns of behavior
    • Restricted, fixated interests that are abnormal in intensity or focus
    • Hyper or hyporeactivity to sensory input

    While we do not know specifically what causes autism, science has helped to narrow down some of the risk factors, both genetic and environmental (non-genetic).

    Autism tends to run in families, and there are risk factors such as parental age, space between pregnancies, and some pregnancy/birth complications. There is no evidence that vaccines cause autism.

    There are comorbidities of medical symptoms with autism, especially gastrointestinal dysfunction. Scientists are looking at linking the severity of autism symptoms with the severity of gastrointestinal difficulty, highlighting the gut-brain connection.

    They are looking at serotonin and a disordered serotonin transporter (SERT), and where the breakdown is in the gut for individuals with autism. Some scientists suggest a mechanistical link between vitamin D and serotonin concentrations and the rise in autism.

    What is serotonin?

    Serotonin (also known as 5-hydroxytryptamine or 5-HT) is a chemical found in the body that has involvement in a variety of everyday functions. Widely known to boost emotions and contribute to overall happiness and wellbeing, serotonin is found in 3 areas of the body: in the brain, in the bowels, and in the blood.

    Serotonin is a neurotransmitter, is a type of chemical messenger which transmits signals across a synapse – the space between two nerve cells. Its function in the digestive system is to stimulate the muscles of the intestines. In the blood, it is responsible for shrinking and expanding vessels.

    sleep wake cycle

    Serotonin has a big job in the human body. It contributes to the regulation of sleep and wake cycles and the internal clock of the body. It has involvement in appetite, emotion, motor function, sexual desire and cognition. It helps with bone health, blood clotting, and even nausea.

    Most of us remember that there is a link between low serotonin levels and depression, although it’s a classic “chicken and egg” story. It is still unclear which came first – if low serotonin causes depression or if depression lowers the levels of serotonin in the body. Antidepressant medications work by increasing the levels of serotonin in the neurons, at the junction where communication between cells happens.

    The link to autism

    There is a long-history in identifying differences in serotonin levels in individuals with autism as compared to the rest of the population. More than 60 years ago, a study identified high levels of serotonin in the blood of 6/23 subjects. That finding in ratio has been repeated in many studies since then – about 1 in 4 individuals with autism have high blood serotonin levels. Over the years, science has looked at the use of antidepressants as a treatment for autism, but it has yielded mixed results.

    In the meantime, scientists are examining the link some more. They know that the blood serotonin levels are controlled by a transporter that moves serotonin from the gut (where it’s made) to blood cells. These levels have a genetic link, as they are inheritable.

    People with autism have a variant in their gut serotonin transporter which boosts the amount of serotonin into the blood. Conversely, individuals with autism have lower levels of serotonin in the brain than neurotypical individuals. Where serotonin is acting as a transmitter, there are less available amounts to carry messages across the synapse between neurons. It is here that antidepressants have been thought to help.

    Some research suggests that the reason for the “upside-down” levels of serotonin in individuals with autism (high in the blood, low in the brain) is because of low vitamin D. When adequate amounts of vitamin D are synthesized, it increases serotonin in the brain and decreases it in the peripheral tissues. This imbalance may contribute to abnormal brain development and autistic-like behavior.

    The issues with vitamin D and serotonin levels may also help to explain some of the gender differences in autism rates. The brains of boys may be more susceptible to decreased levels of vitamin D, putting them at higher risk for autism. The female sex hormone estrogen can increase the expression of tryptophan hydroxylase TPH, which helps to synthesize serotonin. This can, in essence, protect the female brain from vitamin D deficiency, accounting for the heightened incidence of autism in boys.

    Studies in rodents

    Mice with high blood levels of serotonin often demonstrate autistic-like behaviors. In utero, mice exposed to high levels of serotonin in the brain, showed changes in the brain region that is responsible for whisker movement – this area is responsible for social difficulty and repetitive behavior.

    In a 2013 study out of Stanford found that oxytocin may stimulate serotonin release in mice and that light exposure can facilitate more social behaviors. In observing mice exposed to a light source, their interactions around sniffing and grooming markedly increase, signifying more socialization. It was only sustained for the period of light exposure though, behaviors returned to previous levels when the light was turned off.

    Another 2018 study looked at the active ingredient in the recreational drug popularly known as ‘ecstasy’. The active ingredient in the drug is known as 3,4-methylenedioxymethamphetamine (MDMA). It has the potential to raise serotonin levels in the brain, which can ease the social anxiety that often comes with autistic symptoms. This is not without risk though. The United States federal government classifies ecstasy as a schedule 1 controlled substance which indicates that it has no medical value and is very risky for abuse.

    At Stanford, researchers are looking at mechanisms to alter the effects of hyperactivity associated with the drug. Their initial results in testing with mice injected with MDMA show that the animals are choosing to spend more time in controlled chambers with another mouse than with objects (a measure of increased socialization). An interesting finding that they have made when comparing mouse behavior is that although prosocial characteristics seemed to have been altered, its properties of reward did not. This means that although the mice were more social, it wasn’t necessarily a rewarding experience for them.

    Studies in humans

    About 10 years ago, the medical and scientific community began to look at antidepressants as a treatment for autism, in hopes that increasing serotonin in the brain may help to reduce the repetitive and irritability symptoms. Researchers used Prozac (fluoxetine) in clinical trials to block the reabsorption of serotonin into neurons, thus increasing the amounts available in the brain. Outcomes were largely ineffective, and science is suggesting new methods to allow for increased serotonin, rapidly activating serotonin receptors.

    autism and serotonin

    Last year, the journal CNS and Neurological Disorders – Drug Targets published a study that links serotonin metabolism and neuro-immune response to the severity of subtypes of autism spectrum disorders.

    Through the measurement of serotonin and tryptophan levels as well as different metabolic factors in the blood, scientists were able to attribute characteristics of intellectual and developmental disabilities, autism and Asperger’s. These markers are important for future research of autism and other childhood disorders.

    In 2018 the Saudi Medical Journal released information about an Iraqi study that involved 60 boys with autism. Researchers measured serotonin and serotonin transmitters (SERT) in the blood of patients. Their findings allowed for correlation between the severity of autism symptoms and the biomarkers of serotonin and SERT. These outcomes may lead the medical community to look at using serotonin levels in diagnosing and monitoring the development of the disorder.

    Scientists have studied the link between behavior and diet in adults with autism. When subjects have consumed a diet of foods low in tryptophan, their symptoms of autism worsen – repetitive behaviors and irritability increases. Brain studies reveal disordered activity in the regions that deal with processing, which can link serotonin to influence social behavior in adults with autism. Other brain studies in children with autism suggest that they produce lower levels of serotonin in the brain, and in other studies, too little serotonin binds to receptors in the brain.

    A study in Child and Adolescent Psychiatry shows some genetic links to serotonin levels in the blood and its heritable qualities to a baby from parents. Whole blood serotonin levels (WB 5-HT) are increased in children with autism by more than 25% as compared to their neurotypical peers. Science is linking maternal levels of WB 5-HT as influential in fetal development. Findings correlate these maternal levels in the blood with non-verbal IQ scores and adaptive functioning in children.

    Although the study doesn’t offer any transferrable outcomes to individuals and families with autism at the moment, it does offer some guidelines for long-term studies to look at this further, and some insight to guide research with mice to better understand the mechanism in the blood serotonin and its genetic qualities that influence symptoms of autism.

    What about fetal development?

    Science is unclear about fetal levels of serotonin and if they can be influenced to prevent autism. Generally, it is recommended that women avoid antidepressants during pregnancy, but the evidence to support that taking the drug increases the risk isn’t strong. Research can’t separate genetic factors that influence family history of depression (which are hereditary risks for autism) from the effect of the mother’s use of an antidepressant in utero on her baby.

    There is research to support vitamin D supplementation during pregnancy and early childhood – there are varying levels of recommended intake during these periods, some studies supplemented up to 4000IU (most doctors don’t recommend higher than 2000 IU). There are regulatory mechanisms in vitamin D responsible for serotonin synthesis and fetal levels come solely from the expectant mother. In addition to helping with serotonin production, vitamin D supplementation helps to lower birth defects and other pregnancy complications.

    Treatments

    We know that there is no cure for autism, but there are treatments for symptom management to help individuals with this life long developmental disorder.

    In addition to therapies and educationally based services, there are treatments that can help with serotonin levels, which may also improve some of the medical complications of autism (especially in the gut) and other behavioral implications.

    For the general population, serotonin can be increased by improving one’s mood, increased exposure to light, increased exercise and dietary changes. Although it needs further research, it is thought that serotonin levels can be influenced by diet, including taking supplements. Serotonin levels can’t be increased by eating serotonin rich foods (like bananas), because it doesn’t cross the blood/brain barrier during digestion. Diets rich in those foods that contain high levels of tryptophan are known to increase mood and brain function, though. Tryptophan helps the body to produce more serotonin. Protein-rich foods with high levels of tryptophan include turkey, eggs, salmon, eggs, and many soy-based foods.

    Supplementing with foods high in tryptophan can lead to increased levels of serotonin in the brain, as well as help to reduce social anxiety. Combining supplementation of tryptophan with vitamin D will help regulate the serotonin production to the brain while limiting it in the gut. Be cautious of 5-HTP (5-hydroxytryptophan) intake because of its involvement in converting serotonin in the gut, this is linked to increased inflammation in the gastrointestinal system. With the support of a nutritionist, look at vitamin B6, folate, iron, and omega-3 fatty acids intake as they also are factors in serotonin synthesis and can also contribute to improvement in some of the symptoms of autism.

    Raising vitamin D intake may show improvement in gut-related issues for individuals with autism. Excess serotonin in the gut can contribute to immunological changes and gastrointestinal inflammation. Ames and Patrick out of the University of California suggest that raising vitamin D concentrations can help alleviate GI inflammation by lowering serotonin levels. Vitamin D supplementation is recommended during pregnancy so that a mother can pass this on to her developing fetus. Expectant mothers should consult their obstetrician about the appropriate levels for intake.

    Antidepressants are in a drug class knows as SSRIs (selective serotonin reuptake inhibitors) and can help to increase the amounts of available serotonin at neuronal synapse, so that messages can be carried to neurons. They can make serotonin accessible at the synapse for longer periods of time, to increase the chances that it will bind and carry messages across for smoother transmission. Studies to date have shown some mixed benefits in adults with autism though, it has not been studied with children. Science is looking at further research in changing the mechanisms of SSRIs work in the brain, in hopes this will be a better option for individuals with autism in the future.

    In summary

    Although we don’t yet have definitive information about the cause for autism, science is narrowing things down and getting closer to understanding the intricacies of this developmental disorder.

    We are starting to understand the genetic link involved in passing down some of the heritable qualities of autism, and looking at environmental influences in utero. Serotonin is one factor that researchers link to about 25% of autism cases, and the research continues. There are biological markers around serotonin and SERT that link to autism. We know that individuals with autism have higher blood level serotonin and lower levels in the brain. It is linked to the gastrointestinal system and dysfunction in the gut correlates to the severity of the disorder.

    While there are varied outcomes and recommendations in using serotonin treatments for autism, they are making progress with linking the two, and we should be watching for future research. Scientists have replicated changes in serotonin in the brains of mice to their behavioral. Dietary changes have offered some symptomology relief for some, and we are considering those influences on fetal development related to autism.

     


    References

    https://www.spectrumnews.org/news/serotonins-link-autism-explained/

    https://www.spectrumnews.org/news/distinct-brain-pathway-underlies-ecstasys-social-effects/

    https://www.spectrumnews.org/news/study-revives-serotonin-target-autism-treatments/

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6118182/

    https://www.sciencedirect.com/science/article/abs/pii/S1043661818320942

    https://www.sciencedirect.com/science/article/abs/pii/S0890856718317726
    https://europepmc.org/abstract/med/30033880
    https://onlinelibrary.wiley.com/doi/full/10.1111/j.1469-7610.2010.02277.x

    https://www.ihcan-mag.com/solving-autism-vitamin-d-and-serotonin-synthesis/



    Molly Shaw Wilson MS OTR/L BCP
    Molly Shaw Wilson MS OTR/L BCP

    Molly Shaw Wilson MS OTR/L BCP is a board-certified pediatric occupational therapist with 16 years experience. She owns a private practice and provides service in homes, community and school settings, as well as her outpatient sensory clinic.

    Molly enjoys working with young children and their families, focusing on parent-child interactions and home routines. She is a regular contributor to a parenting blog about typical development. Her professional interests have stemmed from her certificate work in assistive technology, hippotherapy practice, and consultation to a nature-based program in New Hampshire.

    To find out more about Molly, please visit her website at www.trainingwheelsnh.com


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