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Autism Coach

Neurotransmitters and Autism

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Neurotransmitters are chemicals that transmit signals from one neuron to another.  The levels of neurotransmitters tend to be skewed in individuals within the autism spectrum.  This article starts with an explanation of how nerves communicate, the gut/brain neurotransmitter connection, and discusses specific neurotransitters that current research has found to be of relevance to autism.  

How Nerves Communicate

Before understanding neurotransmitter problems, you need to understand how your nerves actually communicate with one another. 

Like the wires in your home electrical system, nerve cells make connections with one another in tiny circuits called neural pathways. But unlike the wires in your home, these nerve cells do not touch, but instead come very close together at a synapse (pictured below). At the synapse, the two nerve cells are separated by a small gap, which is called a synaptic cleft. The sending neuron is called the presynaptic cell (in this case, an axon), while the receiving neuron is called the postsynaptic cell (in this case, a dendrite).


In a one-way direction across the synapse from the presynaptic cell to postsynaptic cell, your body sends chemical messages using neurotransmitters. This is called synaptic transmission.


Serotonin Transmission Example

The pre-synaptic cell makes serotonin from an amino acid called tryptophan and then packages the serotonin into vesicles located in end terminals. When a signal called an action potential arrives from your brain, that signal passes down presynaptic cell into the end terminals.

At this point, when the signal arrives, the serotonin is released and passes across the synaptic cleft, where it binds with special proteins called receptors on the outside of the postsynaptic cell. If enough serotonin binds to receptors, a threshold level is reached, and the action potential will be propagated in that cell and move on to the next cell. In the case of something like your muscles moving, the action potential would eventually reach skeletal muscle fibers and cause a contraction.

So that the nerve doesn’t remain in a constantly “turned on” state, the remaining serotonin molecules in the synaptic cleft then get destroyed by special enzymes in the cleft called monoamine oxidase (MAO) and catechol-o-methyl transferase (COMT). Some serotonin also gets taken back up by specific transporters on the presynaptic cell (this is called “reuptake”). All of this enables the nerve signal to be turned “off” and readies the synapse to receive another action potential.


Excessive Levels of Excitatory Neurotransmitters and Lower Levels of Calming Neurotransmitters in Autism

In most individuals within the autism spectrum, research indicates there are excessive levels of the excitatory neurotransmitter, glutamic acid.  Glutamic acid normally converts to glutamine in neurotypical individuals, but this metabolic pathway appears to be disrupted in individiuals with autism, resulting in high levels of glutamic acid and low levels of glutatmine.  The excessive levels of glutamine cause neurons firing excessively.  

MAO, which is present within the cytoplasm of neurons, breaks down neurotransmitters to form highly reactive aldehyde intermediates. The dopamine metabolite DOPAL (3-, 4-dihydroxyphenylethanol) is one of the reactive aldehyde intermediates formed by MAO and is a potent neurotoxin. Studies have found that Parkinson's-like brain lesions can be induced with DOPAL and that the cognitive impairment seen has similarities to autism.

Researchers are now finding that neurotransmitters not only are released from the synapses but can also leak directly out of the neuron vesicles directly.  This leaking process is a significant source of neurotransmitters degraded by MAO and also of neurotoxin formation.

In a neurotypical individual, the active release of neurotransmitters and subsequent reuptake contributes only a very small fraction (<2%) of the neurotransmitters come directly from the vesicles and are metabolized by MAO to form neurotoxins. However, when neurons are overexcited the ratio changes to >60% of the neurotransmitters originating from the synapses and <40% are from the non-specific leaking of vesicles. This high rate of firing and leaking of neurotransmitters from vesicles significantly increases the formation of toxic metabolites within the neuron and cause neurological damage.  Individuals within the autism spectrum also tend to have lower levels of calming neurotransmitters that can inhibit the over-firing of neurons.

If there is excessive firing of neurons, it would also stand to reason that the MAO would be depleted and there would be lower levels of MAO.  MAO is required to degrade the neurotransmitter, serotonin.  Individuals within the autism spectrum can have too much or too little serotonin. Serotonin converts at night to melatonin, the neurotransmitter that induces sleep.

The Gut/Brain Neurotransmitter Connection

The intestinal tract acts as a second brain that automatically controls digestion of food.  As such, it actually uses and produces neurotransmitters. 

Individuals within the autism spectrum have a chronic inflammation/infection of the intestinal tract. This inflammation results in damage to the lining of the intestinal tract, which is normally lined with hair-like villi cells that absorb food.

In the intestinal tract of a leaky, inflammed gut, the villi are often damaged or reduced in number and there are lesions exposing the layer of the intestintal tract that is under the villi, where the immune system cells live and protect the body against foreign invaders entering the body through the digestive tract.  If the villi are damaged and food proteins touch the inner immune system layer, the immune system can react as if the food is an invader, resultingn in food allergies. 

If the villi aren't digesting all the food and excessive amounts of it pass poorly or undigested through the intestinal tract, this poorly digested food becomes a breeding ground for pathogenic bacteria, which then form colonies in the gut.  The beneficial probiotics, which help to digest food and produce vitamins for the body are fewer in number, and the pathogenic organisms produce neurotoxins which leak into the bloodstream and pass through the bloodstream into the brain, skewing neurological development. 

Dr. Derrick MacFabe

These intestinal colonies of pathogenic organisms often produces proprionic acid as a by-product.  London researcher Derrick McFabe and his team found an elevated level of propionic acid changes immune function and tinkers with how the body breaks down fat and absorbs energy.  Excessive levels of proprionic acid actually lowers cholesterol and blood pressure - these can be diagnostic markers that would indicate this is an issue.  Proprionic acid is used in processed foods as a preservative and is found at high levels in certain cheeses, such as Swiss and cottage cheese.

When given to rats, the proprionioc acid replicated autistic-like behaviours — the rats became hyperactive, anti-social and more interested in objects instead of other rats.  Brain inflammatory and fat changes seen in the rats were similar to those found in people with autism. But perhaps most interesting to MacFabe was that the behaviours appeared reversible — dangling the prospect autism can be treated.  “The interesting thing is the behaviour comes and goes as the (rat) broke down the compound,” he said.

In other studies, proprionic acid when injected into test animals, propropionic acid depletes the brain of the calming neurotransmitters, GABA, serotonin, and dompamine.  It also impairs impairs the formation of lipids such as phosphatidylethanolamine, phosphatidylserine and phosphatidylecholine that insulate (mylinate) neurons and enable them to transmit signals efficiently. 

Proprionic acid may also skew metabolic pathways in the brain, converting excessive amounts of glutamine and glutamic acid and asparagine to glutamate and aspartate, which act as excitatory neurotransmitters.  Many individuals within the autism spectrum have elevated levels of glutamates and aspartate.  So proprionic acid may lead to the brain produce elevated levels of excitatory neurotransmitters, leading to over-excitement of neurons and damage to the brain from MAO trying to break down these neurotransmitters as they leak from neuron vesicles and resultingin the production of neurotoxic metabolites.  This also explains why it is so important for kids on the spectrum not to eat high processed foods that often include excitotoxins such as MSG (monosodium glutamate) and diet pop containing Aspartame.

MacFabe, Frye and Melynk screened about 215 autistic kids at a major U.S. clinic and found 17% had bio-chemical changes — a unique pattern of a compound known as acyl-carnitine — virtually identical to the rats that displayed autistic-like behaviour and brain changes.The team’s research also mentions some patients with autism have low levels of a compound called carnitine, which is important in metabolizing fatty acids.  The brain is primarily made up of fats.

Ammonia is also produced by overgrowths of pathogenic bacteria.  Ammonia is also absorbed into the bloodstream and easily crosses the blood-brain barrier.  Ammonia also impacts neurological development; it binds to and over-excites the NMDA receptors of neurons, generating a "wired" or high  anxiety state.  This anxiety can impact the body's adrenal system, causing the body to be a perpetual state of  fight or flight. When this occurs, the body produces excessive amounts of cortisol, which interfere with learning when present on a chronic basis.  Activating the flight or fight mechanism also causes the body to dump magneisum and zinc in to muscle tissues to prepare for rapid movement - once they are used in the muscles, these minerals are excreted from the body. This results in individuals within the autism spectrum being chronically low in magnesium and zinc. 

Ammonia and proprionic acid are but two-by products of intestinal overgrowth that impact metabolic processes and brain function.

Key Neurotransmitters


Serotonin is a key brain chemical that is been identified in the physiological abnormalities in ASD and AD/HD.  Serotonin is made from tryptophan with the help of vitamin C, folate, iron, calcium and vitamin B6.  Tryptophan is an amino acid, which is a building block of protein.  Children with developmental disorders often show amino acid deficiency including tryptophan.  They also have an inability to effectively convert B6 to it’s active form P5P.

Serotonin is responsible for regulating:

  • Learning
  • Memory
  • Sensory Perception
  • Noise sensitivity
  • Mood
  • Behaviour
  • Sleep
  • Appetite
Insufficiency of serotonin can contribute to symptoms of:
  • Depression
  • Appetite Cravings
  • Brain Fog
  • Low IQ
  • Anxiety
  • Panic Attacks
  • Insomnia
  • Eating disorders
  • Migraines
  • Ease of distraction or ADD

In autism, there can be too much or too little serotonin.  Often serotonin uptake inhibitors seem to reduce OCD behaviors and anxiety while there are conversely elevated levels of serotonin in whole blood cells and platelets.  A recent study showed that autistic children have a reduction in serotonin transporter binding in the medial frontal cortex, midbrain, and temporal lobe areas. 

Many individuals on the autism spectrum use Melatonin to help promote sleep. This then converts to serotonin during the day.  One has to be careful about using neurotransmitters directly (as opposed to their precursors) because the brain employs a feedback loop in regulating neurotransmitters.  If you supplement with a neurotransmitter and brain determines there is enough of it, it will stop making its own natural supply.  That's why sometimes people find initial benefit when supplementing with a neurotransmitter such as Melatonin and it gradually becomes less effective.  I recommend using a neurotransmitters as supplements every around 3 times a week, spacing it out, to prevent the feedback loop from activating.


Dopamine is needed for fundamental brain function.  Dopamine receptors have abnormal form in children with AD/HD.  The methylation cycle provides the primary fuel for dopamine receptors in the brain.  Children with autism and ADHD often have dysregulation in their dopamine system.  Low dopamine levels impair attention and focus.  High dopamine levels cause the mind to race and increase sensory perception which causes an overload on the brain’s ability to process.  Dopamine is produced from the amino acid tyrosine with the help of iron, vitamin C, folate, vitamin B6 and tetrahydrobiopterin.

A recent study indicates that musicians and individuals within the autism spectrum have increased dopamine DRD4 receptor mRNA expression.

Dopamine is responsible for regulating:

  • Sensitivity and processing of information
  • Perception of change
  • Relaying information
  • Fundamental brain function – cognition
  • Motivation
  • Emotional Responses
  • Attention and Focus
  • Movement
  • Posture

A deficiecy of dopamine is also found in individuals with Parkinson's disease.

GABA and Glycine - The Primary Calming Neurotransmitters

The brain's primary calming neurotransmitters are GABA and glycine.

GABA (gamma-aminobutyric acid) is a calming neurotransmitter that inhibits neurons from firing.  It is created from glutamate with the help of B6, zinc and taurine.  Research into the autistic brain has identified an imbalance in glutamate to GABA receptors.   Deficient levels of GABA or problems with GABA receptors are thought to play a role in the excitatory elements of autism and ADHD. 

Vitamin B6 is critical to the manufacture of GABA; it is frequently deficient in individuals within the autism spectrum.  The most bioavailable form of B6 is P5P. 

Identifying and addressing problems with neurotransmitter systems is a key component to biomedical treatment of Autism Spectrum Disorder and ADHD as well as many other developmental disorders.

Glycine, an amino acid, also functions as a calming neurotransmitter.  Several forms of glycine, including pure glycine, dimethylglycine, and trimethylglycine have been found to be of benefit for individuals with autism.


Acetylcholine very widely distributed excitatory neurotransmitter that triggers muscle contraction and stimulates the excretion of certain hormones. In the central nervous system, it is involved in wakefulness, attentiveness, anger, aggression, sexuality, and thirst, among other things. It also plays a critical role in encoding of new memories.  It can act as an inhibitory or excitatory neurotransmitter.

Alzheimer's disease is associated with a lack of acetylcholine in certain regions in the brain. Acetyl Choline also promotes REM (Rapid Eye Movement) Sleep state that is associated with dreaming. 

Citicholine and CDP choline and choline bitartrate have been found to be beneficial in helping some individuals within the autism spectrum.

Other Neurotransmitters

To be considered a neurotransmitter, a molecule must meet several criteria:

  1. It must be produced inside a neuron, found in the neuron’s terminal button, and released into the synaptic gap upon the arrival of an action potential.
  2. It must produce an effect on the postsynaptic neuron.
  3. After it has transmitted its signal to this neuron, it must be deactivated rapidly.
  4. It must have the same effect on the postsynaptic neuron when applied experimentally as it does when secreted by a presynaptic neuron.


Over 60 different molecules are currently known to meet these criteria:

Among the small molecules constituting the “classical” neurotransmitters, the best known are:

  • acetylcholine
  • serotonin
  • catecholamines, including epinephrine, norepinephrine, and dopamine
  • excitatory amino acids such as aspartate and glutamate (half of the synapses in the central nervous system are glutamatergic)
  • inhibitory amino acids such as glycine and gamma-aminobutyric acid (GABA; one-quarter to one-third of the synapses in the central nervous system are GABAergic)
  • histamine
  • adenosine
  • adenosine triphosphate (ATP)

Peptides form another large family of neurotransmitters, with over 50 known members. Here is a very partial list:

  • substance P, beta endorphin, enkephalin, somatostatin, vasopressin, prolactin, angiotensin II, oxytocin, gastrin, cholecystokinin, thyrotropin, neuropeptide Y, insulin, glucagon, calcitonin, neurotensin, bradykinin.

Certain soluble gases also act as neurotransmitters. The most important member of this category is nitrogen monoxide (NO).

In general, it is a very bad idea to have an autistic child receive "laughing gas" (NO) as an anesthetic for dental procedures.

These neurotransmitters act by their own distinctive mechanism: they exit the transmitting neuron’s cell membrane by simple diffusion and penetrate the receiving neuron’s membrane in the same way.