A Second Serving of Neurotransmitters, Please!

This is the fourth article in a series on brain function and health, a topic relevant to many with autoimmunity. For the introductory post to the series, click here. The second article is about brain structure and function. Click here for the third article, about neurons and synapses.

So far in this series, we’ve learned the basics on brain structure and function, the job of neurons in the brain, and that neurotransmitters are tiny molecules critical to the quadrillions of interactions that happen between neurons and other cells every moment we are alive. In this article, we’ll look more deeply at the main brain neurotransmitters, and what roles they play in our mood, health, and daily function. This knowledge is valuable for gaining a sense of how our brain function can be affected by autoimmunity, aging, and other sources of brain degeneration.

What Are the Main Neurotransmitters?

There are two general types of neurotransmitters: inhibitory and excitatory. Excitatory neurotransmitters stimulate their target neuron, encouraging whatever neurologic pathway it interacts with. Inhibitory neurotransmitters calm their target neuron, calming the neurologic pathway associated with it. Let’s take a look at the main neurotransmitters’ typical functions, as well as signs and symptoms that levels are too high or too low.

Inhibitory Neurotransmitters

GABA (Gamma-aminobutyric acid)
Often referred to as “nature’s Valium,” GABA is sent out to balance over-firing of excitatory neurotransmitters. It regulates norepinephrine, adrenaline, dopamine, and serotonin, and is a significant mood modulator. It helps control muscle activity and is important in the visual system.

Low GABA can lead to insomnia, mood disorders, and anxiety. Drugs that increase GABA levels in the brain are used to treat epileptic seizures and tremors in patients with Huntington’s Disease, as well as quell anxiety.

Excitatory Neurotransmitters

DOPAMINE
Dopamine (DA) is considered to be both excitatory and inhibitory. A member of the neurotransmitter family called catecholamines, it is the precursor for the neurotransmitter norepinephrine. It is the “pleasure and reward” neurotransmitter. It helps with mood, gives us focus, and is involved in the control of complex movements. It is responsible for drive, motivation and desire to get things done. Dopamine is produced in large amounts when you fall in love or engage in addictive behavior such as smoking, using recreational drugs or gambling (remember, it’s the pleasure/reward neurotransmitter). Dopamine also plays an important role in schizophrenia and other neuropsychiatric disorders.

Low dopamine can lead to trouble with memory (where did I put my keys?), difficulty initiating or completing tasks, poor concentration, low energy, and lack of motivation. Using caffeine to improve these factors will push dopa into the synapse, but the downside is that it will eventually deplete the body of dopamine, making matters worse. A decreased brain dopamine concentration is a contributing factor in Parkinson’s disease.

Elevated dopamine has been observed in patients with poor gastrointestinal function, autism, mood swings, psychosis, and children with attention disorders.

SEROTONIN
Technically, serotonin (SE) is an excitatory neurotransmitter, yet many call it inhibitory because of its generally calming, mood-stabilizing effect. It is synthesized from the amino acid tryptophan. It regulates many processes such as carbohydrate cravings, sleep cycle, pain perception, body temperature, blood pressure, hormonal activity and digestion.

Low levels are associated with decreased immune system function. A lack of serotonin has been linked to depression and related neuropsychiatric disorders. Excess consumption of caffeine on an ongoing basis can cause a depletion in serotonin.

Most of our serotonin is actually produced in the digestive tract, which speaks to the importance of maintaining gut health, an issue common to those with autoimmune disorders.

GLUTAMATE
Glutamate (GLU) is the most widely distributed excitatory neurotransmitter in the brain and nervous system. GLU plays an important role in learning and memory.

Low levels can lead to tiredness and poor brain activity. Levels that are too high can lead to death of neurons in the brain, as well as contribute to depression, OCD (obsessive-compulsive disorder) and autism.

NOREPINEPHRINE (noradrenaline)
Norepinephrine (NE) is both a hormone and an excitatory neurotransmitter. Made from dopamine, it is responsible for stimulatory processes in the body. NE helps make epinephrine (adrenaline). It has been linked to mood, arousal, vigilance, memory, and stress. Newer research has focused on its role in both post-traumatic stress disorder (PTSD) and Parkinson’s disease.

Low levels are associated with lack of energy, decreased focus and sleep cycle problems. At high levels, norepinephrine can cause anxiety, stress, high blood pressure and hyperactivity.

EPINEPHRINE (adrenaline)
Essential to metabolism, epinephrine (EPI) helps to regulate attention, mental focus, heart rate, blood pressure, arousal and cognition. It inhibits insulin and raises fatty acids in the blood.

Low levels can result in fatigue and lack of focus. High levels are associated with ADHD symptoms, sleep problems and anxiety. Long term stress or insomnia can cause epinephrine to be depleted. If these factors remind you of adrenal fatigue, you are right on track! Made from norepinephrine, it is released from the adrenal glands.

ACETYLCHOLINE
Acetylcholine (ACH) is our learning and memory neurotransmitter. It governs muscle contractions, and causes glands to secrete hormones. Damage to the pathways that transmit acetylcholine is associated with Alzheimer’s Disease. Outside the brain, acetylcholine is the main neurotransmitter in the parasympathetic nervous system – the part of our nervous system that controls functions such as heart rate, digestion, secretion of saliva and bladder function.

Low acetylcholine can be associated with poor focus and memory, slow or confused thinking, difficulty finding words and introversion. High acetylcholine may be related to depression, anhedonia, mental fatigue, and digestive complaints.

Excitation and Inhibition: The Juicy Stuff!

As you can see above, neurotransmitters are critical for most of our bodily functions, from digestion to cognitive function to mood. Even though they are sorted into two categories, the designation of excitatory or inhibitory doesn’t always mean that’s the outward effect a neurotransmitter (NT) will have on the body. The categories refer more to the effect a NT will have on the neural pathway it is interacting with.

Consider that the common expectation that amino acids used for neurotransmitter support will always cause a certain response, such as GABA causing relaxation, or tyrosine being energizing. They do work that way for some people, but not for all. If dopamine (an excitatory neurotransmitter) excites an inhibitory neuron pathway, the result is inhibition because it is exciting the inhibitory response. If GABA (an inhibitory neurotransmitter) stimulates an inhibitory pathway, it inhibits inhibition, creating an excitatory response. For example, some people take GABA to help with anxiety. Many do experience a relaxing effect from it, but some instead find they become more agitated; it depends on what neural pathways were involved in the process.

The point is, pay attention to how you respond to neurotransmitter support; your body will be honest with you. In three separate experiments to determine my reaction to GABA supplementation, I experienced a different result each time – relaxation, agitation, and no result. But that leads me down the leaky blood-brain-barrier wormhole, so let’s stay on track. More on that in a later post, promise!

Origins: Neurotransmitter Precursors

I love charts and diagrams! I find them very helpful for understanding relationships between things. Below is a chart that shows the precursors, or building blocks, for the above neurotransmitters (NT). Neurotransmitter production happens in complex production pathways, with some NTs leading to the production of others. This production demands the right amount of certain nutrients in the diet, mainly in the form of amino acids (proteins). We’ll go into more depth on the topic of diet for proper NT production in a future post. On the chart below, the NTs mentioned on this page are highlighted in blue.

Now we have the basics on brain structure and function, the job of neurons and neurotransmitters, and clues to how they might be related to some of the common symptoms many of us with autoimmunity deal with on a daily basis. In the rest of this series on the brain, we’ll explore more specifically how the neurotransmitters relate to mood and the dreaded “brain fog,” and ways to work toward restoring and maintaining brain health and mental/emotional balance. I look forward to sharing it with you; it has been fundamental to my healing journey, and I am grateful to have access to the information.