Experiencing occasional anxiety is a normal part of life. However, people with anxiety disorders frequently have intense, excessive and persistent worry and fear about everyday situations. Often, anxiety disorders involve repeated episodes of sudden feelings of intense anxiety and fear or terror that reach a peak within minutes (panic attacks).

These feelings of anxiety and panic can interfere with daily activities, are difficult to control, are out of proportion to the actual danger and can last a long time. You may avoid places or situations to prevent these feelings. Symptoms may start during childhood or the teen years and continue into adulthood.

Examples of anxiety disorders include generalized anxiety disorder, social anxiety disorder (social phobia), specific phobias and separation anxiety disorder. You can have more than one anxiety disorder. Sometimes anxiety results from a medical condition that needs treatment.

It is the general medical consensus that anxiety is a combination of imbalanced chemicals in your brain (neurotransmitter), often paired with the occurrence of a traumatising life-event. Common treatment involves cognitive therapy and drugs that influence these brain neurotransmitters. How can Functional Medicine help? As always, it aims to find the underlying root cause for the biochemical imbalances.

But what happens in the brain when we experience anxiety, or even a panic attack?

If our brains’ chemicals such as hormones and neurotransmitters are balanced, we are happy, relaxed and can make conscious decisions on how to react (emotional intelligence). Ideally, our prefrontal cortex, where we make decisions, is turned on and overlooks our ‘primal’ emotions that come from the back of the brain. When a perceived threat shows up, a well functioning prefrontal cortex can evaluate the impact, consider the pro’s and con’s of different reactions, and come up with a solution that serves us best in the short- and also long-term. It can judge and has foresight.

However, if the brain chemicals become derailed, this feedback loop doesn’t work as well anymore. The back of our brain, our ancestral emotional and fight-and-flight center takes over, and the prefrontal cortex (the conscious mind) gets shut down. We find ourselves overreacting, ruminating (overthinking negative possibilities), snapping at friends and loved ones, and not able to clearly think and react in the best possible way. You may find yourself ‘over-reacting’ where you would have preferred to stay calm, or crippled by fearful thoughts about the future. You may start to resent yourself for not being able to ‘be yourself’. You may not be able to sleep due to racing thoughts, becoming overwhelmed with work and life tasks that used to excite and positively challenge you. You may be unable to concentrate, not able to get out of bed in the morning, or simply feeling exhausted. You may even be diagnosed with anxiety, depression or burnout. You may self-medicate with drugs.

Which part of the brain we turn on relies heavily on something called neurotransmitter. Neurotransmitter are little signalling molecules in our brain and entire body. Some of the better known ones include serotonin, dopamine, glutamate and GABA. They largely control which signals get sent, and how we act and react.

Even if life circumstances might be difficult, reducing our amygdala’s response, strengthening the prefrontal cortex, and levelling out our neurotransmitter can help us deal with them more easily, finding solutions and allowing us to feel in control of our reactions and future.

Which neurotransmitters are involved, what derails them, and how can we influence this to become the best version of ourselves?

 Neurotransmitter & Their role in anxiety

We need just enough of the excitatory neurotransmitter dopamine, noradrenaline, and glutamine to be sharp and focused, but level them out with the adequate portion of their calming counterparts, mainly GABA and serotonin. Science generally believes that we have too much of the excitatory neurotransmitters and not enough of GABA and serotonin floating around our brains when anxiety hits.

Site note: Recent research is challenging the role of serotonin as a purely calming neurotransmitter, with new findings suggesting we do need enough of it, but if we have too much, it may in fact be contributing to anxiety in itself, especially social anxiety. More on this later.

So how do these neurotransmitter get made, and how do we break them down?

In a normally functioning brain, we constantly create neurotransmitters for signal transmission, and then break them down when we don’t need them anymore.

Neurotransmitter are made from protein. When we eat protein rich food, the body breaks it down and converts it into our neurotransmitter, with the help of enzymes, vitamins and minerals.

If we don’t have enough of the building blocks (protein), helper substances (vitamins and minerals) or enzymes to create or break down the right amount of neurotransmitter, we start ‘misfiring’ in the brain. Sometimes we have enough of the right nutrients, but molecules such as heavy metals, infections or inflammation are blocking the production or breakdown.

Genetic predispositions to anxiety

You may have noticed that certain character traits run in families.  In fact, we do need the help of our genes for the above described well-functioning production and breakdown of neurotransmitter. Our genes code for the enzymes that help these processes along, so if we have mutations (SNP’s) in any of them, we may be more prone to low or high levels of one or another.

However, as research is advancing, we learn more and more on how we can bypass certain genetic weaknesses and mutations by adding in more of specific nutrients, vitamins and minerals needed to speed up a genetically slowed process, and on the other hand, remove certain triggers that are genetically riskier. This is called epigenetics, and such an exciting and empowering new era of precision healthcare. Epigenetics shows that genes are only the load in a gun, but our lifestyle choices ‘pull the trigger’ (or not).

But lets look into the actual neurotransmitter involved in anxiety disorders, how they may become derailed, and how we can influence them.

Serotonin is an important neurotransmitter in the body. Low values have been correlated with depression and constipation.

Excessive levels have been correlated with social phobias.

Serotonin gets further converted into melatonin, our sleep hormone. So if we don’t have enough serotonin, we may have trouble producing enough melatonin at night to sleep.

Dopamine plays a major role in reward-motivated behaviour.

Dopamine in optimal ranges supports internal motivation and drive, a ‘go-get-it’ mentality.

For example, if we have the right amount of dopamine in the brain, we are motivated, feel good and happy, are driven and focused. If we don’t have enough of the neurotransmitter dopamine, we will find it difficult to self-motivate, become lethargic, and lack drive. We might try and compensate by eating, which raises dopamine, or take drugs. If we have too much dopamine however, we become ‘overstimulated’, anxious and have difficulty making good decisions, as our prefrontal cortex shuts down. Too much dopamine also makes us obsess about things or people. If we cycle between too much and too little dopamine, we may become ‘bipolar’ or ‘manic depressive’. It is a very intricate balance.

GABA is one of the main calming neurotransmitter. It makes us ‘zen’ and chilled out. It gets converted from glutamate, which is one of our main excitatory molecules in the brain.

Another important neurotransmitter that has been implicated in anxiety is noradrenaline, which has excitatory properties.

New science indicates that anxiety and its derailed neurotransmitter can have many different components to it.

Estrogen, histamine and their relation to anxiety

& anxiety related sleep trouble

Estrogen has been shown to be tightly correlated with histamine and serotonin. Science is not quite conclusive on the exact effect on serotonin as yet, but it appears that when we are in a state of ‘estrogen dominance’, which is defined by an overabundance of estrogen in relation to other hormones such as progesterone, we produce and release more histamine, which has excitatory effects, but also serotonin.

Excessive estrogen and histamine levels in the brain may be related to anxiety and the often associated inability to wind down at night, due to histamine’s role in the sleep-wake cycle.

Low estrogen levels, as often seen in menopause, may lead to too low levels of serotonin, and with it depressive thoughts.

You may have noticed your anxiety coming on after an afternoon of eating cheese and drinking wine, and related it to the alcohol alone. While alcohol does have effects on GABA (more on this later), and wine and cheese are also high in histamines. If you have a problem breaking down histamines (which can often be genetically predisposed), this may be one of the reasons your heart starts racing and the mind won’t calm down.

GABA and alcohol

Many experience anxiety after a night of drinking, or other substance abuse. Alcohol increases levels of the calming GABA short-term, which is why drinking that glass of wine at night can have such a soothing effect. However, if we go overboard, we deplete the body’s GABA levels, and drop too low the next day, leaving us anxious and the opposite of zen.

The earlier mentioned estrogen dominance can make this worse, as progesterone acts similar to GABA, and may perpetuate an already imbalanced neurotransmitter status.

Copper and anxiety

Copper overload can be another one of the factors in anxiety disorder. Copper increases the conversion of dopamine to noradrenaline, which can leave us wired and anxious.

Copper has been shown to increase estrogen levels, and as such further contribute on different levels.

Inflammation, food intolerances & GUT Problems

Inflammation derails your serotonin pathway from the happy, blissful and peaceful, to a ‘toxic’ pathway that creates depression and mood disturbances.

Often mentioned is nowadays that serotonin not only gets produced in the brain but also the gut. So healing the gut should naturally increase serotonin in the brain? Unfortunately preformed serotonin cannot cross the blood-brain-barrier, so the amount of serotonin in the gut does not directly influence the amount available in the brain. However, our gut plays a very big impact on many other levels. If our gut is compromised, we may allow larger food particles and bacterial particles into our blood (LPS), triggering our immune system, creating food intolerances. The activated immune system releases inflammatory molecules that can cross the blood-brain-barrier, and block the pathways to happy neurotransmitters.

Other influencing factors

• Nutrient deficiencies such as the precursors (protein) and cofactors (vitamins and minerals such as magnesium, B vitamins)
• Omega 3 deficiencies: omega 3 fatty acids help coat the brain cells, but also to lower inflammation
• Blood sugar imbalances (a reliance on sugar for energy and consecutive blood sugar drops)

Contributors to anxiety from a Functional Medicine perspective:

• Blood sugar swings
• Brain inflammation
• Gut imbalance such as ‘leaky gut’, infections and gut bacterial imbalances (SIBO, IBS, Candida, etc)
• Hormonal imbalances, especially estrogen dominance
• Excess exposure to heavy metals and other pollutants
• Deficiencies in nutrients that are important building blocks for your brain biochemistry, production and breakdown (protein, vitamins and minerals)
• Copper overload
• Histamine intolerance
• Lifestyle factors such as life-work balance, relationships, externalizing problems
• Unresolved traumas
• Excess alcohol and other substance abuse

So, what to do about it?

Find your underlying triggers and address them. Ideally with the help of a Functional Medicine practitioner that is trained in this field. He/she will be able to guide you to the correct testing, and assist you in creating a treatment protocol that fits your genes, test results and lifestyle.

You may still benefit from working through unresolved traumas and to rebuild new behavioural patterns. However, if your brain biochemistry is off charts, this may be an uphill battle. If you can remove triggers and add in the right building blocks, you may find yourself much better able to turn the prefrontal cortex back on and take control over your life.