Brain on Fire: Anxiety, Depression, Genomics and Inflammation

I work part time at a very unique pharmacy that also has a wellness department where customers can get education on and purchase professional quality nutritional supplements. One of the more common things I am asked is "what do you recommend for anxiety?" My answer is always "It depends". Feelings of anxiety (or depression, cravings, addictions, mental focus etc) have a multitude of possible causes. Picking the right supplement depends on figuring out what is actually out of balance. My focus for this post is anxiety and depression, but the same issues are often at play with food cravings, addictions, memory and focus.

What are Neurotransmitters?

Neurotransmitters are special chemicals used in the nervous system and brain to communicate between cells. Neurotransmitters can be stimulating or calming. There are 3 main groups of neurotransmitters: The catecholamines (dopamine, nor-epinepherine, and epinepherine), serotonin/ melatonin, and glutamate/ GABA. Each of these groups exists in its own "metabolic" pathway, meaning that the molecules in each group are closely related to each other. Here is an introduction to the main neurotransmitters:

  • The catecholamines are all stimulating in different ways.

  • Dopamine helps us focus and also helps us feel satisfaction, gratification.

  • Epinepherine is another word for Adrenaline - it is the main driver of the sympathetic nervous system. When in balance it helps keep us alert, when there is too much, we are in "fight or flight". Nor-epinehperine is the molecule between dopamine and epinepherine on their chemical pathway, and its actions are similarly a blend between the two.

  • Serotonin and melatonin are calming. Serotonin giving us a sense of calm and wellbeing.

  • Glutamate and GABA are very similar molecules but they have opposite actions.

  • Glutamate tells our brain to pay attention to everything (stimulating) and GABA tells our brain to ignore everything (calming).

Anxiety and depression are often assumed to be due to low serotonin (many Rx medications for anxiety and depression are focused on recycling serotonin). In truth, low serotonin is a factor for many people struggling to keep a calm, positive mood. But, as you can see below, there are many other things that can be factors in these common mood imbalances. The most immediate cause of many mood issues, is indeed neurotransmitter imbalance. However, there is almost always some REASON for the neurotransmitters to be out of balance. For most people, their mood challenges are a combination of the issues below, and so getting back into balance requires a multi faceted approach.

Feelings of anxiety can be caused by

  • Low serotonin (invasive, recycling negative thoughts)

  • Low GABA (monkey mind with no content, can't "turn off"

  • Too much dopamine (OCD like symptoms)

  • Excess glutamate (overwhelming sensory input - noise, color, light, conversations)

  • Excess cortisol (may feel like fight or flight)

  • Excess adrenaline / norepinepherine (may feel like fight or flight)

  • Too much or too little histamine (excess need for precision / perfectionism)

  • Low blood sugar (can feel spacy or fight /flight, headache, shaky, impending doom)

  • Inadequate or imbalanced nutrients (especially B vitamins and minerals)

  • Too much thyroid hormone (less common, - feels wired, but tired, fast heart beat)

  • Sudden drop in estrogen or progesterone (PMS, perimenopause)

  • Exposure to foods, chemicals or mold that cause inflammation in the nervous system

  • Genetics that make you more vulnerable

Feelings of depression can be caused by

  • Low serotonin (invasive, recycling negative thoughts)

  • Low dopamine (uninspired, unmotivated, unfocused)

  • Low norepinepherine (tired, unfocused)

  • Too much or too little histamine

  • Low thyroid (slow, cold, dry)

  • Low vitamin D (gloomy / cloudy, easy inflammation)

  • Excess progesterone (weepy, sad)

  • Imbalanced or poorly metabolized estrogen (more cranky / irritable)

  • Inadequate or imbalanced nutrients (especially B vitamins and minerals)


  • Genetics that make you more vulnerable

Inflammation: Brain on Fire

The phrase "Brain on Fire" is the title of a book by one of my medical heroes, Mary Ackerly MD. She is a psychiatrist in Arizona that realized that many of her patients were suffering from chronic infections, mold exposure, chemical exposures, old brain injuries, and food sensitivities. All of these things can cause subtle inflammation in the brain. When the brain is inflammed, it does not make or break down neurotransmitters in the same way as a healthy brain. Brain inflammation also affects the cellular metabolism and oxygen use of various parts of the brain. An inflammed or chronically hypoxic brain simply cannot function normally.

Many of my patients discover that the root of their insomnia, anxiety or depression is actually mold exposure, chemical exposures or food sensitivities. Resolving these issues often resolves the mood issues completely, or it facilitates the success of re-balancing neurotransmitters with specific nutrient protocols.


Getting your genome mapped is all the rage these days, especially with affordable services like 23andMe. Finding out what genes you have can be very helpful in customizing the support your body needs. It is important to remember that for most issues "genotype is not phenotype". What that means is that our genes are our potential for response to our environment, and that our environment determines what genes are turned on and off at any given time.

So while you may have genes that make it more difficult to keep your brain chemistry in balance, it is not set in stone that you will always be out of balance.

In working with MTHFr and mood genetics for the past 12 years, what I have found is that genomes tend to be self balancing if you look far enough. For example if a person has slow MTHFr and also makes serotonin slowly, they usually also have genes that mean they tend to break down serotonin slowly as well. This system works great if you have a perfect diet and no stress.

The same is true for inflammation. People have different levels of genetic sensitivity to things like gluten, heavy metals and mold. All of these can cause inflammation in then nervous system that has direct bearing on neurotransmitter balance and mood.

Combination treatments

Long term resolution of anxiety and depression usually requires a combination of approaches.

  1. Identify and remove foods that are causing inflammation. The most common are gluten and dairy. Unfortunately these foods are often the foods we crave as comfort foods. Why? Our body recognizes the food as inflammatory and releases endorphins (our natural opiates) to protect us from the pain caused by the inflammation. This literally gives us a little "high" from eating these foods, but still leaves us with the chronic inflammation.

  2. Identify and remove environmental causes of inflammation. Mold and other toxic chemicals wreak havoc on the nervous system, cause inflammation and sometimes directly interfere with brain function. Identifying these exposures is the first step in avoiding them! If these are present, you must eliminate the source of exposure before you will see any lasting improvement in mood or brain function.

  3. Identify vulnerable genetics and support with good nutrition and supplements. For some people this may mean taking the special methylated (activated) form of B12 and folate. For others it may mean avoiding folate and taking specific minerals or other B vitamins.

  4. Rule out endocrine issues. Getting your adrenal, thyroid and sex hormones tested may be helpful. Most hormone imbalances have multiple symptoms, beyond mood issues.

  5. Identify low neurotransmitters. These can be tested, but I find that the best results usually come from really focusing in on the way symptoms are manifesting for an individual . Each neurotransmitter has a particular "personality" that can help identify it. (see chart above)

  6. Customize supplements that reduce inflammation, help detoxify any chemical or mold exposures, and provide the nutrients to make and process neurotransmitters so that they can come back into balance.

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