Biological Causes of Anxiety Part 2


Read Part 1 of this series, which digs deeply into nutrient deficiencies.

Here I present a model of biological root causes of anxiety and depression, designed by integrative psychiatrist Dr. James Greenblatt, called THE ZEEBRA. If you have anxiety or depression, it’s worth it to check each component in this model. One or more of these could actually BE the root cause or they could be co-contributors. In either case, cleaning up these biological factors may significantly help your recovery.

Psychiatrists have assumed, without proof, that depression results from chemical imbalances in the brain. Treatment has primarily consisted of prescribing medications that may restore proper balance. But even if we had medications that could do so consistently, shouldn’t we be looking for the causes of the imbalance?” ~Greenblatt

T is for Take care of yourself.
H is for Hormones and Herbs.
E is for Exclude.
Z is for Zinc (and other minerals like magnesium).
E is for Essential fatty acids and cholesterol.
E is for Exercise and energy.
B is for B (and other) vitamins.
R is for Restore.
A is for Amino acids and proteins.

The previous post delved into Z and B (minerals and vitamins), which is one place to start within this model. Here we dig into the rest of the ZEEBRA model, starting with the lifestyle components: T (take care of yourself), the third E (exercise and energy), and A (amino acids and proteins). These are things you can do on your own. Then we will visit H (hormones and herbs), E (exclude), and R (restore).

T is for Take care of yourself.

This means get your sleep, stress management, and food in order. This is called “lifestyle medicine” in the functional health sphere. These are clearly big topics, so let’s zero in on specifically what the research tells us in these three areas.

1. Sleep

This is tricky as sleep problems (from insomnia to oversleeping) are a symptom of anxiety and depression. However, research shows that sleep problems can create anxiety and depression and that it’s important to:

  1. Get checked for sleep apnea, which doesn’t only occur if you’re male or overweight! Women and lean people also have apnea and this is a serious condition of which mental health concerns are only one consequence. Read more about women and sleep apnea.
  2. Get a minimum of 8 hours of quality sleep per night. If this isn’t happening, make it a priority. I know, easier said than done! It’s up to you to make the time and space for quality sleep, and set up good sleep hygiene. You can try melatonin, sleep apps or programs like Rest Assured, or wearables like the Oura ring to improve your sleep.
  3. If you have insomnia, get a workup to find the root cause. It may be high cortisol, hidden stimulants, or hormone imbalances, among other causes.

2. Stress management

It’s probably no surprise that stress is shown to increase anxiety and depression. I think we can all agree that uncontrolled stress has a negative effect on our mental health! One biological way that stress does this is by increasing inflammation. Unmanaged stress actually creates inflammatory biochemistry in your body and your brain. Anxiety and depression thrive in an inflamed brain.

Stress is a normal part of life, but sustained stress is damaging to our bodies. Besides reducing the stressors in your life that are in your control, the biggest intervention here is to work with the ways that you experience and react to stress. You can learn how to stay even-keel amongst all types of stress. Mindfulness meditation, breathwork, and mindful movement practices like yoga or chi gong are great tools to change how you experience and respond to stress.

Unwind stress on a daily basis so that it doesn’t accumulate. This may be talking mindfulness moments, exercising, dancing, playing, talking, journaling – find what works for you and choose to make the time every single day.

3. Food

This is a big topic, but if we zero in on what the research tells us, it’s largely about sugar, protein, and inflammation.

  1. Sugar intake affects moods, emotions and mental health. This is because it drives your blood sugar up… and then down. Low blood sugar, high blood sugar, and wildly fluctuating blood sugar are shown to contribute to mood swings, anxiety and depression. The simple solution is to reduce sugar and refined carbohydrate intake. If this feels like a hard project, get help from a coach or nutritionist, or do my Functional Whole30 program which is a 30-day break up with sugar.
  2. Protein is essential to make amino acids to build your neurotransmitters (this covers another letter in the model, which is A for amino acids from protein). You can’t make serotonin or dopamine without amino acids. If you’re vegan or if you don’t eat 65 or more grams of protein per day (3 palm-size portions), then you can take free form amino acids, and even gear these towards the neurotransmitters you’re trying to build (with guidance).
  3. Inflammation in the body will also cause inflammation in your brain. Anxiety and depression exist in inflammed brains. Root out inflammatory foods from your diet. This means highly processed food, junk food, fast food, and processed oils (vegetable oil, corn oil, trans-fats). Boost anti-inflammatory fats like olive, avocado, flax, borage, fresh nuts and seeds, and omega3-rich seafood. Eat lots of fresh vegetables and fruits, 5-10 servings per day (1 cup is a serving). Research shows that diets rich in fiber and phytonutrients from fruits and vegetables decrease inflammation and depression. Lastly, on an individual basis, identify foods you are “sensitive” to. Learn more about how to identify food senstitivites.

E is for Exercise and energy


Exercise improves mental health – this is shown in the research. It’s not hard to convince people of this, yet it can be hard to get some people to actually DO it. Here are the three top reasons for this:

“I don’t have the time.” Choose to make the time. Put it in your calendar as non-negotiable.

“I don’t like to exercise.” Find one or more ways of moving your body that you do like. Dance. Rollerblade. Bike. Swim. Hike. Find something you enjoy doing or you won’t want to do it.

“It’s too hard to exercise.” If this is because of a physical limitation, get help from a PT or trainer. There’s almost always SOMETHING you can do. If it’s a problem with energy…..


This refers to your experience of energy production. Do you feel like you don’t have the mojo needed to move your body and then recover from it? You make energy from food and nutrients, inside your mitochondria, and thyroid hormone is required. You also need adequate sleep and oxygen. These are areas to explore with your healthcare team.

H is for hormones and herbs

These are lumped together because they both start with H. Greenblatt is referring to evidence that sex hormone deficiencies and imbalances can contribute to anxiety and depression. If you suspect this is you, get your hormones tested! The herbs he refers to are those that reduce inflammation (remember the brain is inflamed when there’s anxiety or depression), as well as those that affect neurotransmitters and mood. The H category is one to get help with!

E for exclude and R for restore

Exclude means rooting out sources of inflammation, which is often in the gut, as 80% of your immune cells are located in your digestive tract. This can also include deeper inflammatory triggers such as visceral fat, viral infections, and toxins like metals or molds.

Restore refers to the gut microbiome. There is a ton of research on the effects of gut microbes on the brain.

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