Got Anxiety and Depression? Part 2

It’s Not Just About Your Crappy Life

To be clear, I do not believe ALL causes of mood disorders are PURELY physiologic. There are MANY life circumstances and experiences that are major contributors to anxiety and depression. I do not dismiss these experiences as “inadequate” or “minor players” in creating anxiety or depressive illness.

What I AM saying is that life stressors ALONE may not necessarily be ENOUGH to create symptoms. I’m saying it’s worth LOOKING at other reasons that your brain biochemistry is off. And I will CONTINUE to use ALL CAPS throughout this post for EMPHASIS. (…terrific. —Ed.)

Anxiety, depression, OCD, panic disorder, bipolar disease, schizophrenia, ADHD, eating disorders and autism spectrum disorder are brain disorders. They are manifestations of brain inflammation and neurochemical imbalance. So is binge watching the Housewives of Atlanta. But to my point, our physiology plays a major role in creating these psychiatric symptoms. As clinicians we are obligated to try to uncover the “WHY” behind the symptoms.

THE ZEBRA approach to uncovering causes of Anxiety and Depression
The Why behind your symptoms

Dr. James Greenblatt, a prominent integrative psychiatrist uses “the ZEBRA” approach to figuring out what may lead to anxiety and depression. Now you may think this involves exotic petting zoos of sorts, or the donning of attire that is purely black or white or striped. Like the Hamburglar of yesteryear. (OK Boomer. —Ed.) But alas…to my chagrin, it does not.

The idea here is that every patient is unique. You can’t just slap on the drug cocktail du jour and think that’s going to be great for every patient who walks in the door. Think about how preposterous that is…
That’s like saying “Well Mrs. Jones, since most people fit into a size 7 shoe, even though you have size 9 feet, here are your size 7 shoes.” WHAT???? Aside from telling your doctor what to do with that size 7 shoe, the obvious response is that such a limited pigeon holed approach will not work for everyone.

Here’s a list of what needs to be addressed using “THE ZEBRA”

  • TAKE care of yourself – Fix your Sleep, Fix your Diet, Fix your Stressors
  • HORMONES – Balance your thyroid, adrenal, sex hormones, insulin
  • EXCLUDE reactive foods
  • ZINC and other minerals
  • ESSENTIAL fatty acids
  • EXERCISE and energy
  • B VITAMINS and other vitamins
  • RESTORE the Microbiome
  • AMINO acids and Protein

We will be focusing on what comprehensive testing looks like for someone who presents with Anxiety and Depression.

If You Don’t Test, How Do You Know You Have A Problem?

The short answer is, you don’t. Many things could be out of whack. Buckle up my friends. This one’s a doozy…

Check your hormones — this means looking at a complete thyroid panel (not just the typical TSH and T4 you get on routine blood work), a well timed female hormone panel if you are still menstruating, a metabolic profile that checks for breakdown products of estrogen, progesterone and testosterone, and finally a 24 hour adrenal panel that checks your circadian rhythm, total and free levels of cortisol. These hormones must be operating well to manage brain imbalances.


  • Blood testing for thyroid (TSH, total T3 and T4, free T3 and T4, antibodies to the thyroid like anti-TPO and Anti-Thyroglobulin and reverse T3.)
  • Blood testing for estrogen, progesterone, testosterone total and free and DHEAS
  • DUTCH urine testing for adrenal and female hormone metabolites
  • DUTCH cycle map testing for an in depth look at your hormone fluctuations throughout your menstrual cycle. Blood work is limited by measuring a single day of your cycle. This is often not adequate to assess what your hormones are actually doing.

Magnesium — Ironically, this mineral you do NOT need to test as magnesium deficiency is very pervasive. Magnesium plays a critical role in regulating melatonin and GABA levels in the brain, both associated with anxiety and sleep. There aren’t very accurate ways of determining your body magnesium level since blood levels are so tightly regulated. Your body will take it from the bone to keep you stable. Studies show that patients with the highest intake of magnesium have lowest depression rates. And there are a million reasons for this. Read my previous post about this for more information.


  • specialized red blood cell measurements that aren’t readily available. Here you can just ASSUME you are not okay.

Recommended supplement support:

  • Magnesium (Glycinate) (PE) 200 to 400mg at night. Typically this helps with sleep and bowel movements, but in the unusual event that it keeps you up at night, take it during the day.

Vitamin B6 — Combining Magnesium with vitamin B6 improves the benefit for anxiety and depression. Some individuals with certain genetic susceptibilities require higher than normal levels of B6 for optimal cellular function. It’s a good idea to consider adding in a b complex support even if you blood B6 levels are normal. Even if they are HIGH, this may actually indicate a cellular deficiency. I recommend using a special urine test to determine your cellular B vitamin status since blood testing may be inadequate.


  • Organic Acid Test. The O.A.T. measures the breakdown products of metabolism excreted in the urine. A block in certain chemical pathways can lead to either high or low levels of organic acids. This tells us if one of these pathways is impaired. It can detect problems in energy production, neurotransmitter metabolism, fatty acid metabolism, detoxification and nutrient status, particularly B vitamins.

Recommended supplement support:

  • Methyl B Complex 1-2 capsules a day or depending on testing may need less or more.

Vitamin B3 or Niacin — Did you know that 25-50% of schizophrenia patients admitted to psychiatric wards in the 1900s suffered from B3 deficiency? Cereal based diets in the past contributed to this epidemic. Now processed foods may be fortified with B3 but subclinical deficiencies exist. One of the early signs of B3 deficiency is, you guessed it, anxiety. Some people have an innate biological need for higher amounts of B3.


Recommended supplement support:

Vitamin B12 — Is associated with anxiety and depression. And dementia. And pre-Parkinson’s. And chronic fatigue. And tremors. And weird touch sensations. The list goes on… The trick here is that serum lab ranges say “normal” if you are between 200 and 1200 pg/ml. Yet, studies show that patients with levels between 200-400 pg/ml may suffer neuropsychiatric illness and anemia. Also note that B12 deficiency may be related to poor absorption in the gut, so B12 shots may be advised.


  • Organic Acid Test and blood B12 levels with “optimal range” being above 600. Also test levels of homocysteine, a marker of B12 deficiency when >8.

Recommended supplement support:

Zinc — this mineral is a cofactor needed in various brain neurochemical pathways. Often associated with symptoms of anxiety, depression and eating disorders.


  • Blood levels should be at the upper end of the normal range or at least above 100.

Recommended supplement support:

  • 30-50mg of Zinc daily. Recheck levels in 3 months. Be careful not to deplete copper levels after 12 weeks of use.

Microbiome imbalances — Ever hear of the gut brain axis? Me neither. Just kidding!  This refers to the direct neuro-immuno-endocrine communication between the brain and the gut microorganisms and overall milieu of your intestinal tract. I hesitate to write the word milieu because I’m not 100% sure how to even spell it, much less say it. Plus it sounds pompous. However, it does refer to the overall environment in the gut that absolutely impacts the brain neurochemical output. Butterflies in your stomach when you are nervous? Episodes of diarrhea when you are stressed out? It’s a thing. Carvel ice cream sundae? Well, that’s just a given, but so worth it!!


  • OAT and Stool testing may be of value here. Unfortunately, the local lab poop test is worth squat, but using advanced DNA molecular testing provides a very nuanced view of gut function. I like the GI MAP test.

Recommended supplement support:

  • This really depends, but many trials show significant psychiatric benefit with the use of probiotics.

Vitamin D — Required for SEROTONIN synthesis. Low levels are associated with risk of depression.


  • Blood levels. Treat aggressively. Ideal is >60ng/ml

Recommended supplement support:

  • K-Force is a 5,000 IU vitamin D capsule with vitamin K2 that helps with calcium absorption. The dose you need should be guided by your personal blood levels, but a total of 10,000 IU a week can be safely taken by most people.

Amino Acids — these are the critical building blocks needed to make neurotransmitters.


Recommended supplement support:

Folate — Folate deficiency or errors related to poor metabolism can be very common due to several genetic variants that reduce your body’s ability to make bioavailable forms of folate. Adequate BIOAVAILABLE folate is needed for neurotransmitter production, DNA synthesis and detoxification. Individuals may have a genetic mutation known as the MTHFR mutation that impairs that ability to convert folate to activated forms of folate. This has been associated with mental health impairment.


  • MTHFR mutation. Serum folate levels may be misleading as they measure all forms of folate including FOLIC ACID, the synthetic version found in fortified processed foods. Folic ACID is actually problematic for those with MTHFR mutations as they can occupy folate receptors without having the biological action that should follow.

Recommended supplement support:

Brain inflammation — Tons of literature shows an association between body inflammation and brain disorders. Checking to see what your baseline body inflammation is critical. These tests do not necessarily tell you WHERE the inflammation is coming from. But it does establish a baseline from which to compare once you start doing things to lower inflammation.


  • hsCRP, ESR, omega 3 index, homocysteine, ANA

Recommended supplement support:

  • varies depending on cause of inflammation but if your omega 3 index is low then supplementing with a quality fish oil would be nice.

➔ Well — that’s a start. There is a lot to consider. I am notorious at the local blood drawing labs for the 30 vials of blood that I order on my functional medicine patients. You may be rendered unconscious but it SO WORTH IT!! (That is if you can take the embarrassment of waking up on the floor with the nurse fanning you with a clipboard. Speaking for a friend. —Ed.)

Test Don’t Guess

Ask your doctor for the following array of blood tests:

  • B12, B6, B3, folate, homocysteine, methylmalonic acid
  • MTHFR genetic testing or do a 23 and me!
  • Zinc, magnesium
  • Vitamin D
  • Omega 3 index
  • Hs CRP, ESR, ANA
Functional Medicine Blood Test New York
You're In The Normal Range. Wait. What?! Dr. Sadaty's Share The Health

Work with a functional medicine MD if possible to interpret your blood tests in their OPTIMAL range.

  • Just getting “into” the lab “normal” range is not good enough. Remember that according to the lab range you are “normal” if you are within 90% of all blood test results. Whether you are at the very bottom or the very top of the range, you are “normal.” This is like passing a test by getting a D minus. Is that ideal?  Is that how you want your health to be? A D minus? Nope. You do not.
  • Does this cartoon sound familiar? You present to your doctor with a variety of complaints and concerns about your health but the tests come out “normal range.” That’s kind of BS. And if your tests are actually OPTIMAL, which is not the same as squeaking into normal range, then you must dig deeper using more sophisticated testing and assessments. The Medical Medium is cool, but there must be something more to your treatment plan than celery juice…just saying.

Consider working with a functional medicine MD…

…to obtain and interpret more sophisticated testing like OAT, DUTCH and GI MAP. There is a pretty decent amount of training involved to adequately interpret these tests. You can’t just “wing it.” Make sure your providers are familiar with these tests and how to interpret them for you.

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For more information about my wellness programs and my practice, check out my website Hey Look!  You are already here…

Ready for the legal disclaimer? Information offered here is for educational purposes only and does not constitute medical advice. As with any health recommendations, please contact your doctor to be sure any changes you wish to consider are safe for you!