This is a follow up to the blog I did last week about the 5 most common biochemical biotypes of depression. This week I’m going to share which lab tests you need to get done to figure out which depression biotype(s) are at the root of your symptoms.


Every so often a researcher comes along who makes your work as a clinician so much easier.

This is what Dr. Bill Walsh has done for all of us who practice integrative mental health. 

With his depression biotypes, we now have a 90 percent chance of identifying a major biochemical driver of a client’s depression with just a few simple lab tests.  

Finding Dr. Walsh’s research has changed how I work.

Where it used to be common for me to do half a dozen or more functional medicines tests (clients would asks, “What AREN’T you going to test for?”) now I usually do the few tests below and also get some general blood work, and I find that’s enough to start with.

This “small and focused” approach tends to work for me. It’s cost effective for clients and usually provides predictably good results.

The thing about an approach like this is that we can start by looking at a few key imbalances because we now understand what’s causing a majority of cases of depression.

Even though there are many possible causes of depressiona few just keep on coming up over and over again. And that’s where we start.

And after working with targeted testing, if things don’t go according to plan, then we dig deeper.

This is where a more full-functional-medicine testing approach comes in handy.

We can expand our search to other possible culprits like inflammation, yeast overgrowth or hormone dysregulation, among others.

The most important labs for depression

1) Whole Blood Histamine (WBH)– This is the simplest way to test for methylation status in the body.

Methylation is a very common, but essential biochemical process in the human body and brain essential to physical and mental health. In terms of mental health, your methylation status has everything to do with your personality.

Undermethylation is associated with chronic depression, obsessive compulsive tendencies, and addictions.

Overmethylation is associated with high anxiety, depression, sleep disorder, and hyperactivity.

Click here for a fuller list of under and over methylation  symptoms and traits. 

While many practitioners are currently doing genetic testing to identify gene mutations related to the functioning of the methylation cycle including MTHFR, Dr. Walsh still recognizes whole blood histamine as the most helpful marker to guide treatment for methylation issues related to depression and mental health.

In my experience, though genetic testing can be very interesting and helpful as part of an integrative clinical assessment (especially to look at what future emotional/behavioral propensities a person might develop under stress,) Whole Blood Histamine provides the most useful information needed to make clinical decisions about methylation status.

When more data is required, the Methylation Profile from Doctor’s Data provides a more comprehensive window into the specific real time issues with methylation. 

Ideal Walsh range for whole blood histamine:  40-70 ng/mL  

Treatment for undermethylation (WBH above 70, high histamine suggests low methylation)– Focuses on SAMe or Methionine with support of Calcium/Magnesium, Zinc, Vitamin C, Vitamin E

Treatment for Overmethylation (WBH below 40, low histamine suggests high methylation) Focuses on Folic acid and B12, with Vitamin C, B6, Zinc, Manganese, Vitamin E and Niacinamide  

2) Plasma Zinc– A number of recent articles have focused on zinc’s ability to decrease depression. An example of this trend in the academic literature is this article entitled “Zinc: the new antidepressant?”

Zinc’s effect is largely due to it role as a cofactor in serotonin production (and also to it’s role in promoting proper digestion of proteins, which is important for many with depression.)  

Thus, if you are deficient in zinc you will likely be deficient in serotonin. Low serotonin symptoms include depression, anxiety, agitation, and sleep issue. Click here for a more complete list of low serotonin symptoms. 

Ideal Wash Range for zinc: 90-135 ug/dL

Treatment for low zinc: Repletion with zinc to get to the level mentioned above.

3) Serum Copper– Copper is an essential mineral important for many of the body’s systems including communication between nerve cells, proper functioning of circulating blood vessels and formation of white blood cells. In the brain, copper is a cofactor for converting the neurotransmitter dopamine to norepinephrine.

When copper is within a tight range, all is good. But when copper levels rise in the body (mostly due to genetic reasons) it can lead to extreme anxiety resulting from copper’s propensity to lower dopamine and raise  norepinephrine. High copper is more typical in women than men, and often follows hormonal changes like puberty or postpartum.

Ideal Walsh range: 70-110  ug/dL

Treatment for high copper: Mostly focuses on Zinc supplementation as zinc draws down copper.

4) Kryptopyrrole (KP)- This is a test for the genetic condition known as Pyroluria. It’s is a home urine test that looks for levels of this byproduct of hemoglobin synthesis. At high levels, Kryptopyrroles latch onto zinc and B6 removing them from the body. High levels of KP also causes oxidative stress (leading to systemic and brain inflammation.)

As you probably guessed, the leaching of B6 and zinc causes mood problems because they are both are co-factors in making serotonin. Symptoms of KP include social anxiety, depression, stress intolerance and mood swings.

Ideal Walsh Range: 0-10 mcg/dL

Treatment of Pyroluria: Focuses on supplementing B6 and Zinc. People with Pyroluria are often intolerant of fish oil and need the omega 6 oil Gamma-Linolenic Acid (GLA,) in the form of Evening Primrose Oil or Borage Oil.

There are case reports of suicidal depression being significantly improved by stopping fish oil and starting GLA in a people with severe Pyroluria.

There is only one laboratory that I know of that does the assessment for KP accurately (the accuracy has to do with ways that the samples are handled before the are evaluated.) The lab to use is called Direct Health Access Laboratory

How to get yourself tested

I have found it best to work with someone trained by Dr. Walsh in his nutritional approach. Click here to access a database for Walsh trained doctors. These practitioners will be well-versed in the tests that will be most helpful for your unique situation and will have the expertise to create a corrective supplement protocol for your individual needs.

If you are not able to find a clinician in your area, I am trained in Dr. Walsh’s Advanced Nutrient Therapy approach and do phone consults anywhere. For more information go to my website.   

If you found this post useful, please pass it on to others that it might help. Also, if you want more articles like this sign up for my email list on my website.

In good (mental) health,

Dr. Josh

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