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The 5 Biotypes of Depression
As developed by William J. Walsh, PhD

Arkansas Nutrition and Natural Healing

Dr. Roger Trubey, Dr.PH, MPH, and Doctor of Integrative Medicine 362 Unger Trail, Mountain Home, Arkansas 72653

Call 501-538-4944

Mainstream medicine looks at clinical depression as a single entity rather than a collection of different disorders that must be treated differently.   They are essentially all treated with SSRI medications, drugs that are targeted toward the primary neurotransmitters dopamine, serotonin, epinephrine and norepinephrine.  The result of this approach, as we will see below, is that some will benefit, some will not and some will get worse.  A much better outcome would result if depressed and anxious patients would be given specific laboratory tests to determine their particular depressive biotype.

The biotypes by Dr. Walsh were developed with a database of 2,800 patients and over 300,000 chemical analyses of their blood and urine.  This huge database found that the depressed population had blood and urine chemistries that were significantly different from the general population which lead to the development of the 5 biotypes.

5 Types of Depression, how they are determined and how to improve

1. Undermethylated Depression (38 -40% of depressed individuals)

    a. Symptoms and traits of undermethylated depression
—Adverse reaction to folic acid High inner tension but calm demeanor
—Obsessive-compulsive tendencies History of perfectionism
—Self-motivated Seasonal inhalant allergies
—Good response to antihistamines High libido
—Low tolerance to pain High fluidity (tears, saliva etc.)
—Very strong-willed Competitiveness in sports
—High suicidal tendency addictiveness
—Sparse chest/leg/arm hair busy mind w/ negative self-talk
—Denial of depression frequent headaches
—Family history of high accomplishment noncompliance with therapies
—Rumination thoughts about past events oppositional defiance as child

b. Undermethylated depressed patients are low in serotonin, dopamine and norepinephrine
c. These individuals are often deficient in calcium, vitamin D and magnesium
d. Many also have a pyrrole disorder as well (this is biotype #4 below)
e. These individuals will not do well with folate, choline, copper, DMAE and pantothenic acid (B5)but will do well on supplements that improve methylation and supplements that enhance the neurotransmitters Tryptophan and dopamine
f. Individuals in this category come with two traits that tend to negate successful outcomes – denial of depression and non-compliance with any medical treatment
g. With tests for confirmation:

Whole blood Histamine level (will likely be elevated – above 70ng/ml)
A depressed SAMe/SAH ratio

2. Folate Deficiency Depression (about 20% of depressed individuals) these are overmethylated

a. Symptoms and Traits of Low Folate Depression

—Improvement after folate therapy High anxiety and panic tendency
—Adverse reactions to SSRIs hirsutism (males only)
—Food and chemical sensitivities low libido
—Dry eyes and mouth sleep disorder
—High artistic abilities and interest underachievement in school
—Nervous legs, pacing high pain threshold
—Noncompetitive in sports/games adverse reaction to SAMe, methionine
—Hyperactivity copper intolerance
—Upper body/head/neck pain Learning disabilities
—Estrogen intolerance
—Hallucinations – paranoid

The presence of 40% of the above symptoms is consistent with a folate biotype depression

  • b. These individuals report intolerance to SSRIs, antidepressants and antihistamines
  • c. Academic underachievement and incidence of ADHD is about 3 times higher than those in the undermethylated biotype
  • d. Individuals of this biotype should not use supplements of tryptophan, 5HTP, phenylalanine, tyrosine, copper and inositol – it will likely make them worse.  They generally have high levels of serotonin and dopamine.
  • e. Very likely that most of the school/movie theater shooters are in this group
  • f. If B12 is used it should be Hydroxyl or adenosyl B12 but not Methyl B12 (methylcobalamine)
  • g. With testing for confirmation:
  • Whole blood histamine (will generally be low – below 40ng/ml)
    Serum folate (will also be low)
    Methylation profile (an elevated SAMe/SAH ratio)

3. Copper Overload (hypercupremic) Depression (about 17% of depressed individuals)

      • a. Symptoms and Traits of Copper Overload Depression
—Severe anxiety, even panic Sleep disorder
—Hormone imbalances Hyperactivity in childhood
—Skin sensitivity to metals/rough fabrics ringing in the ears (tinnitus)
—Intolerance to estrogen/shellfish/chocolate inability to tan
—Severe worsening of depression after hormone therapy
—Intolerant of birth control pills or hormone replacement therapy


      • b. 96% of individuals with this biotype are women with the first episode of depression occurring during a hormonal event – puberty, childbirth, menopause, etc.
      • c. Individuals with this biotype have elevated norepinephrine but a depressed dopamine. Norepinephrine elevations have been associated with anxiety, panic and sleep problems
      • d. Elevated serum copper is commonly found in women with a history of postpartum depression.  They seem to have a genetic or acquired inability to eliminate excess copper after a pregnancy
      • e. Plasma zinc levels are generally low in individuals with this biotype
      • f. Tests for confirmation generally show an elevated serum copper level, depressed plasma zin
      • 4. Pyroluric Depression (about 15% of depressed individuals)
      • a. Symptoms and Traits of Pyroluric Depression
—Severe mood swings Inability to cope with stress
—Rages Absence of dream recall
—Inability to tan – sunlight sensitivity Morning nausea
—Sensitivity to bright lights & loud noises Slender wrists, ankles & neck
—Great midsection fat and upper thighs Delayed puberty
—Disturbed menstrual periods/amenorrhea Social anxiety –stiff personality
—Bipolar individuals Lots of fears
—Obsessions with disasters Internal tension – tense feeling
—Poor short-term memory Pale complexion
—Antisocial personality disorder (sociopath) but no criminal tendencies
      • b. Most pyrolurics experience about 50% of the above symptoms and traits
      • c. Pyroluria is a genetically determined chemical imbalance involving an abnormality in hemoglobin synthesis resulting in a severe deficiency of zinc and vitamin B6
      • d. Onset of depression in this group is often triggered by a severe emotional or physical trauma.  Stress of all types increases the levels of pyrroles in the individual
      • e. This biotype tends to respond more quickly to nutrient therapy than other biotypes
      • f. Individuals of this biotypes cannot tolerate nutrients (or food) until lunchtime
      • g. These individuals are low in serotonin, Dopamine and GABA

5. Toxic Overload Depression (about 5% of depressed individuals)

      • a. Symptoms and Traits of Toxic Overload Depression
—Abdominal pain and cramping Increased irritability, even anger
—Headaches and muscle weakness Low energy
—Failure to respond to counseling or pharmaceutical drugs
—Depression that arises suddenly during a period of relative calm and wellness
      • b. This biotype is generally looked for when the other biotypes have been ruled out and there is no casein/gluten sensitivity or thyroid imbalance.
      • c. A provocation test for heavy metals will almost always reveal elevated levels on nearly everyone.  But in this group the toxic metals are also causing depression
      • d. The most common metal toxins are mercury, lead, cadmium and arsenic
      • e. Other toxins can also cause depression including mold/fungal toxins, chemical toxins, toxic effects of viruses and bacteria and food toxins or food intolerances

Tests to Evaluate the 5 Biotypes

        • 1. Methylation Profile (plasma)
          • 2. Serum folate
        • 3. Metabolic panel (Kryptopyrrole, serum copper, zinc plasma & Whole blood Histamine
        • 4. EDTA/DMSA provocation of heavy metals (if all the above are negative)
        • 5.Check ability for three step heel-to-toe walk


Please take note: you cannot determine methylation status, copper excess or zinc deficiency or some of the other biochemical abnormalities without proper testing.   Self diagnosis and supplementation without proper testing is never recommended .  Too many people will get their biotype completely wrong, and will likely make things far worse for themselves.