Here's an interesting site.
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After getting extensive biochemical data on more than 3,000 persons diagnosed with clinical depression, we found that 95% of them fit neatly into one of 5 separate biochemical classifications. Depression is not a single condition, but an umbrella term covering several completely different conditions. Anyway, we believe we have identified the 5 primary phenotypes..... each with their own classic symptoms and each with completely different treatment needs.
1) High Histamine (under-methylated)
40-70 is optimum histamine range for mental health considerations. Histamine is an important neurotransmitter which affects human behavior. This syndrome often involves seasonal variations in depression, obsessive-compulsive behavior, inhalant allergies, and frequent headaches. In severe cases involving psychosis, the dominant symptom is usually delusional thinking rather than hallucinations. They tend to speak very little and may sit motionless for extended periods. They may appear outwardly calm, but suffer from extreme internal anxiety. Most OCD patients with both obsessive thoughts and compulsive actions are in this category. Associated with under-methylation, which results in low levels of important neurotransmitters such as serotonin, dopamine and norepinephrine. Treatment focuses on the use of antifolates such as calcium, methionine, SAMe, magnesium, zinc, TMG, omega-3 essential oils, B6, inositol, and A, C and E. The dose of inositol is 500 to 1000mg. Choline is anti-dopaminergic and often makes undermethylated patients worse. Also bad are DMAE, copper and folic acid. Three to six months of nutrient therapy are necessary to correct this chemical imbalance. Symptoms will return if treatment is stopped. Two good labs for whole blood histamine are LabCorp and Quest. Also use a special absolute basophil count as a methlyation marker. The count must be direct and not differential. Alcian blue dye is the preferred staining agent. Best lab for this test is Direct Healthcare Access in Glenview IL 847 299 2440
2) Low Histamine (over-methylated)
Low-histamine depressives are usually nervous, anxious individuals who are prone to paranoia and despair. No seasonal allergies, but many food allergies and chemical sensitivity. Low libido. Obsessions but not compulsions. Heavy body hair. Nervous legs. Grandiosity. Many have a history of hyperactivity, learning disabilities and underachievement. They are over-methylated which results in elevated dopamine and norepinephrine levels. Treatment focuses on B3, C, B12 and , with about 2-4 months required for correction of the imbalance.. Also DMAE, choline, manganese, zinc, omega-3 essential oils, C and E. They should avoid methionine, SAMe, inositol, TMG and DMG.
3) Pyroluria
A stress disorder characterized by pronounced mood swings, temper outbursts, anxious depression. Inability to eat breakfast, absence of dream recall and frequent infections. The biochemical signature of this disorder includes elevated urine kryptopyrroles, a double deficiency of zinc and B-6, and low levels of arachidonic acid. Devastated by stresses including physical injury, emotional trauma, illness, sleep deprivation. Sensitivity to light and loud noises, dry skin, abnormal fat distribution, rage episodes, histrionic behavior. They also have low levels of arachidonic acid. Treatment centers on correcting a double deficiency of B-6, zinc essential fatty acids and augmenting nutrients. It is believed to result from abnormal hemoglobin synthesis which depletes the body of these nutrients. A positive response often occurs within the first seven days of treatment, with 1-2 months usually required for correction of the imbalance.
4) High Copper (Hypercupremia)
If your level is above 140 mcg/dL, you would profit from getting rid of the excess copper. The most common depression phenotype for women. History of hyperactivity, tinnitus, and skin sensitivity to metals. Females with this condition usually have significant PMS and are prone to heightened depression during hormonal events such as puberty, gestation, childbirth and menopause. A woman's copper level more than doubles during the 9 months of pregnancy, apparently to enhance angiogenesis in the fetus. Women with an innate tendency for copper overload are prone to post-partum depression or post-partum psychosis. Estrogen increaases creuloplamin and copper levels and results in zinc depletion. Very elevated norepinephrine levels, elevated copper and low ceruloplasmin. Elevated norepinephrine/dopamine ratio. Most get worse after chocolate which is very high in copper. This condition is non-existant in males. Serum copper levels above 140 mcg/dl High NE and ADR levels can result from overmethlyation, probably genetic, elevated serum copper, and low folate/B12 levels. Hypertension is associated with high NE and ADR levels. Using folate/B12 will reduce hypertension and anxiety and depression. They often report a worsening of depression after estrogen or multiple vitamins. Most hypercupremics get worse if they overdose on chocolate. Treatment focuses on release of excess copper from tissues, promotion of copper excretion, and stimulation of metallothionein (a metal-binding protein). Many patients report a worsening for three weeks followed by steady improvement. Nutrient support is zinc, manganese, vitamin C and B6. Nutrients should be introduced gradually to avoid side effects. Use 25mg of zinc initially, then 50 then 75 as tolerated. A total of 60 to 90 days is usually required to correct this imbalance.
The list of things to avoid include the following:
1. Multiple vitamins/minerals containing Cu
2. Enriched foods with Cu added (learn to read the labels)
3. I recommend that she drink bottled water.
4. She needs to avoid swimming pools/jacuzzis treated with algicides containing copper sulfate.
5. The primary foods to avoid are chocolate, carob and shellfish.
5) Toxic Overload
This syndrome often involves a sudden, prolonged bout of depression without apparent reason and without a prior history of depression. Toxic substances which are capable of producing depression include lead, cadmium, mercury, and a wide variety of organic and inorganic chemicals. Treatment varies with the type of toxic material involved, and care must be exercised to avoid flooding the kidneys with toxins during the early stages of treatment. Heavy-metal overloads can be corrected quickly by in-hospital chelation, or more slowly using biochemical treatment. Organic chemical overloads require liberal use of antioxidants along with avoidance of the offending substances.
BTW, chocolate has 4 separate ingredients that can worsen malaise/depression in some people: (1) sugar, (2) caffeine, (3) copper, and (4) milk. The most significant of these for females is usually copper. Unfortunately carob has even more copper than chocolate.
Many depression patients experience striking cycles in which their depression may wax for months or wane for months. It's really hard to evaluate treatment efficacy for such persons since the patient may deteriorate during effective treatment or improve while experiencing placebo or a harmful therapy. (30 Dec, 2002)
Histamine assays for depression were introduced by Dr. Carl Pfeiffer of Princeton, NJ in the 1970' and 1980's. My clinic has found whole blood histamine to be very useful & has used this assay more than 30,000 times.
First of all, the analysis must be done for whole blood (not plasma, serum, etc), strictly adhering to the sampling protocol. We presently use LabCorp but in the past Quest also had proficiency for this assay.
The reference "normal" range for mental health is 40 to 70 ng/dL. Levels above 70 indicate undermethylation, whereas levels below 40 suggest overmethylation.
Undermethylated depressives thrive on l-methionine, calcium, magnesium, B-6, Zinc, and Vitamin C. In severe cases, up to 3,000 mg/day of methionine and 2,000 mg/day of Ca may be needed. However, we also like to routinely run a homocysteine test to assure the safety of the methylation protocol. This population is believed to result in low serotonin activity. This methylation therapy is quite slow in taking effect.... and often 6-8 weeks pass before
progress is obvious
Overmethylated (low-histamine) depressives thrive on folic acid, B-12, niacin (or niacinamide), B-6, Zinc, Manganese, DMAE, and Vitamins, C and E. In severe cases, up to 5,000 mcg/day of FA may be needed. Response is more rapid with this phenotype, with clear progress usually by week 4. This population is believed to have an innate tendency for elevated serotonin, dopamine, and norepinephrine levels.
This test can also help guide psychiatrists in selection of psychiatric medications. For example high histamine persons may do quite well on SSRI's, but low-histamine persons usually reactly very badly to SSRI's and are better candidates for benzodiazapines.
We like to augment the histamine blood test with an "absolute basophil" test offered by Direct Healthcare, Inc. The histamine assay can be affected by antihistamines and other medications with AH properties. The reference range for ABC's is 30-50.
We have an enormous chemistry database for depression..... more than 90 chemical assays for each of 3,200 persons with clinical depression. We find that 90% of depressives may be divided into five biochemical classifications, each requiring a different treatment approach. Two of these depression phenotypes are undermethylation and overmethylation. (June 2,
2003)
Estimated incidence of hypercupremia in our depressive population:
Females: 45%
Males: 3%
Overall: 30% (We have more females than males in our depression database)
As you can see from the numbers, hypercupremic depression is generally a female event. We are about to publish a database study which shows that hypercupremic feamles are especially prone to post-partum depression and post-partum psychosis. Many of these high-Cu females get worse on anti-depressants, but respond beautifully to nutrient therapy which normalizes Cu and Zn levels. (June 11, 2003)
