Urine Test for Schizophrenia

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Discovery of a Urine Test for Schizophrenia.

 

Journal of Orthomolecular Medicine: The Discovery of Kryptopyrrole and

its Importance. Vol. 10, No. 1, 1995

 

The Discovery of Kryptopyrrole and its Importance in Diagnosis of

Biochemical Imbalances in Schizophrenia and in Criminal Behavior

 

by Abram Hoffer, M.D., Ph.D.

 

In this issue (JOM, Vol 10, No 1) Dr. Richard T. Kraus describes a

notorious serial killer who is serving a 250 year sentence for the

murder of eleven women. Unfortunately, serial killers are not a

threatened species. On the contrary, they threaten society more and

more, and with modern weapons of destruction seem to be even more

effective. This case report may be the first in which four main

factors which determine human behaviour are discussed in detail. Dr.

Kraus describes " ...a matrix of genetic, biochemical, neurological and

psychological deficits " . I am particularly interested because the

kryptopyrrole ( " kp " ) which was found in this person's urine was

originally discovered in Saskatchewan about 1960 when I was Director

of Psychiatric Research. The main biochemical research was completed

in Saskatchewan by Dr. D. Irvine,(1) and in New Jersey by Dr. C. C.

Pfeiffer (1) and his research group of biochemists.

 

This report provides a model of how criminal behaviour ought to be

explored, with numerous references to the medical literature for all

of the four variables. I will discuss mainly the biochemical findings

and provide a brief history of its discovery. The presence of kp in

urine is a valuable diagnostic aid especially for determining more

specific treatment. It is most closely related to the schizophrenias

but cuts across all diagnostic categories. I think it could become an

important differential diagnostic test. It is simple to do, any

competent medical laboratory can do it. The laboratory in Victoria has

been

running them for me since 1976.

 

By 1960 the biochemical unit of the psychiatric research program in

Saskatchewan was gearing up to investigate any possible relationships

to the schizophrenias. One of the studies involved examining urine for

several fractions and comparing the urine of patients and controls. We

were then treating many alcoholics using psychedelic therapy.

D-lysergic acid diethylamide (LSD), the hallucinogen, was well studied

as a compound which could induce a model psychosis or a

psychotomimetic experience. It occurred to me that inasmuch as LSD

produced something very similar (but not identical with)

schizophrenia, perhaps it might also generate in the body of a person

(not schizophrenic) the same type of biochemical abnormality which we

thought was present in the patients. I asked Dr. N. Payza to examine

the samples of urine obtained from an alcoholic who had been given LSD

as part of his treatment.

 

The first morning specimen was obtained and another one around noon,

usually the height of the experience. My idea was that if something

appeared after LSD which was not present before, this might give as a

lead. We were fortunate because the first patient we tested had a

large amount of a substance that was not present in the morning

specimen. We soon showed that it was not a breakdown product from the

LSD itself, which meant it was created in the body by the impact of

the hallucinogenic drug upon one of the biochemical systems. After we

had improved the assay procedure we began to test patients. One day I

took into the laboratory 12 specimens of urine. Six were obtained from

schizophrenic patients, five were obtained from normal subjects and

one was a blank. The code was kept secret. I asked the biochemical

team to analyze these samples and to tell me which of the 12 were

obtained from the schizophrenic patients. They accurately spotted all

the schizophrenic samples. I concluded that schizophrenic patients,

not given LSD, had the same substance in their urine as did some

alcoholics who had been given LSD, but that it was not present in

normal controls.

 

We needed large amounts of material for our chemical studies.

Fortunately for us a chronic schizophrenic woman on the ward had huge

quantities of this product. For a moment we considered calling the

compound the Jensen factor. At first we called it the unknown

substance (US), and later the mauve factor because when developed on

the paper chromatogram it stained a beautiful mauve. When it was

identified we called it, more accurately, kryptopyrrole. We named the

disease characterized by large amounts of mauve factor " malvaria, " but

Dr. Pfeiffer later gave it the more appropriate term pyrolleuria.

 

I immediately started two lines of investigation: (1) by Dr. Payza for

short time, and then by Dr. D. Irvine who continued the research first

at the Research Laboratory at the Saskatchewan Hospital in North

Battleford, and later at University Hospital in Saskatoon. The

objective was to determine the structure of the substance and its

source. (2) To study its clinical correlates, i.e. could it be used to

assist in diagnosis, could it have therapeutic significance, and could

it be used to follow patients both to determine if they were

improving, and to determine if they were getting worse.

 

Dr. Irvine showed that it was a pyrrole, later identified as

kryptopyrrole. We began to cooperate with Dr. C. C. Pfeiffer at

Princeton, New Jersey. Dr. H. Osmond, my colleague in the earlier

Saskatchewan research, was then Director of Research for the state.

The two laboratories did the basic work. Dr. Pfeiffer and his team

discovered how to measure the amount of this substance in the urine

using a fairly simple test, and they showed that this substance bound

with pyridoxine and zinc and when present in large amounts produced a

double deficiency of this vitamin and the mineral. On the clinical

side he described the syndrome pyrolleuria, a form of schizophrenia

with clearly marked out symptoms and signs which could be diagnosed by

the present of kp in the urine.

 

Several years later we had examined thousands of patients at three

hospitals for the mauve factor.(2) It was present mostly in

schizophrenic patients but was also present in one-quarter of other

non schizophrenic patients including depressions, alcoholics, anxiety

states, and in children with learning and behavioral disorders. It was

rarely present in normal subjects, and was present in ten percent of a

non psychiatric stressed population drawn from the surgical wards of

the hospital. To my surprise it was found in most cases of lung

cancer.(3) I found the following relationships:

 

1) Relationship to diagnosis - The mauve factor was found in the

following categories of patients:

 

Diagnosis; percent with the diagnosis mauve factor

 

Normal subjects 0

 

Physically ill

Adults 10

Children 10

Mood disorders 20

Alcoholics 20

 

Schizophrenics

Early, not treated 75

Recovered 0

Not recovered 50

 

Thus it was clear that although it was most closely related to the

schizophrenic

population, it could not be considered a test for schizophrenia.

Probably there will never be such a test since the clinical diagnosis

is subjective and there is wide disagreement among clinicians about

the diagnosis. I therefore compared the results of testing for this

compound with the results obtained on the HOD (Hoffer-Osmond

Diagnostic) test.

 

2) Relationship to HOD Test.(4) This is a card sort test similar in

principle to the MMPI but containing entirely different questions.

Perceptual symptoms including hallucinations and illusions are

specifically covered. The HOD test can be described as a perceptual

test. Patients sorted 145 cards into true and false piles and these

were recorded and scores obtained. We standardized this test on

thousands of subjects and have reported the results widely. We found

that there was a better relationship between the presence of high

scores in the test and the presence of kp in the urine than there was

between kp and clinical diagnosis. Schizophrenics had much higher

scores than did any other group of psychiatric patients, with the

exception of patients with delirium tremens and normal subjects

undergoing the LSD experience. In one study in New York, the

investigating team found that the admission HOD test results were more

closely correlated to the final discharge diagnosis than they were to

the admitting diagnosis, even though none of the clinicians were able

to see the results of the HOD test.

 

3) As an indicator for treatment. By 1960 we had completed four double

blind controlled prospective studies on schizophrenic patients

comparing niacin, niacinamide and placebo.(5) Based upon these studies

and upon open clinical studies going back to 1951, I had concluded

that schizophrenic patients responded better to any treatment when

they were given adequate doses of vitamin B3. Forty years later this

is still my conclusion, as it is of every physician who uses the same

treatment. The only physicians who disagree are those who have never

used the treatment and who have even refused to examine earlier

studies. There is no patent on vitamin B3, and without a patent there

is no financial incentive for any company to promote this treatment.

Since schizophrenic patients, most of whom had the factor in their

urine, responded better when treated with vitamin B3, I concluded that

any psychiatric disease, no matter what they were diagnosed

clinically, might also do better with this vitamin. This was confirmed

by a large series of open clinical studies. I will not term these

studies anecdotal, which has become the politically correct term for

denigrating any studies that are not double blind, since all clinical

studies depend upon the history or herstory of patients and how they

respond, i.e. upon anecdotes. The only difference is that in double

blind studies the anecdotes are collected by physicians or others who

are blinded by not knowing what treatment is being given. At least

this is the theory of this type of procedure. In fact, the vast

majority of these studies are so imperfectly blinded that few

clinician or nurses have much difficulty deciding whether the patient

was on placebo or something more active.

 

Worshippers of the double blind remind me of the emperor whose

nakedness was seen only by a child not yet blinded by tradition. This

report by Kraus is an excellent example of the type of anecdotal

history which has contributed so much to medicine.

 

The presence of the mauve factor in urine became a valuable indicator

to use vitamin B3. Later, when Dr. C. C. Pfeiffer showed that kp bound

pyridoxine and zinc and described the syndrome pyrolleuria, this

became another important indicator that vitamin B6 and zinc must be

used. It is especially valuable for children, who are very difficult

to diagnose because they vary so much one from the other.

 

4) Response to treatment. Patients who responded to treatment

invariably became mauve factor or kp factor negative. However, there

were many patients who no longer excreted this factor but who had not

recovered. I have not examined whether these patients might have

responded to longer treatment. In my recent report (6) on chronic

patients it is evident that many chronic patients need five to seven

years of treatment. Perhaps some of the negative excretors after

having been positive might have fallen into this group. Patients who

were well and were kp free were followed for months or years. If they

became positive at any time they also became clinically ill within a

matter of weeks or months.

 

Generally, the presence of kp is associated with clinical conditions

characterized by a high degree of perceptual disorganization. These

are chiefly the schizophrenic patients, but also includes a

substantial proportion of other psychiatric diseases also

characterized by perceptual changes. Unfortunately psychiatrists do

not search their patients' mental state adequately and miss many of

these changes. They can be readily detected using perceptual tests

such as the HOD test. (7) In other words, the presence of kp

correlates strongly with high scores on these perceptual tests.

Perhaps Dr. Kraus's detailed report will arouse interest in this test,

sadly neglected for so many years.

 

In 1960 I examined a seven year old boy who had been diagnosed

retarded and preparations were being made to send him to a special

school. His parents were very concerned and asked me whether I would

examine him. For over a year he had difficulty in school, could not

read, and avoided going to school as much as he could, often staying

away from home all day but not at school. His mother, a teacher, had

been spending a lot of time giving him special instruction without

improvement. He was also developing behavioral problems at home. I

examined him early in 1960 and could not locate any particular

problem, perhaps because I had not had much experience treating

children. I then had his urine analyzed for mauve factor, kp, and to

my surprise found a large amount. I called his father, a friend of

mine, and said in jest " You are in luck, your son has schizophrenia. "

He answered, " Why does that make me so lucky? " I then told him I was

kidding him, and added seriously he was certainly not schizophrenic,

but since he had the same biochemical factor in his urine we had found

in schizophrenics, and since they had responded well to vitamin

therapy, this suggested that his son might respond in a similarly

beneficial way.

 

I started him on niacinamide 1,000 milligrams after each meal. In the

fall his father asked me would I like to know what had happened to his

son. He then told me that two months after his son had started on the

vitamin he had begun to read, that he had spent a few months reading

voraciously and that he was no longer concerned about his behaviour.

His son was normal and remained well. He took his niacinamide

regularly until he was about 14. One day he asked his mother why he

was taking the pills. She brought him to see me and I explained why I

thought he should remain on the vitamin until at least age 18 at which

time he could determine how well he could do without it. He is still

well, happily married with children, and is fully employed in a

responsible job.

 

This illustrates the use of the kp urine test for pyrolleuria, and the

use of niacinamide in large doses to treat this condition

successfully. I did not use vitamin B6 nor zinc in 1960. Pyridoxine is

essential for the conversion of tryptophan to nicotinamide adenine

dinucleotide, the vitamin B3 coenzyme. With a deficiency of

pyridoxine, the synthesis of NAD in the body is reduced. A pyridoxine

deficiency will produce a form of pellagra not distinguishable

clinically from the pellagra caused by a deficiency of vitamin B3.

 

References

Hoffer A: The Presence of Malvaria in Some Mentally Retarded Children.

Amer J Ment Def 67:730-732, 1963. Hoffer A: Malvaria and the Law.

Psychoso-matics, 7:303-310, 1966.

 

Hoffer A: A Program for the Treatment of Alcoholism: LSD, Malvaria and

Nicotinic Acid. In, The Use of LSD in Psychotherapy and Alcoholism.

Ed. HA Abramson.Bobbs-Merril, New York, 343-402, 1967.

 

Hoffer A & Mahon M: The Presence of Unidentified Substances in the

Urine of Psychiatric Patients 2:331-362, 1961

 

Hoffer A & Osmond H: The Relationship Between an Unknown Factor (US)

in the Urine of Subjects and HOD Test Results. J Neuropsychiatry

2:363-368, 1961.

 

Hoffer A & Osmond H: Malvaria: A New Psychiatric Disease. Acta

Psychiat Scand 39:335-366, 1963.

 

Hoffer A: The Psychophysiology of Cancer. J Asthma Research 8:61-76, 1970.

 

Hoffer A & Osmond H: A Card Sorting Test Helpful in Making Psychiatric

Diagnosis. J Neuropsychiatry 2:306-330, 1961.

 

Hoffer A & Osmond H: A Card Sorting Test Helpful in Establishing

Prognosis. Am J Psychiatry 118:840-841, 1962.

 

Hoffer A & Osmond H: The Relationship Between an Unknown Factor (US)

in the Urine of Subjects and HOD Test Results. J Neuropsychiatry

2:363-368, 1961.

 

Hoffer A & Osmond H: The Association Between Schizophrenia and Two

Objective Tests. Can Med Ass J 87:641-646, 1962.

 

Hoffer A, Kelm H & Osmond H: The Hoffer-Osmond Diagnostic Test. RE

Krieger Pub Co. Huntington, New York, 1975.

 

Hoffer A, Osmond H, Callbeck MJ & Kahan I: Treatment of Schizophrenia

with Nicotinic Acid and Nicotinamide. J Clin Exper Psychopathol

18:131-158, 1957.

 

Hoffer A: Niacin Therapy in Psychiatry. C.C.Thomas, Springfield, IL, 1962.

 

Hoffer A & Osmond H: Treatment of Schizophrenia with Nicotinic Acid -

A Ten Year Follow-Up. Acta Psychiat Scand 40:171-189, 1964.

 

Hoffer A: Treatment of Schizophrenia with a Therapeutic Program Based

Upon Nicotinic Acid as the Main Variable. Molecular Basis of Some

Aspects of Mental Activity, Vol II. Ed. O Walaas, Academic Press, New

York, 1967.

 

Hoffer A: Megavitamin B-3 Therapy for Schizophrenia. Can Psychiatric

Assoc J 16:499-504, 1971.

 

Hoffer A: Treatment of Hyperkinetic Children with Nicotinamide and

Pyridoxine. Can Med Assoc J 107:111-112, 1972.

 

Hoffer A: Natural History and Treatment of Thirteen Pairs of Identical

Twins, Schizophrenic and Schizophrenic-Spectrum Condi-tions. J

Orthomolecular Psychiatry 5:101-122, 1976.

 

Hoffer A: Orthomolecular Medicine for Physicians. Keats Pub, New

Canaan, CT, 1989.

 

Hoffer A: Orthomolecular Medicine. In, Molecules In Natural Science

and Medicine, An Encomium for Linus Pauling. Ed Z.B. Maksic & M.

Eckert-Maksic, Ellis Horwood Ltd, Chichester, West Sussex, England, 1991.

 

Hoffer A: Vitamin B3 and Schizophrenia: Discovery, Recovery,

Controversy. Quarry Press, Kingston, Ontario, 1994.

 

Hoffer A: Chronic Schizophrenic Patients Treated Ten Years Or More. J.

Orthomolecular Medicine, 9:7-37, 1994.

 

Hoffer A & Osmond H: How To Live With Schizophrenia. University Books,

New York, NY, 1966. Also published by Johnson, London, 1966. New and

Revised Ed. Citadel Press, New York, N.Y. 1992

 

Hoffer A & Osmond H: The Hallucinogens. Academic Press, New York, 1967.

 

Orthomolecular Psychiatry, Eds. D. Hawkins and Linus Pauling. W.H.

Freeman and Co., San Francisco, 1973.

 

(Also see References in Dr. Richard T. Kraus' paper.)

 

Reprinted with permission of the author.

 

A. Hoffer, M.D., Ph.D.

#3A - 2727 Quadra Street

Victoria, B.C. V8T 4E5