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Vitamin D and schizophrenia

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Dear Dr. Cannell:
 
My son has schizophrenia. Will Vitamin D help him? He started hearing voices twelve years ago and our lives have been a nightmare since then. He stayed with us for 8 years but we never knew when he would come home, when he was taking his meds, when he would become paranoid, and when he would lose his temper. He disappeared for weeks at a time and would show up at our door homeless and in trouble with the law. He became increasingly violent when he was home.
 
My husband and I had to have him arrested after he attacked his sister and he was eventually sent to prison, where he was finally made to take his medications. We feel so guilty about our role in sending him to prison but we were afraid for our lives.
 
I know he does not get sunlight in prison and the doctors there will not test his Vitamin D levels. They won’t let us send him supplements to take. Can the Vitamin D Council do anything about this?
 
Joanne, Sacramento, CA
 
Dear Joanne:
 
In my experience at Atascadero State Hospital, treating hundreds of patients with schizophrenia, adjuvant Vitamin D does not reduce hallucinations, paranoia, or psychosis but it does improve mood, reduce tremors, may reduce the amount of antipsychotic medications needed and helps prevent diabetes and the metabolic syndrome, which are common side-effects of “modern” antipsychotic medications. Care must be taken however, as the same cytochrome P-450 enzymes that metabolize Vitamin D are many of the same enzymes psychotropic medications utilize. Little or nothing is known about such Vitamin D and psychotropic drug interactions, thus Vitamin D levels are mandatory when treating Vitamin D deficiency in someone taking psychiatric medications.
 
As you are writing from Sacramento, I assume your son is incarcerated in the California Department of Corrections and Rehabilitation (CDCR). At my hospital, we get hundreds of schizophrenic patients per year directly from CDCR and I have yet to find one who was not Vitamin D deficient (> 50 ng/ml) and I have yet to find one who was prescribed Vitamin D by CDCR physicians. I find this ironic as CDCR is under a federal court mandate to improve the health care of inmates.
 
For those not familiar with schizophrenia, the course you describe is common, especially the pain and guilt schizophrenia inflicts on families. Schizophrenia is such a debilitating disease (losing your mind while knowing you are losing your mind) that about 10% of schizophrenics cure their disease by committing suicide. Of all the diseases I know, schizophrenia is the most vicious.
 
Recently, researchers at Harvard published an incredible paper.
Kinney DK, Teixeira P, Hsu D, Napoleon SC, Crowley DJ, Miller A, Hyman W, Huang E. Relation of schizophrenia prevalence to latitude, climate, fish consumption, infant mortality, and skin color: a role for prenatal vitamin d deficiency and infections? Schizophr Bull. 2009 May;35(3):582-95. Epub 2009 Apr 8.

What Drs. Dennis Kinney, Emerald Huang and colleagues did was nothing short of brilliant. I discussed their paper briefly several months ago in a newsletter but this month I want to spend the time this paper deserves.

Like autism, schizophrenia has strong genetic roots. However, just like autism, genetic predisposition is not predestination. That is, for reasons no one has yet understood, one identical twin will get schizophrenia but the other one has a 50% chance of escaping the disease; the identical twin concordance rate is about 50%. This implies an environmental trigger.

We can get a clue to that trigger by looking at identical twins and multiple sclerosis. Although their genes are identical, the identical twin that went out in the sun when young was much less likely to get multiple sclerosis than his or her identical twin. For example the adolescent identical twin who listened to the dermatologists, and avoided sun tanning, was 2.5 times more likely to later get MS than his/her identical sibling who ignored the dermatologists and tanned. (I predict similar studies will be published concerning identical twins in both autism and schizophrenia.)

Islam T, Gauderman WJ, Cozen W, Mack TM. Childhood sun exposure influences risk of multiple sclerosis in monozygotic twins. Neurology. 2007 Jul 24;69(4):381-8.
Unlike autism, schizophrenia takes about 25 years to manifest itself; as Professor Robert Heaney would say, it is a long-latency disease. That is, the average age of onset until recently was about 25, which explains why the incidence of schizophrenia has not yet dramatically increased. In fact, autism used to be called infantile schizophrenia and it seems likely, as the current crop of autistic children ages, some will later be re-diagnosed with schizophrenia.

Recent studies, as compared to studies published in the 1980s and 1990s, show schizophrenia is increasing, especially among teenagers. In fact, all of the studies I could find published in the 21st century, as opposed to earlier studies, show schizophrenia is increasing:

Boydell J, Van Os J, Lambri M, Castle D, Allardyce J, McCreadie RG, Murray RM. Incidence of schizophrenia in south-east London between 1965 and 1997. Br J Psychiatry. 2003 Jan;182:45-9.

Preti A, Miotto P. Increase in first admissions for schizophrenia and other major psychoses in Italy. Psychiatry Res. 2000 May 15;94(2):139-52.

Tsuchiya KJ, Munk-Jørgensen P. First-admission rates of schizophrenia in Denmark, 1980-1997: have they been increasing? Schizophr Res. 2002 Apr 1;54(3):187-91.
(If you want to read something scary, read this article about two large US government autism studies about to be released. In ten years you will be reading the same story about schizophrenia)

Kirby D. Autism Rate Now at One Percent of All US Children? Huffington Post; 08/11/09

Before I describe the remarkable paper from Harvard, I want to compliment researchers at the Saint Barthomew’s Hospital in England for almost saying what most psychiatrists already know; the incidence of schizophrenia is much higher in people with dark skin. In the 1970s and 80s, that was an accepted fact, until charges of racism were leveled against the American Psychiatric Association (APA). The spineless APA promptly did retrospective chart analyses and announced the incidence of schizophrenia is exactly – precisely – the same for Blacks as it is for Whites. The ethnicity question is important as the Vitamin D theory is not tenable unless darker skin means a higher incidence.

Coid JW, Kirkbride JB, Barker D, Cowden F, Stamps R, Yang M, Jones PB.
Raised incidence rates of all psychoses among migrant groups: findings from the East London first episode psychosis study. Arch Gen Psychiatry. 2008 Nov;65(11):1250-8.

Actually, in 2007, a group at Columbia University appears to be the first to break with the APA’s political correctness. Dr. Michaeline Bresnahan and her colleagues followed 12,000 children for up to 28 years after birth. African Americans were 3 (three) times more likely to develop schizophrenia than whites and socioeconomic factors could not explain away their findings.

Bresnahan M, Begg MD, Brown A, Schaefer C, Sohler N, Insel B, Vella L, Susser E. Race and risk of schizophrenia in a US birth cohort: another example of health disparity? Int J Epidemiol. 2007 Aug;36(4):751-8.

Getting back to the Kinney et al paper, they examined 188 studies to find 49 studies that used similar diagnostic methods. The authors were quite strict on only looking at the 49 studies that used similar diagnostic criteria as the authors are aware that most psychiatrists dismiss any latitudinal variation in the prevalence of schizophrenia by saying that doctors around the equator are too stupid to make a correct diagnosis of schizophrenia.

Then, the authors explored the three most common theories for the environmental trigger of schizophrenia:

1.      Poor prenatal care,
2.      Low omega-3 fatty acid consumption,
3.      Prenatal exposure to infections, especially influenza.

First, they found a 10 (ten) fold variance in the prevalence of schizophrenia in the world, from a high of 28 cases per 1000 in Oxford Bay, Canada, near the Arctic Circle, to a low of 1 per 1000 around the equator, confirming Dr. E.F. Torrey’s landmark latitudinal findings published in 1987. Kinney et al confirmed that latitude and cold climate broadly and strongly determine the prevalence of schizophrenia. The majority of the 49 studies the authors reviewed were completed before the sun scare, which has driven many equatorial mothers out of the sun, so I predict the incidence of schizophrenia around the equator will soon be increasing.

Second, if you were born in countries around the equator with high infant mortality (a proxy for poor prenatal care), the incidence of schizophrenia was very low. In other words, around the equator it didn’t matter if you had poor prenatal care, you still did not get schizophrenia. But, at latitudes away from the sun, prenatal care did matter, and it mattered more and more the further you got from the equator. It appears that high maternal Vitamin D levels around the equator overwhelmed the effect of poor prenatal care.

Third, around the equator, it did not matter if mothers ate Vitamin D-containing fish; it only mattered the further you got away from the equator. That is, latitude overwhelmed the effect of fish consumption; consumption of Vitamin D containing fish only began to matter when the sun was not available to make Vitamin D. If omega-3 fatty acid consumption was the cause of schizophrenia, latitude variation in omega-3 consumption would not matter.

Fourth, they found that skin color only mattered away from the equator, that is, in the very dark-skinned equatorial Indians and equatorial Africans, skin color hardly mattered; the prevalence of schizophrenia was quite low. However, the further poleward you live, dark skin preventing maternal Vitamin D production becomes an increasingly significant risk factor for schizophrenia.

The authors could not dismiss the influenza theory of schizophrenia, but as I hope readers are aware, the association between influenza and schizophrenia is probably mediated by vitamin D. That is, influenza is a symptom of Vitamin D deficiency:

“… the characteristic microbe of a disease might be a symptom instead of a cause.”
George Bernard Shaw
(Preface on Doctors, The Doctor’s Dilemma, 1911)

Kinney et al concluded that the Vitamin D hypothesis correctly predicted the associations between prevalence and skin color, fish consumption, infant mortality, latitude and temperature. The Vitamin D effect “overwhelms” the effects of other known risk factors. That is, maternal Vitamin D deficiency is not just “a” cause, but is probably “the” cause of schizophrenia.

I love epidemiological studies like this, and I’m sure Professor John McGrath in Australia does as well. It was McGrath who first hypothesized that gestational Vitamin D deficiency causes schizophrenia. I often despair that I have had to wait two years for the world to learn autism is triggered by gestational and early childhood Vitamin D deficiency. John McGrath has had to wait 10 years for his theory to be accepted and will probably still be waiting 10 years from now.

McGrath J. Hypothesis: is low prenatal vitamin D a risk-modifying factor for schizophrenia? Schizophr Res. 1999 Dec 21;40(3):173-7.

I’d like to add one prediction to McGrath’s theory. The Vitamin D theory of schizophrenia predicts that the age of onset of schizophrenia should be getting younger. That is, as more pregnant women listened to dermatologists, their children are not only more likely to develop schizophrenia, but are more likely to develop more severe cases that present at a younger age. That is exactly what appears to be happening.

Di Maggio C, Martinez M, Ménard JF, Petit M, Thibaut F. Evidence of a cohort effect for age at onset of schizophrenia. Am J Psychiatry. 2001 Mar;158(3):489-92.

Ajdacic-Gross V, Lauber C, Warnke I, Haker H, Murray RM, Rössler W.

Changing incidence of psychotic disorders among the young in Zurich. Schizophr Res. 2007 Sep;95(1-3):9-18. Epub 2007 Jul 16.

Dr. John Cannell, MD

Vitamin D Council

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