Is Schizophrenia an Inflammatory Illness?

madness of adam and eve

The Madness of Adam and Even: How Schizophrenia Shaped Humanity

by David Horrobin (2001 Bantam Press)

Book Review

The Madness of Adam and Eve advances a dual hypothesis: 1) that schizophrenia is a whole body disorder, rather than a “brain disease, as promoted by Big Pharma and the psychiatric fraternity and 2) that schizophrenia stems from the same series of genetic mutations that led to the appearance of the human species (homo sapiens) 100,000 years ago.

The specific biochemical “error” Horrobin credits for causing schizophrenia is a defect in the metabolism of arachidonic acid (AA), a fatty acid that facilitates smooth signal transmission between nerve endings. Horobin believes a genetic mutation around 100,000 years ago caused a massive increase in AA production, enabling a giant increase in dendritic connections between neurons. This, in turn, resulted in a sudden explosion in human intellectual capacity, as well as the sudden appearance of art, music and organized religion.

Horribin also maintains that schizophrenia was a relatively mild illness in hunter gatherer societies, owing to a diet rich in the omega 3 fatty acids essential for optiminal brain function. With the major dietary changes that accompanied the agricultural and industrial revolution, schizophrenia has become much more severe. The switch from omega 3 and omega 6 fatty acids to saturated animal fat was by far the most significant, as saturated fats can suppress the uptake and utilization of omega 3 fatty acids.

Horrobin’s hypothesis is born out by WHO research revealing that schizophrenia is more severe in the industrialized west, studies showing that schizophrenics improve when given large doses of the omega 3 fatty acid EPA, and the failure of schizophrenics to experience a “niacin blush”* when exposed to megadoses of niacin.

Aimed at a lay audience, The Madness of Adam and Eve doesn’t always distinguish clearly between theory and established fact. While Horribin’s ideas make an important contribution to the understanding of mental illness, his overemphasis on genetic determinism in the origin of mental illness is clearly dated. In 2002, the field of epigenetics** was still in its infancy and there was limited understanding of the role of noxious prenatal influences on gene expression and the development of chronic physical and mental illnesses. Nor was the role of harmful intestinal bacteria and endotoxin-related inflammation recognized in the etiology of autism, schizophrenia and depression.

His portrayal of the intellectual inferiority of Homo neanderthalensis (Neanderthal man) is also obsolete. More recent archeological evidence suggests that Neanderthal man was the intellectual equal of homo sapiens.

*A niacin flush is sudden reddening and burning of the skin caused when niacin promotes conversion of AA to the inflammatory peptide prostaglandin. Several researchers have proposed using a niacin skin test as a research tool in studying schizophrenia.

**Epignetics is the study of hormonal and other prenatal influence that affect the expression of genes as specific protein enzymes.

When Horrobin died in 2003, the British Medical Journal wrote a particularly nasty obituary describing him as “the greatest snake oil salesman of his age.” A decade of research into the beneficial role of omega 3 oil in the treatment of depression (particularly post natal depression, bipolar illness, schizophrenia and premenstrual syndrome) has clearly vindicated him. The supplementation of prescription psychotropics with omega 3 oils is now standard psychiatric practice. 

Research into his theory that schizophrenia is a whole body inflammatory illness, rather than a brain disease, is also advancing. More recent studies focus on inflammation caused by endotoxin-producing by gram negative intestinal bacteria. Thus far schizophrenics’ demonstrated impairment in prostaglandin synthesis has failed to translate into viable treatment options.

There have been numerous studies suggesting a beneficial effect of non steroidal anti-inflammatory (NSAID) medication (such as ibuprofen and naprosyn) in the treatment of schizophrenia. Unfortunately NSAIDs, like psychotropics, have numerous serious side effects, including peptic ulcer disease and reduced kidney function.

 

Medicalizing the Menstrual Cycle

pmd

I have blogged previously (see Menopause: Made in the USA) about the negative effects of the “corporatization” of health care in the US. “Disease mongering” is a particularly nasty one. This occurs when pharmaceutical companies “medicalize” common conditions in order to market drugs that supposedly treat them.

Thanks to skillful marketing, Eli Lilly has turned premenstrual syndrome (PMS) into a profit-making commodity nearly as lucrative as menopause and “childhood bipolar disorder” (see Drug Companies: Killing Kids for Profit).

In 1994, the American Psychiatric Association (APA) included premenstrual dysphoric disorder (PMDD) in their diagnostic manual “as a possible mental disorder requiring more research.” They have continued the diagnosis in DSM V. Although DSM IV lists PMDD as a strictly “research” diagnosis, Eli Lilly immediately seized on it as a genuine disorder and devised a marketing strategy to profit from it.

The Difference Between PMS and PMDD

Approximately 80-90% of women worldwide report physical and emotional changes in the 7-10 days prior to the onset of menstruation. For most women, these consist of minor physical changes similar to those of early pregnancy (water retention, breast swelling and tenderness and abdominal bloating).

Approximately 1/3 of women note mental and emotional changes (aka PMS) – depression, anxiety, fatigue, irritability, insomnia, difficulty concentrating – that have a minor impact on their daily functioning.

Although the APA has yet to agree PMDD even exists as a disorder, there are numerous claims in psychiatric and women’s health literature that approximately 3-8% of women suffer from it. By definition, a woman can only qualify for a PMDD diagnosis if they experience a “marked” decrease in normal functioning due to premenstrual mood changes. A rigorous Swedish study ascertained that the true percentage of women experiencing a “marked” decrease in functioning before their period closer to 1.3%.

A Golden Marketing Opportunity for Eli Lilly

Once the patent on a drug expires, other manufacturers are free to produce cheaper generic versions, resulting in plummeting sales of the original brand name drug. In 1999 Lilly, facing the expiration of its patent on Prozac, exploited the new “diagnosis” of PMDD by re-branding Prozac as a feminine pink and purple tablet called Sarafem.

In 2001, the FDA approved Sarafem for “PMDD,” on the basis of double blind studies involving several hundred women. Lilly reported a 60% response rate in women who took it for five cycles, with greater effectiveness in women who took it continuously throughout the month (as opposed to 7-10 days before their period).

Hopefully psychiatrists aren’t quite so gullible as the FDA, given Prozac’s limited effectiveness in treating depression. Thirty years of double blind studies reveal that depressed patients who take Prozac have an average response rate of 38-40%. In fact, statistical analysis of all randomized controlled trials reveal that all SSRI’s (i.e. Prozac, Zoloft, Paxil, citalopram, etc) are only slightly more effective than a placebos, which works 33-37% of the time.

Skillful Marketing Adds Billions to US Health Care Bill

Charging three dollars per dose for their pink and purple Sarafem tablets (in contrast to 41 cents per dose for generic fluoxetine), Lilly launched a massive marketing campaign to convince women they suffered from PMDD. In 2001, the year Serafem came out, nearly 100,000 prescriptions were sold, reaping Lilly $85 million in profits.

Given the soaring cost of health care in the US (the main reason millions of Americans go without medical care), it strikes me as unethical and immoral to trick doctors and women into wasting nearly a billion dollars on pink and purple pills with a fancy name, when generic fluoxetine would have been equally effective at 1/9 the cost.

Research Evidence for “Natural” Treatments

What I find really fascinating about the PMS/PMDD controversy is that it’s one of the few women’s health “conditions” in which there are more double blind placebo trials of “alternative” or “natural” treatments than medication trials. The three “alternative” treatments that have shown clear effectiveness in randomized controlled trials are omega 3 supplements, Vitamin D and the chaste tree berry or chasteberry. In fact, much of this research suggests that PMS-related mood changes may actually represent a nutritional deficiency of omega 3 and/or Vitamin D.

Omega 3 oil is the most studied in PMS-related mood changes, largely owing to its proven efficacy in depression and large cross cultural studies revealing that populations (for example Asians and Norwegians) consuming large amounts of fish (a primary source of omega 3) in their diets have an extremely low incidence of depression.

Vitamin D, has also proved helpful for depression in double blind studies, especially in elderly depressives suffering from documented Vitamin D deficiency. Other studies show that 1,000 – 2,000 international units of Vitamin D is helpful in alleviating premenstrual symptoms.

This finding correlates with an extremely low incidence of PMS in Asian women. The same oily fish that are a rich source of omega 3 are the only natural food source of Vitamin D (the majority of us derive Vitamin D from exposure to sunlight).

Three double blind studies in the British Medical Journal, the Archives of Gynecology and Obstetrics and the Journal of Women’s Health and Gender-based Medicine reveal that chasteberry helps approximately 52% of women with PMS. Chasteberry is an herbal remedy used by Hippocrates in ancient Greece for pre-menstrual symptoms. It’s believed to work by lowering prolactin (a pituitary hormone influencing milk production). High prolactin levels are a recognized, but infrequent, cause of depression.

Take Home Message: Try Natural Remedies First

In light of all the above studies, common sense would dictate that women who suffer from PMS should try a combination of omega 3 and 1,000-2,000 IU of Vitamin D for a minimum of six months before resorting to either Sarafem or generic fluoxetine. Both have potentially serious long term side effects. Owing to their effect on serotonin receptors in the brain, SSRI’s can be very difficult to stop. Moreover they are associated with a loss of bone density, which increases the risk of osteoporosis and hip fracture in later life, and possibly linked to breast and ovarian cancer

photo credit: taberandrew via photopin cc