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Dirt, Disease, Depression, and the Imprinted Brain Theory

Major depression may not be a mental disorder, but an immunological one.

Diseases of Modern Environments Symposium
Source: Diseases of Modern Environments Symposium

According to the so-called Hygiene Hypothesis, our modern environment with its washed food, treated water, and eradication of worms and other parasites means that we have lost the once-ubiquitous environmental micro-organisms which previously trained and tuned our immune system. These endemic “old friends” meant that genes duplicating their immunity-training-and-tuning function were lost in much the same way that we lost our gene for synthesizing vitamin C: our ancestors found so much of that vitamin in the fruit they predominantly ate that they could get by without the gene for it!

Unfortunately though, this means that some individuals in modern societies suffer the effects of this loss of out-sourced regulation of the system and mount immune responses to harmless environmental antigens (asthma), foods (inflammatory bowel disease), or self-antigens (auto-immune diseases like multiple sclerosis or type 1 diabetes). At the very least, this explains why children brought up on farms, who have male siblings or faeco-oral infections and/or worms suffer from these immuno-regulatory disorders much less—not to mention why hay fever was at first regarded as a disease of the elite (and is certainly less prevalent among farmers).

But the hygiene hypothesis may be able to explain another disease of modernity: major depressive disorder (MDD). This currently ranks fourth in the global burden of disease but will probably be second by 2020, and is strongly associated with a Western life-style. Patients with MDD have symptoms of inflammation (including elevated cytokines: immune-system signalling and regulating molecules). Up to 50% of patients receiving interferon to boost immunity develop MDD, and even more have depressive symptoms. MDD is found along with auto-immune disorders such as type 1 diabetes, irritable bowel syndrome, eczema, and asthma, and anti-depressants are also anti-inflammatory. Indeed, a soil bacterium with anti-depressant-like effects in animals administered to cancer patients reduced cytokine-induced symptoms that resemble depression and also improved anxiety and depressive symptoms in lung cancer chemotherapy patients.

If all this is true, it has immense implications for psychiatry because it implies that MDD is not strictly speaking a mental illness at all—that is, one resulting from an unbalanced brain—but is in fact a mental symptom of a dysregulated immune system. Furthermore, it implies that the most effective therapy is likely to be similar to those suggested by the hygiene hypothesis for other immune-related disorders—and is certainly not likely to be psychotherapy. Worms might do you more good! And of course, the hygiene hypothesis explains the rising incidence of MDD.

Finally, seeing MDD as an immuno-regulatory disorder of the modern environment rather than as a true mental illness also solves a major paradox for the imprinted brain theory. The theory’s distinctive diametric model of mental illness proposes that autism spectrum disorders (ASDs) are the opposite of psychotic spectrum disorders (PSDs), as I have explained in previous posts. A provocatively counter-intuitive prediction of the theory is that if ASDs are increasing as they are, PSDs should be falling (because the risk factors for ASD are protective against PSD, and vice versa). And there is good evidence that psychotic disorders are indeed falling. Bleuler, who gave us schizophrenia, noticed that its symptoms were getting milder in the 20th century, and others have asked where all the catatonics have gone. First-admission schizophrenia in Scotland has fallen by 57%, in Denmark and New Zealand by 37%, and by 42% in Canada where there was a 52% decrease in annual inpatient prevalence rates 1986-1996 with no corresponding change in outpatient rates. Nevertheless we have seen that MDD is remorselessly rising. My personal view is that the hygiene hypothesis explains it, and that therefore the increase in MDD constitutes no kind of refutation of what is, after all, a theory about imbalances in the brain—not in the immune system.