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Inflammation's possible role in psychiatric disorders

Unlikely as it may seem, #inflammation has become a hashtag. Rather than simply being on our side, fighting infections and healing wounds, it turns out to have a dark side as well: the role it plays in causing us harm, writes Professor Edward Bullmore head of the department of psychiatry at Cambridge University in The Guardian. Medical minds are now opening up to the idea that inflammation could be as widely and deeply implicated in brain and mind disorders as it is in bodily disorders.

He writes that it’s now clear that inflammation is part of the problem in many, if not all, diseases of the body. And targeting immune or inflammatory causes of disease has led to a series of breakthroughs, from new treatments for rheumatoid arthritis and other auto-immune diseases in the 1990s, through to the advent of immunotherapy for some cancers in the 2010s. Even more pervasively, low-grade inflammation, detectable only by blood tests, is increasingly considered to be part of the reason why common life experiences such as poverty, stress, obesity or ageing are bad for public health.

Bullmore writes that the brain is rapidly emerging as one of the new frontiers for inflammation. He writes: “Doctors like myself, who went to medical school in the 20th century, were taught to think that there was an impermeable barrier between the brain and the immune system. In the 21st century, however, it has become clear that they are deeply interconnected and talk to each other all the time. Medical minds are now opening up to the idea that inflammation could be as widely and deeply implicated in brain and mind disorders as it is in bodily disorders.”

He asks: “Is that hope realistic for depression? It is beyond reasonable doubt that inflammation and depression are correlated with each other – or comorbid, to use some unlovable but important medical jargon. The key scientific questions are about causation, not correlation. Does inflammation cause depression? And, if so, how? One experiment that scientists have designed to tackle these questions is to do two functional MRI brain scans, one before and one after an inflammatory response has been deliberately provoked by the injection of typhoid vaccine. If there’s a difference in the two scans, that shows that bodily inflammation can cause changes in the way the brain works; if not, that would be a problem for the theory that inflammation can cause depression.

“A recent meta-analysis reviewed data from 14 independent versions of this experiment. On average, the data showed a robust effect of inflammation on brain activity. These results confirmed that bodily inflammation can cause changes in how the brain works. Encouragingly, they also localised the effect of inflammation to particular parts of the brain that were already known to be involved in depression and many other psychiatric disorders.”

Bullmore writes that if inflammation can cause depression then anti-inflammatory drugs should work as antidepressants. He says several studies have reviewed clinical trial data on thousands of patients treated with anti-inflammatory drugs for arthritis and other bodily disorders that are commonly associated with depressive symptoms. Overall, patients treated with anti-inflammatory drugs, rather than a placebo, had significantly improved mental health scores.

However, he writes, there is a caveat. The largest and most rigorous of these studies were designed to test drug effects on physical health and that makes it difficult to interpret the results too strongly as proof of beneficial effects on mental health.

He writes that the next step is to run studies designed from the outset to test new anti-inflammatory drugs as antidepressants, or to test existing antidepressants for anti-inflammatory effects.

“In doing so, we must avoid repeating one of our most habitual mistakes about depression, which is thinking that it’s all one thing, always with the same root cause. So, we shouldn’t be looking for the next “blockbuster” that can be automatically prescribed to make the whole world happier. We should be looking for ways to match the choice of treatment to the cause of psychiatric symptoms on a more personalised basis. And using blood tests to measure inflammation could help us to make those choices.”

Bullmore writes that currently, physical and mental health services are sharply segregated, reflecting a philosophical prejudice against viewing the mind and body as deeply intertwined. The links that many patients recognise in their own experience of illness tend to be somewhat discounted by the standard NHS provision of mental or physical healthcare services.

He says in contrast, the new science of inflammation and the brain is clearly aligned with arguments for breaking down these barriers in clinical practice. More than that, though, it has the potential to transform our thinking about illness more broadly. The barrier between mind and body, for so long a dogmatic conviction, appears to be crumbling.

[link url="https://www.theguardian.com/commentisfree/2020/jan/19/inflammation-depression-mind-body"]Full report in The Guardian[/link]

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