The Inflamed Mind: A Radical New Approach to Depression by psychiatrist Edward Bullmore presents inflammation as a new frontier in tackling depression. The author’s bio at the beginning of the book reveals that he works at pharmaceutical giant GlaxoSmithKline. He doesn’t try to be subtle about disclosing this, and I didn’t pick up any sense of bias. He explains that in 2010, GSK shut down its mental health R&D programs, which prompted him to start thinking seriously about neuro-immunology and the role of inflammation.
The author refers multiple times to his experience of social withdrawal and morbid rumination immediately following root canal surgery. It only lasted a day, but “you could say I had been a bit depressed”, likely due to post-surgical inflammation. I understand the point he was trying to make, but as someone with depression, I had to roll my eyes.
Cartoon drawings are effective at capturing neuro-immunology concepts. Explanations involve simple terms, without making the mistake of sacrificing accuracy for metaphor. Scientific terms are used, such as the immune cells known as macrophages, and the signalling molecules they release, called cytokines. While it’s somewhat difficult for me to judge, as I was familiar with many of these concepts, I think it was pitched to a level that a reasonably intelligent person could understand without having a science background.
A patient referred to as Mrs. P. makes frequent appearances throughout the book. The author encountered Mrs. P. during his medical training. She had rheumatoid arthritis as well as depressive symptoms; however, her treating physician insisted that the depression was a normal psychological reaction to arthritis. It was a relevant example, but it struck me as a bit over-used.
There was what seemed like a detour to philosopher René Descartes to explain the persistent idea of separation between mind and body. However, Descartes ended up appearing even more often than Mrs. P. did, to the point that it got to be a bit much. The author writes “I can fondly imagine that Descartes himself might have agreed with me, but I can’t be sure.” Oh my. He did make the interesting point, though, that the mind/body divide is a sort of “medical apartheid”, and I very much agree that a more holistic approach will better serve patients.
Bullmore argues that placing depression solely within the mental domain actually increases shame and the likelihood that people will think the illness is their fault, which is in many ways what the idea of a “chemical imbalance” tries to counteract. He goes on to explain the shortcomings of the serotonin hypothesis, which was the basis for the development of selective serotonin reuptake inhibitor (SSRI) antidepressants.
According to the author, approaching depression with a focus on serotonin and related neurotransmitters has stalled out, with no major advances in the treatment of depression since around 1990. He writes: “To this day, in 2018, I could still safely and acceptably treat most patients with mental health disorders based solely on what was written in those textbooks” that he used when he started his specialty training in 1989. While I understand the underlying point, that’s an unpalatable way to put it.
The book explains that according to the DSM: “According to the official diagnostic criteria of the American Psychiatric Association, depressed patients can only have a diagnosis of [major depressive disorder] if they do not also have a bodily disease.” Based on this, he concluded that Mrs. P. who had rheumatoid arthritis couldn’t have a depression diagnosis. To me this interpretation seemed a bit odd. The exact wording in the DSM-5 is: “The episode is not attributable to the physiological effects of a substance or another medical condition.”
Depression may have had an evolutionary role. The author explained that, back in the caveman days, social withdrawal could have been a form of quarantine to prevent infectious disease. He added that: “One might even wonder if the stigmatization of depression in 2018 is somehow related to the isolation of ancestral tribe members who were behaving as if they were inflamed.” That seems like a bit of a leap, and is followed by yet another leap: “Could the common feeling that ‘we don’t know what to say’ to our depressed friend conceal an ancient inherited instinct to recoil from close contact with people who are behaving as if they are inflamed and infectious?” By that argument, though, why isn’t there a social recoil from people with type I diabetes or Crohn’s disease? Or the oft-referred-to Mrs. P. with rheumatoid arthritis?
While there’s a strong argument that inflammation is a factor in depression, there isn’t much yet in practical terms. The book describes the “Remicade high” that some clinicians have seen in patients who rapidly cheered up while getting an infusion of that anti-inflammatory medication. There have been some small studies with anti-inflammatories that have had positive results, but there isn’t a clear indicator of something effective that’s available right now.
The book also identifies vagal nerve stimulation as a possible intervention to target inflammation. Cytokine receptors on the vagus nerve respond to high levels of inflammation by telling the spleen to deactivate macrophages to calm things down.
I started this book quite prepared to buy what the author was selling, given my prior knowledge on the topic. I was a bit surprised by the book’s presentation of the idea as though everyone is denying it, because it’s sufficiently accepted to have made its way into the mainstream continuing medical education talks I’ve seen. Bullmore writes that “we could be on the cusp of a revolution”, and my own hope is that advances in anti-inflammatory treatment approaches can help with my own depression.
The book makes a strong argument that further research into inflammation is going to open new doors in depression treatment. However, the fact that we don’t have keys to those doors yet limits its practical usefulness. Still, this book is worth reading if you want to learn more about this new way of looking at depression.
The Inflamed Mind is available on Amazon.
I received a reviewer copy of this book from the publisher via NetGalley.
You can find my other book reviews here.
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