On an average NHS ward, one in three people is depressed (providing you don’t count the doctors and nurses). The great majority of these patients are not there for depression. It’s most likely that they’re elderly with a long ‘problem list’, and psychiatric conditions will be
near the bottom. Hopefully there’s been an attempt to treat their low mood, starting with an SSRI (selective serotonin reuptake inhibitor) antidepressant. It is probably working a bit. To hear a patient wheeze with every breath, seeing their contorted joints or smelling their suppurating wounds, it’s easy to think, in their condition, who wouldn’t feel depressed?
Through the centuries, depression has been understood as black bile in the blood, moral failure, psychic strife, and a chemical imbalance of neurotransmitters. But no clear mechanism for how and why depression occurs has ever been proved. Pharmaceutical companies are withdrawing from research into new psychiatric medications, due to spiralling costs and low return. Prozac was the last breakthrough. That was over thirty years ago. With depression, a stubbornly stigmatised disease, set to become the largest cause of disability worldwide by 2030, a new paradigm is overdue.
Edward Bullmore, head of psychiatry at the University of Cambridge, is fed up with modern medicine’s indebtedness to Descartes: mind on one side, body on the other. He argues that physical health conditions are not only indirectly linked to depression by pain, fear and isolation. There is a more intimate, physiological connection. An inflammatory disease – whether infective, autoimmune, cancerous or degenerative – can lead to inflammation in the brain. Even a passing reaction to flu can make you blue for the same reason. Moreover, patients with depression often have raised inflammatory markers in their blood.
Bullmore is not saying that depression is physical rather than mental. He challenges the division altogether. Your immune system’s billion or so white blood cells produce cytokines and antibodies in response to invasion or damage. Somewhat heretically, Bullmore argues that these chemical messengers can cross the ‘blood brain barrier’, which was traditionally thought to protect your grey matter. His theory contradicts what he – and I, a graduate of 2018 – were taught in medical school. We are still Cartesians now.
Not everyone with depression is inflamed; and not everyone who is inflamed will be depressed. But Bullmore, himself a part-time employee of Glaxosmithkline, reckons about a third of patients with major depressive disorder will one day be identifiable via a blood test at their GP surgery, and will benefit from anti-inflammatory drugs. These future medications could be twice as effective as SSRIS, he predicts. However, ‘the mechanistic narrative is not yet crystal clear’ in terms of causation and placebo effect.
If Bullmore is right, why does it matter? Inflammation is as voguish as the microbiome, and has been implicated in almost all diseases. But that’s the power of his book. Depression could – at least in part – be much more like other diseases than previously thought. As with rheumatoid arthritis or multiple sclerosis, say, personal culpability is irrelevant. Like cancer, depression can happen to anyone, and may take many forms with various causes, some genetic (44 genes have been implicated so far), some environmental; often both.
The Inflamed Mind is radical in its optimism and also its inclusivity. Bullmore makes space for the fact that many patients do benefit from SSRIS, and that depression has social as well as biochemical determinants. Patients with poor mental health are more likely to be experiencing stress, discrimination and a lower standard of living, all of which have been shown to increase bodily inflammation. In turn, psychotherapy, mindfulness, lifestyle changes and sunshine may play a role in its treatment.
I don’t suppose it will be the public who are most resistant to this book. Bullmore encourages scepticism but is disappointed by some colleagues’ reflex sneering at the mention of immunopsychiatry. It will take ‘a new breed of doctors’ to follow this research through, he says: rheumatologists who routinely ask about mood, and psychiatrists who are willing to dust off their stethoscopes. It may be the professionals, not their patients, who need to pull themselves together.