Some years ago Camilla Nord suffered such persistent pain at the site of an old injury that doctors thought she would need major surgery – a joint replacement in her foot. To delay this for a few months, they injected the foot with steroids. Steroids wear off – but nearly a decade later, the pain was still much reduced. To Nord, whose day job is running the Mental Health Neuroscience Lab at the University of Cambridge, this was fascinating. Not all of her pain, it seemed, came from her foot.
As Nord knew, chronic pain can cause physiological changes in the brain – a process that is now measurable in the lab. It seemed to her that her brain, as she puts it in her recent book, The Balanced Brain, “had become used to pain, monitored pain, and had begun to enhance the sensation of pain on my body”. Removing the original source of the pain for a few months had altered this process of neuroplasticity enough to make a lasting difference to the amount of pain she experienced, even after the trigger in her foot returned.
A conceptual division between mind and body has underpinned western culture, and medicine, for centuries. Illnesses are “physical”, or they are “mental”. But, Nord writes, there is no “separate category of illness, one that is confined to the mind and does not involve biological changes. This category does not exist.” Not only that, she says, but the reverse also applies: there is no purely “physical” ailment in which your brain does not play a role. Recent research makes it increasingly possible to demonstrate this; it also has profound implications for the way all illness should be approached.
Nord has been amused, in the months since her book was published, by how these assertions have been received – including many variations on, well, duh. “People say, ‘Well, obviously the body is involved in mental health – what do you mean you guys are just now discovering this?’” But it is one thing to understand that food poisoning might come along with misery, for instance, or anxiety with higher heart rate and perspiration, and quite another to accept the science that shows, as she puts it, that “everything is physical and psychological”. As Monty Lyman argues in his eye-opening tour of recent advances in immunology, The Immune Mind, it is nothing less than a revolution.
This revolution could be transformative for the millions of people for whom, as Lyman puts it, misguided dualistic approaches “are causing … preventable and relievable harm”. Currently, “physical” and “mental” medical services often have different budgets and administrations. They may occupy different buildings, and may not share notes. The medical system often consists of discrete transactions – short visits to GPs, specialists and subspecialists – and the division of illness into specific, containable issues, resulting in a pill, an operation or a course of treatment. It’s a top-down arrangement that tends to treat a passive patient as a set of individual parts that require attention.
Furthermore, the “physical” is frequently prioritised over the “mental” in terms of budgets and attention. It can be more difficult, for example, to access NHS funds for someone with severe dementia whose “body” is still healthy than for someone experiencing the opposite. People with major mental health disorders (such as schizophrenia, bipolar disorder, major depression) often die years earlier – up to a decade or even two earlier – than those who do not. “People often think, ‘Well, that’s because they’re committing suicide,’” says Mark Edwards, a professor of neurology at King’s College London. In fact, “they’re dying of cancer, heart disease, complications of diabetes and respiratory problems”, in part because they are not able to access adequate physical care (they may also be unable to comply). Even if they do access treatment, they are often treated differently enough – in cancer services, for instance – to have measurably worse outcomes.
And then there are the further millions whose troubles fall between categories. Nord uses the example of functional neurological disorder (FND), “the most common medical condition you’ve never heard of”. Patients with FND may have symptoms ranging from seizures, paralysis or brain fog to irritable bowel syndrome or urinary issues; from complex and shifting patterns of pain to tinnitus and movement and sensory disorders, and they account for up to a third, sometimes more, of those attending outpatient neurology clinics. FND is the second most common reason to see a neurologist, after headache. The symptoms affect people’s functioning – hence the name – but they are, crucially, symptoms for which no corresponding structural damage can be found. The resulting levels of disability, adverse effects on quality of life and costs to the healthcare system, notes Nord, are “comparable with those seen in conditions such as epilepsy or multiple sclerosis”. Tiago Teodoro, a consultant neurologist who recently organised a symposium on functional disorders at St George’s Hospital in London, says, “Disabling FND is as frequent as Parkinson’s.”
People with FND may be further disabled because they are systematically not believed. “People say pejorative things,” says Nord. “They say: ‘It’s all in your mind.’ And that’s a really sad example of how this kind of societal model can really let patients down.” The inference that FND is somehow faked, or malingering, has been shown to be untrue. Nord, whose ability to make research come alive is matched by a kind of thrilling intensity, also tells me about a “lovely neuroimaging paper” that “shows that people faking symptoms look totally different in the brain [scans] than [those with] functional symptoms … It’s distinct from something that you have agency over.” Faking or malingering, says Simon Wessely, a consultant psychiatrist at King’s College London who specialises in the overlap between mental and physical health, is “unbelievably rare”. But the spectre of it can haunt patient-doctor interactions, and “it’s a great pity. Because it really gets in the way of actually getting better.”
Edwards, who has spent 15 years researching, treating and advocating for people with FND, places the problem at the nexus of “body” and “mind”. “It’s the system of consciousness, effectively. Consciousness is not a passive thing. It allows introspection and thinking and then directs the body to do something. One of the things that really sets human beings apart from other animals is how amazingly developed this system is. In FND, that system goes wrong. People are out of contact with their body. All of the basic wiring is OK, but they can’t get their body to do what they want it to. They can’t get it to move, or they’re having episodes where it’s moving on its own, like a seizure, or they’re not getting normal feedback from their bodies, or they feel numb, or they feel weird sensations. And that can extend to other symptoms that people might experience – for example, pain or problems with thinking or memory.”
It is striking, Edwards adds, how often there is a specific trigger. “Something like having an accident, an operation, a bad flu, a migraine, a drug reaction. Often something happening to the body.” Acute stress can do the same, but episodes can also be quite mild. “And that seems, in some people, to be capable of causing this system to malfunction, sometimes quite significantly.”
Functional issues, he argues, are often part of illnesses such as fibromyalgia, some kinds of chronic pain and multiple chemical sensitivity – but they are also implicated in supposedly “straightforward” physical illnesses such as heart disease or respiratory ailments. Mapping the measurable state of the muscle that is the heart, for instance, on to the symptoms the patient is experiencing often shows a poor correlation. This gap, Edwards says, is where the rest of the person is: their system of consciousness, plus “their emotional and mental health, psychosocial factors – environment, support and so on – and many other things. [It is] a huge untapped source of possible improvement in symptoms for people who are ill, and by ignoring it in research and clinical practice we are directly making people more sick than they need to be.”
Nord also highlights the danger to scientific research. A separation of “mind” and “body” carries “really profound risks, [not only] with the way we think about what a disorder is, but also how we might go about designing new treatments” – or, in fact, whether we can comprehend how the treatments we currently use actually work.
One way in which this is beginning to change is through an understanding of the brain as a place of predictive processing. In other words, it has a general picture, or story, of what it expects to see, which is then adjusted according to the sensory information received from both outside and inside the body; a process – again, measurable in terms of neurons firing – of connections made or pared away. It is important to remember, however, that, as Lyman puts it, “your brain is less focused on reality than it is on meaning”.
Many illnesses, in this model, arise from maladaptive – or even over-efficient – processing. So, for instance, an injury that the brain has had to respond to in the past makes it more sensitive to a repeat of that injury in the future. This, writes Nord, can “cause your brain to unconsciously predict physical symptoms”, and rush to defend against them. “Sometimes these predictions might be so strong that they generate the symptoms they anticipate.” An extraordinary 1970 experiment found that rats that had been given sugar water laced with toxins fell ill even after the toxins were removed; they had become so good at connecting sugar water to illness that some even died. We are not rats, of course, but the principle is the same: we can become conditioned to expect negative outcomes, and those expectations can make us ill.
Wessely reminds me about Pavlov’s dogs. “You have the unconditioned stimulus – food makes them salivate automatically, but if you ring a bell at the same time, it doesn’t take long before they salivate just with the bell and not the food. That’s the conditioned stimulus.” Something similar can happen in humans, he argues, and underlies many disorders, such as agoraphobia, social phobia, specific phobias to spiders or dogs, or the phenomenon of electromagnetic hypersensitivity. Perhaps someone is taken sick, or faints, and by coincidence is in a crowded supermarket. “But then the same thing happens every time they go back to the supermarket. The symptoms they develop are extremely real, highly physiological, but now have a different explanation, the surge of adrenalin caused by fear.” Such conditioned responses can be further amplified by prior beliefs, for example about risk – a process called a “nocebo” effect. If one definition of a placebo might be the powerful therapeutic use of pure expectation, a nocebo is its evil twin.
And prediction is, of course, the model we use to understand the functioning of the immune system: identification of a threat, followed by the dispatch of cells specifically adapted to neutralise that threat – ie, inflammation. We usually assume such threats to be “physical” as opposed to “mental” – bacteria, or a virus – but it is increasingly clear, says Lyman, that the immune system does not differentiate: the threat could just as easily be emotional distress, environmental challenges, childhood trauma or “even being sedentary”. The resulting inflammation does not differentiate either.
Not long ago, Lyman submitted to two experiments in which he was injected with bacterial toxins. In the first, within 24 hours, his mood had dropped. He felt fatigued, did not want to socialise and could not concentrate or feel pleasure. In the second, such feelings were joined by a marked turning-inward, which he describes as: “A mindfulness body-scan from hell, focusing on what I thought was going wrong with my body and health … I paid far more attention to the state of my body – particularly negative, uncomfortable states – than I would usually.”
We recognise this as basic illness behaviour, familiar from, for example, the common cold. And, short term, it’s useful: the body forces us to stay home, heal and not go out spreading germs. We may not think, however, about how closely all these symptoms overlap with the symptoms of depression. So closely, in fact, you could say that the injection had effectively caused a 24-hour depression.
“Inflammation nudges us towards being more sensitive to negative information,” Neil Harrison, the Cardiff immunopsychiatrist who ran the second experiment, told Lyman, after he had recovered. “For some, this can push them into a downward spiral.” Why do some fall and not others? It is crucial to note, Lyman says, “that it isn’t someone’s fault for falling”. It is possible, Lyman continues, that “inflammation itself could interfere with the brain’s updating of predictions about inflammation”. The brain, in effect, gets stuck, fighting an infection that is no longer there.
There are two significant points here, in terms of what we can do about it. The first is that if inflammation can cause what we recognise as depression (alongside many other drivers, such as stress or trauma, or genetic factors), there is a significant number of people for whom the current standard treatments – SSRIs, talk therapy – do not make sense. The second arises from the idea of being stuck: stuck in a pattern of reaction to pain, mental threat, trauma or stress. And, given the way the brain works, being stuck, and reacting over and over in the same way, only exacerbates the problem: the brain gets better and better at producing that reaction.
But stuckness also gives a clue to possible treatments. If “the specific way that your brain changes depends on what you were expecting to happen”, Nord writes, it follows that anything that dislodges that expectation, even a little, can make space for other, more positive expectations to creep in – and these, in turn, can be fortified by repetition. For about 50% of people, for instance – far fewer than is generally assumed – SSRIs can work in this way. Others might respond to transcranial magnetic stimulation, which can be effective in depression, OCD and smoking cessation. Talk therapy also works like this, and in a wider range of situations than one might think: irritable bowel syndrome, for example, which causes indisputably physical effects such as stomach cramps, bloating, diarrhoea and constipation, has been shown in some studies to improve with CBT.
Another new frontier is research into interoception, or the mechanisms by which we all track our internal information. As humans we put great store in this kind of self-knowledge – “Go with your gut”; “I feel what I feel” – in these cliches our interior worlds are a source of undeniable truth. But it is now possible to measure some surprising gaps between what we think is happening within us (and therefore the information to which our brains react), and what is actually going on. And, baldly put, we are often not very good at it.
People with anxiety and depression are especially challenged in this regard. As Lyman discovered, feeling depressed makes us focus inward; this often results in an over-reading of what we find there. Depression, says Sarah Garfinkel, a cognitive neuroscientist at UCL, is also associated with “a reduction of interoceptive accuracy” – again, a drop that can actually be measured in the lab. “So it’s over-reading in the presence of poor precision.”
Rather than being discouraging, this is good information to work with, argues Garfinkel, who with Chatrin Suksasilp, Hugo Critchley and others has just completed clinical trials in which, over a six-week period, they trained individuals suffering from anxiety to get better at listening to their own heart-rates. In a third of those individuals, anxiety not only dropped markedly, but stayed lowered for a full year, a result about which Garfinkel sounds giddily excited. “With drugs, you know, you’re then dependent on the drug,” she says – and talking therapies or CBT can be hard to implement in those most anxious or depressed, as well as taking a long time and being costly. But if these results, which are awaiting peer review, stand up, “this is a behavioural technique you can take forward for the rest of your life”.
What all of these possibilities have in common is that they harness the whole human – and a belief in our ability (and especially in the ability of our brains) to change. The brain is wiring and rewiring itself all the time, Nord reminds me; this is “a constant of your life”. There’s an optimism, also, “in the breadth of treatments that exist”, and that while there is no magic bullet, “just because something hasn’t worked for someone else, or just because a treatment hasn’t worked for you before, the nuances of how a treatment interacts with your brain as an individual at that moment means it may well work for you at a different time”. Or it may work in combination with something else.
This all requires a fundamental willingness from everyone – including the patient – to avoid what Lyman calls the “two fallacies. The first is of ‘mind over matter’ – believing that [illness] can instantly be cured by a positive outlook. The second is a reductionist ‘matter over mind’ approach: all feelings and symptoms must be an accurate reflection of what is going on in the body.” As Nord puts it, the “belief that physical symptoms only come from the body becomes a barrier for you to be treated effectively, and recover”.
But holistic treatment is not easy to find. Teodoro’s FND symposium gathered professionals from across the medical spectrum – neurology, urology, gastroenterology, psychiatry, psychology, physiotherapy. As far as he knows, no such symposium, focused on treatment, has happened before. Which is a pity, he says, because FND “is a treatable condition”.
All argue that there is an urgent need to break down centuries’ worth of institutional and cultural barriers and use all available methods – cognitive, emotional, social and physical. “Somehow,” says Edwards, “in the biomedical revolution, which has been fantastically effective and beneficial in so many ways, this bit has got lost and sidelined into something which feels less real, unimportant and fundamentally stigmatised as a person’s fault and sole responsibility. This is what people need to know: there is such a massive prize here, if only we can have an honest, adult conversation about the full range of things that drive illness, and then take appropriate action to make it better.”
Article by:Source: Aida Edemariam
