[ad_1]
Ms Hutson is not the only one who has had a problem with mistaking disorders in the brain for disorders in the mind. There is growing evidence that a range of infections can, in some cases, trigger conditions such as obsessive-compulsive disorder, tics, anxiety, depression and even psychosis. And infections are just a small part of the puzzle. It is becoming increasingly clear that inflammatory disorders and metabolic conditions can also have a big impact on mental health, although psychiatrists rarely pay attention to them. All of this is symptomatic of bigger problems in psychiatry.
The revised understanding could have serious consequences for millions of people with mental health conditions that are currently poorly treated. For example, more than 90% of patients with bipolar disorder will have recurrent illness in their lifetime; and more than 46% of children with obsessive-compulsive disorder (OCD) do not achieve remission. About 50-60% of patients with depression eventually recover after trying several different medications.
For some in the profession, a deeper understanding of the biology of mental health, coupled with a clear biological fingerprint obtained from laboratory testing, would lead to more accurate diagnoses and better targeted treatments.
Shrink Wrapped
The field of psychiatry has historically been centered around the description and classification of symptoms rather than underlying causes. The Diagnostic and Statistical Manual of Mental Disorders (DSM), sometimes known as the bible of psychiatry, came out in 1952 and includes descriptions, symptoms, and diagnostic criteria. On the one hand, this has brought helpful consistency to diagnosis. But on the other, it has grouped patients into clusters without any understanding of the underlying mechanisms behind their conditions. For example, there is so much overlap between the symptoms of depression and anxiety that some people wonder if these are actually separate categories of illness. Also, depression and anxiety come in many different subtypes – panic disorder with and without agoraphobia, for example, are separate diagnoses – not all of which can be meaningfully distinguished. This can lead to patient groups in drug trials being so diverse that medications and treatments fail simply because there is little similarity in the group being studied.
Previous attempts to find causal mechanisms for mental health conditions have been difficult. In 2013, the National Institute of Mental Health, a US government agency, took a heroic gamble of moving away from research based on the symptom-based categories of the DSM. Money was poured into basic research on the brain’s disease processes, hoping to link genes directly to behaviour. Nearly $20 billion of new research was funded, but the idea failed miserably – most of the genes discovered had little effect. Allen Frances, a professor of psychiatry at Duke University, calls the search for such biomarkers “a fascinating intellectual adventure, but a complete clinical failure”.
Genes alone are clearly not the answer. Many different conditions such as schizophrenia, attention deficit hyperactivity disorder (ADHD), anxiety and autism may start with the same genetic disorder, 22q11.2, which is caused by the loss of a small piece of chromosome 22, says Ludger Tebartz van Elst, professor of psychiatry and psychotherapy at University Hospital Freiburg in Germany.
Despite this sad adversity, change in psychiatry is potentially on the horizon. Part of it is coming from a revived interest in finding neurological biomarkers with more and more sophisticated technology. Also, there is a greater understanding that some mental-health conditions actually have triggers or roots that should be treated as medical conditions rather than psychological conditions.
Fundamental Health
A key moment came in 2007, when work done at the University of Pennsylvania showed that 1 in 100 patients with rapidly progressing psychotic symptoms or cognitive impairments actually had an autoimmune disease. Their bodies were making antibodies against key receptors in nerve cells known as NMDA receptors. These cause inflammation of the brain and can trigger a variety of symptoms, including paranoia, hallucinations and aggression. The disease was named “anti-NMDA-receptor encephalitis”. Most importantly, it could be treated in many cases by removing the antibodies or using immunotherapy drugs or steroids. Studies of patients with a first episode of psychosis have found that between 5% and 10% also have antibodies that attack the brain.
It seems that, in rare cases, OCD can also be caused by the immune system. This is seen in the childhood condition PANDAS, which Ms Hutson was diagnosed with in 2021. But it is also sometimes found in adults. A 64-year-old man reported that he would spend an extraordinary amount of time obsessively trimming his lawn, but would look back on this behaviour the next day with feelings of regret and guilt. Researchers found that these symptoms were being caused by antibodies attacking neurons in his brain.
Recently, Belinda Lennox, head of psychiatry at the University of Oxford, has carried out tests on thousands of patients with psychosis. She has found an increased rate of antibodies in the blood samples of about 6% of patients, mostly targeting NMDA receptors. She says it is still unknown how a set of antibodies can cause clinical presentations ranging from seizures to psychosis and encephalitis. Nor is it known why these antibodies are formed, or whether they can cross the blood-brain barrier, a membrane that controls access to the brain. However, she believes they do – preferentially sticking to the hippocampus, which would explain how they affect memory and lead to delusions and hallucinations.
Dr. Lennox says a shift in medical thinking is needed to understand the damage the immune system can do to the brain. She says the “million-dollar question” is whether these conditions are treatable. She is now conducting trials to find out more. Research on patients with immune-driven psychosis suggests that several strategies, including removing antibodies and taking immunotherapy drugs or steroids, may be effective treatments.
Another important finding is that metabolic disturbances can also affect mental health. The brain is an energy-hungry organ, and metabolic changes related to energy pathways have been implicated in a variety of conditions, including schizophrenia, bipolar disorder, psychosis, eating disorders, and major depressive disorder. Stanford University has a metabolic psychiatry clinic where patients are treated with diet and lifestyle changes as well as medication. An active area of research at the clinic is the potential benefits of the ketogenic diet, in which carbohydrate intake is limited. This diet forces the body to burn fat for energy, creating chemicals called ketones that can act as a fuel source for the brain when glucose is in limited supply.
Kirk Neylan, head of neuroscience at the Baszucki Group, an American charity that funds brain research, says there are 13 trials underway worldwide to look at the effects of metabolic treatments on serious mental illness. Early results have shown that “a large group of people are responding in an incredibly meaningful way. These are people who have failed medications, talk therapy, trans-cranial stimulation and perhaps electroconvulsive-shock therapy.” He says he keeps meeting psychiatrists who have come into the metabolic field because of patients who have had huge improvements in mood after low-carb diets. Results of the randomised controlled trials are expected within the next year or so.
It’s not just the understanding of the immune and metabolic systems that’s improving. Huge amounts of data are now being parsed at unprecedented speeds, sometimes with the help of artificial intelligence (AI), to uncover previously hidden connections.
Dr. Jung, tear down this wall
This could lead to biology becoming more central to mental health diagnoses, potentially leading to more personalised treatments as well as better therapies. In early October 2023, the UK Biobank, a biomedical database, published data that showed that people with depressive episodes had significantly higher levels of inflammatory proteins such as cytokines in their blood. A study last year also found that about a quarter of depressed patients had evidence of low-level inflammation. This could be useful to know as other research suggests that patients with inflammation respond poorly to antidepressants.
There are further innovations taking place. Many researchers are exploring different ways to improve the diagnosis of ADHD, for example, classifying patients into several different subgroups, some of which may have been previously unknown. In three separate announcements in February 2024, different groups announced the discovery of biomarkers that can predict risks of dementia, autism and psychosis. The search for better diagnostic tools is also likely to be accelerated by the use of AI. One firm, Cognoa, is already using AI to diagnose autism in children by analysing footage of their behaviour – avoiding long waits for clinicians. Another organisation, the Quantitative Biosciences Institute (QBI) in California, has used AI to create an entirely new map of the protein-protein interactions (and molecular networks) involved in autism. This will greatly facilitate further explorations of diagnostic tools and treatments.
All such developments are promising. But many of the field’s problems could be solved by reducing the differences that exist today between neurology, which studies and treats physical, structural and functional disorders of the brain, and psychiatry, which deals with mental, emotional and behavioural disorders. Dr Lennox finds it extraordinary that treatment options differ so much whether a patient goes to a neurology ward or a psychiatric ward. She wants antibody testing to be more routine in the UK when someone comes in with a sudden post-viral psychotic illness that does not respond to standard treatments. Thomas Pollack, a senior clinical lecturer and consultant neuropsychiatrist at King’s College London, says MRI scans should probably be used on patients after their first episode of psychosis because in 5% to 6% of patients, it would change the way they are treated.
Dr. Tebartz van Elst says this rift between neurology and psychiatry is greater in Anglo-Saxon countries. (These countries include the US, UK, Canada and New Zealand.) Psychiatry and neurology are more integrated in Germany, where neurologists train in psychiatry, and psychiatrists do a year of neurology as part of their training. This makes it easier to do diagnostic work. He says he offers most patients with first-time psychosis or other severe psychiatric syndromes an MRI of the brain, an electroencephalogram, lab tests for inflammation and, in some patients, a lumbar puncture to find evidence to support different treatments. It costs about €1,000 ($1,070), not much more than the cost of hospitalizing a patient for three or four days, says Dr. Tebartz van Elst.
What is its diagnosis?
All of this work will one day put psychiatry and its patients on a stronger footing. It is already providing recognition to those the field has failed.
Jessica Hutson is just one of them. Having been diagnosed and treated too late, she is still struggling with her illness and her future is uncertain. People with ME/CFS, a post-infection condition that comes with a range of cognitive problems such as lack of attention and concentration, were once dismissed as a façade of illness or diagnosed as “yuppie flu”. New research suggests it is linked to both immune and metabolic dysfunction.
Some wonder if these conditions are just the tip of a very large iceberg. The reward for knowing more will be better patient care and outcomes. Biology is coming, whether psychiatry is ready or not.
© 2024, The Economist Newspaper Limited. All rights reserved. From The Economist, published under licence. Original content can be found at www.economist.com.
[ad_2]
