The tics started when Jessica Huitson was just 12 years old. Over time, her condition worsened and she suffered attacks that affected her entire body for which she had to be taken to the emergency room. However, at the local hospital in Durham (England), they were blasé: they indicated that she suffered from anxiety and that she probably spent too much time watching videos on TikTok. Her mother describes the experience as “demeaning.” In reality, she Jessica suffered from an autoimmune disease caused by a strep bacterial infection. The pathology is known as pediatric autoimmune neuropsychiatric disorder associated with streptococcus (PANDAS). When the infection was identified and treated, the symptoms finally began to improve.
Huitson is not the only one to suffer from brain dysfunction confused with a mental disorder. There is increasing evidence that a series of infections can, in certain cases, trigger pathologies such as obsessive-compulsive disorder, tics, anxiety, depression and even psychosis. And infections are a small piece of the puzzle. It is increasingly clear that inflammatory disorders and metabolic conditions can also have measurable effects on mental health, although psychiatrists rarely look for them. All of this is symptomatic of the existence of major problems in psychiatry.
Better understanding could have profound consequences for the millions of people with mental illnesses who receive poor treatment today. For example, more than 90% of patients with bipolar disorder will have recurrent illnesses throughout their lives; and, in children with obsessive-compulsive disorder (OCD), more than 46% do not achieve remission. About 50-60% of patients with depression end up responding after trying many different drugs.
According to some professionals, a deeper understanding of the biology of mental health, related to clear biological fingerprints such as those that could be obtained in a laboratory test, will lead to more accurate diagnoses and better targeted treatments.
The field of psychiatry has historically focused on the description and classification of symptoms, rather than the underlying causes. The Diagnostic and Statistical Manual of Mental Disorders (DSM), sometimes called the Bible of psychiatry, emerged in 1952 and contains descriptions, symptoms, and diagnostic criteria. On the one hand, it has provided useful coherence to the diagnosis; but, on the other hand, it has grouped patients into cohorts without any criteria about the mechanisms underlying their conditions. There is so much overlap between the symptoms of depression and anxiety, for example, that some wonder if they are actually independent nosological categories. At the same time, depression and anxiety come in many distinct subtypes (panic disorder with or without agoraphobia, for example, are different diagnoses), but perhaps not all are significantly different. This can lead to patient groups in drug trials being so diverse that drugs and therapies fail simply because the cohort studied has too little in common.
Previous attempts to find causal mechanisms for mental health pathologies have encountered difficulties. In 2013, the National Institute of Mental Health, a US public agency, made a titanic bid to move away from research based on the DSM's symptom categories and poured money into basic research into brain disease processes in the hope of identifying a direct connection between genes and behaviors. New research was funded with some $20 billion, but the initiative ended in spectacular failure: most of the genes discovered had negligible effects. Allen Frances, a professor of psychiatry at Duke University, calls the search for such biomarkers “a fascinating intellectual adventure, but a complete clinical failure.”
It is clear that genes alone are not the answer. Ludger Tebartz van Elst, a professor of psychiatry and psychotherapy at Freiburg University Hospital in Germany, says many different disorders, such as schizophrenia, attention-deficit/hyperactivity disorder (ADHD), anxiety and autism, can be linked. triggered by the same genetic problem, 22q11.2 deletion syndrome, caused by the loss of a small fragment of chromosome 22.
Despite how little we still know, a potential change in psychiatry is on the horizon. In part, this is due to renewed interest in finding neurological biomarkers with increasingly sophisticated technology. Furthermore, it is now better understood that some mental pathologies actually have triggers or roots that should be treated as medical conditions and not psychiatric ones.
A key moment came in 2007, when work from the University of Pennsylvania showed that 100 patients with rapidly progressing psychiatric symptoms or cognitive declines actually suffered from an autoimmune disease. Their bodies created antibodies against key receptors on nerve cells known as NMDA receptors. These antibodies cause brain inflammation and can trigger a range of symptoms such as paranoia, hallucinations and aggression. The disease was named “anti-NMDA receptor encephalitis.” Most important of all, in many cases it was treatable by eliminating antibodies or using immunotherapy drugs or steroids. Studies of patients with first-episode psychosis have found that 5% to 10% also have antibodies that attack the brain.
It seems likely that, in rare cases, OCD may also be caused by the immune system. This is what is observed in the childhood condition PANDAS, diagnosed in Huitson in 2021. However, it also sometimes occurs in adults. A 64-year-old man reported spending an extraordinary amount of time obsessively mowing his lawn, behavior he recalled the next day with feelings of regret and guilt. The researchers discovered that these symptoms were caused by antibodies that attacked the neurons in his brain.
More recently, Belinda Lennox, head of psychiatry at the University of Oxford, has conducted tests on thousands of patients with psychosis. She has found elevated rates of antibodies in the blood samples of about 6% of patients, mostly directed against NMDA receptors. She notes that it remains unknown how a single set of antibodies is capable of producing clinical pictures ranging from seizures to psychosis and encephalitis. It is also not known why these antibodies are produced, nor if they can cross the blood-brain barrier, a membrane that controls access to the brain. In any case, Dr. Lennox assumes that they do, preferentially adhering to the hippocampus, which would explain why they affect memory and cause delusions and hallucinations.
Lennox states that a change in medical thinking is necessary to assess the damage that the immune system is capable of causing to the brain. The “million-dollar question,” she maintains, is whether such conditions are treatable. She is currently carrying out trials to find out more. Work in patients with immune-mediated psychosis suggests that a series of strategies, such as the elimination of antibodies and the administration of immunotherapy drugs or steroids, can lead to effective treatments.
Another important discovery is that metabolic alterations can also affect mental health. The brain is an energy-consuming organ, and metabolic alterations related to energy pathways have been implicated in a diverse range of conditions, including schizophrenia, bipolar disorder, psychosis, eating disorders, and major depressive disorder. At Stanford University there is a metabolic psychiatry clinic where patients are treated with diet and lifestyle changes, as well as medication. An active field of research in the clinic is the potential benefits of the ketogenic diet, in which carbohydrate intake is limited. Such a diet forces the body to burn fat for energy, which creates chemicals known as ketones that can act as a fuel source for the brain when glucose is low.
Kirk Nylen, head of neuroscience at Baszucki Group, a US charity that funds brain research, says 13 trials are underway around the world studying the effects of metabolic therapies on serious mental illness. Preliminary results have shown a “large group of people responding in an astonishingly significant way. "These are people in whom drugs, psychotherapy, transcranial stimulation and perhaps also electroconvulsive therapy have failed." As he claims, he continually meets psychiatrists who have moved into the metabolic field because of the enormous improvements in mood experienced by patients on low-carbohydrate diets. Results from randomized controlled trials are expected within the next year or so.
And what improves is not just the understanding of the immune and metabolic systems. Huge amounts of data are now being analyzed at unprecedented speed, sometimes with the help of artificial intelligence, to uncover connections that were previously hidden in plain sight.
All of this could finally place biology in a more central place in the diagnosis of mental health, which would translate into more individualized and effective treatments. In early October 2023, UK Biobank, a British biomedical database, published data revealing that people with depressive episodes had much higher blood levels of inflammatory proteins, such as cytokines. Another study last year found that about a quarter of depressed patients had evidence of low-grade inflammation. This information could be useful, since other research indicates that patients with inflammation respond poorly to antidepressants.
There are more innovations underway. Some researchers are exploring different ways to improve the diagnosis of ADHD, for example by classifying patients into a number of different subgroups, some of which would not have been considered until now. In three separate announcements made in February 2024, different groups announced the discovery of biomarkers that could predict the risks of dementia, autism, and psychosis. The search for better diagnostic tools is also likely to be accelerated by the use of artificial intelligence. The company Cognoa is already using it to diagnose autism in children by analyzing recordings of their behavior, thereby avoiding long waits for clinical specialists. Another research team, at the University of California's Quantitative Biosciences Institute (QBI), has used it to create an entirely new map of the protein-protein interactions (and molecular networks) involved in autism. That will greatly facilitate future explorations of diagnostic tools and treatments.
All of these advances are promising. However, it would be possible to solve many of the field's problems by relaxing the distinctions 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 mental disorders. of behavior. Lennox finds it extraordinary that treatment options differ so much depending on whether a patient ends up in a neurology ward or a psychiatric ward. He wants to make antibody testing more routine in Britain when someone presents with a sudden post-viral mental illness that does not improve with conventional treatments. Thomas Pollak, professor and consultant neuropsychiatrist at King's College London, says that MRI should probably be used in patients after a first episode of psychosis since, in 5% to 6% of cases, it would change the way they are treated.
This gap between neurology and psychiatry is greater in the Anglo-Saxon countries, says Dr. Tebartz van Elst. (That is, in countries such as the United States, Great Britain, Canada, and New Zealand.) In Germany, psychiatry and neurology are more integrated; Neurologists train in psychiatry, and psychiatrists do a year of neurology as part of their training. This makes research work easier. Tebartz van Elst says that he offers most patients with first-episode psychosis or other severe psychiatric syndromes an MRI of the brain, an electroencephalogram, laboratory tests to detect inflammation, and a lumbar puncture to find evidence to support different treatments. in some patients. The price, about 1,000 euros, does not exceed the cost of hospitalizing a patient for three or four days, he says, so the quality-price ratio is not bad.
All this work will one day put psychiatry, and its patients, on a firmer footing. It is already beginning to offer validation for some patients for whom discipline has failed.
Jessica Huitson is just one case. Diagnosed and treated too late, she continues to struggle with her pathology and her future is uncertain. Those who suffer from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a post-infectious disease that is accompanied by a series of cognitive problems such as attention and concentration deficits, were previously considered malingerers or diagnosed with “yuppie flu.” New research indicates that it is associated with both immunological and metabolic dysfunction.
Some wonder if these conditions are the tip of a much larger iceberg. The reward for finding out more will be better patient care and better outcomes. Biology is coming, whether psychiatry is ready or not.
© 2024 The Economist Newspaper Limited. All rights reserved
Translation: Juan Gabriel López Guix
