Blood test to diagnose bipolar disorder - skepticism among researchers remains
Blood test to diagnose bipolar disorder - skepticism among researchers remains
A new blood test that uses organic markers to distinguish bipolar disorders from depression could shorten the time that is required for a precise diagnosis from years to weeks, according to the company that has developed the test. However, some scientists express concerns about the validity of the test.
The test uses biomarker that are related to RNA processing to diagnose the disease and has been available in France since March and since October 2023 in Italy after receiving the official approval in both countries.
However, some researchers are concerned about the small number of subjects in the studies on which the test is based, as well as the lack of independent reviews of these studies. The developers of the test, the French start-up Alcediag based in Montpellier, claim that their studies are valid and reproducible.
This dispute raises a broader discussion about the potential of biomarkers - biological characteristics that can indicate a certain state of health - to enable previous diagnoses and personalized treatments for psychiatric disorders. "There is a role in researching biomarkers," says Suresh Sundram, psychiatrist at Monash University in Melbourne, Australia. "But this is a very sensitive area."
slow diagnoses
bipolar disorders, a spectrum of diseases characterized by mood swings between mania and depression are difficult to diagnose. Around 40 million people live with this disease worldwide, and the diagnostic process, which often includes several sessions with a psychiatrist, takes an average of seven to ten years. During this time, many patients are incorrectly with diseases such as Depression diagnosed and preserved inappropriate or ineffective treatments.
Alcediag hopes to change this dark picture. The company claims that its blood test EDIT-B, which costs 900 euros ($ 980), can help distinguish bipolar disorders from depression by using biomarkers. Edit-B differentiates between the two diseases by subtle differences in the RNA processing measures-a regulatory process that changes various cellular mechanisms, including gene expression, which in turn influences neurological function.
Several studies have proposed that differences in RNA processing could play a role in autoimmune diseases, cancer and psychiatric diseases. In initial research, scientists from Alcediag Distincte RNA processing patterns, which affect eight genes, seem to vary between healthy people and those with depression. Among the depressed patients, six of these genes also show variations that distinguish people with depression from those with bipolar disorder. These differences lead to a unique combination-or signature-of biomarkers that the company has discovered using an artificial intelligence algorithm developed by it.
"We have a signature for depressive people, a signature for the controls and one for bipolar disorders," says Dinah Weissmann, co -founder and scientific director of Alcediag. In a study from 2022 with 410 participants, the algorithm was able to distinguish the 160 people with depression and the 95 people with bipolar disorder with high accuracy 1 .
About 80 people have used the test since EDIT-B's commercialization in France and Italy, says Weissmann, and the feedback has so far been positive. She quotes the anecdotal report of a person who reported after receiving a positive test result that it was switched to more effective medication. "The patient wrote to his doctor: 'It's great, I'm on my feet again. I live normally," says Weissmann.
potential risks
For many people with bipolar disorder, a faster, more precise diagnosis would enable them to get “the right medication at the right time”, says Marion Leboyer, psychiatrist and managing director of the Fondamental Foundation, a research organization at Paris.
On the other hand, there is the possibility that disruptions will be diagnosed or overlooked incorrectly in the event of a faulty blood test, warns Boris Chaumette, psychiatrist at the French National Institute for Health and Medical Research in Paris. So far there are no signs that a result from EDIT-B has led to an incorrect diagnosis. However, chaumettes and others express concerns about the methods of certain studies used to demonstrate the effectiveness of the EDIT-B test. He indicates the "inherent boundaries" of the 2022 study with 410 participants. "You have a data record with many variables and not many patients, and you ask an algorithm to classify people. It will inevitably find things that classify them and he will inevitably recognize similarities," he says. "In reality, what you observe could reflect the effect of treatments."chaumet adds that apart from the control group, every person who took part in Alcediag's studies took medication (which is often the case with psychiatric research). These drugs could influence the values of some biomarkers, says Sundram, "so the algorithm could capture the effect of the drug".
Weissmann explains that the study participants with bipolar disorder and those with depression take a variety of different medications. If the algorithm had differentiated people based on their treatments, he would have classified them according to therapeutic classes. Even stable patients-those with a diagnosis, but who had no symptoms at the time of the study-had a different biomarker signature than the control group, which indicates that their medication suppressed the symptoms without influencing the markers of the underlying disease. She says that Alcediag's studies included hundreds of participants and that the company conducts a new clinical study with 436 patients; The results are expected for the next year.
Questions about reproducibility
Some aspects of Alcediag's studies make it difficult for independent researchers to check the work, says Chaumette. The algorithm and its underlying code have not been disclosed, and successor studies that were carried out according to the original study of 2022 were easily used different versions of the test. In a study that the company published this year, a biomarker was removed from the original combination, for example, and three new ones were added This problem led to the French National Health Authority (HAS), an independent institution for evaluating health products, to reject Alcediag's application for the test by the French health authorities. "There were performance variations between the three versions, and we lacked the reason why this version was chosen and not another," says Cédric Carbonleil, who heads the Department of the HAS, which is responsible for the evaluation of new medical devices and procedures. It is not uncommon for companies to reject their applications in early development phases. The HAS expects Alcediag to make an application again, he adds. Alcediag explains that changes to the biomarkers have been made to improve the performance of the test and that the algorithm was not disclosed for commercial reasons.
Chaumette expresses that he would have liked larger studies to support the test before he was issued to patients, and he hopes that Alcediag will provide his technology independent groups to replicate the results. "If you quickly commercialize it and patent everything without sharing anything, it will be opaque."
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Salvetat, N. et al. Transl. Psychiatry 12, 182 (2022).