For almost ten years, the FondaMental foundation has been following the largest cohort of patients with bipolar disorder ever formed. The goal: to identify the markers of the different clinical forms of these very heterogeneous disorders and to analyze the trajectories of the disease in order to identify and correct the poor prognosis factors.
An article found in Inserm magazine n ° 54
Without knowing it, everyone probably knows someone with bipolar disorder. One in 100 people, according to epidemiological studies, he is really worried. It is the sixth leading cause of disability worldwide: patients are prone to manic phases – resulting in hyperactivity, euphoria and other behavioral disorders that have a major impact on social, professional and emotional life – and to depressive phases. Unfortunately, bipolar disorders are associated with a 10-year reduction in life expectancy due to the associated risks of suicidal behavior and comorbidities somatic diseases such as cardiovascular diseases.
Despite this gloomy picture, research on bipolar disorder is lagging behind. It is to bridge this gap that the FACE-BD cohort (FondaMental Advanced Competence Center for Bipolar Disorder) was created about ten years ago by the FondaMental foundation. To date, it includes 4,422 people with this disorder. In a recent publicationthe foundation teams, led by Marion Leboyer, who received the Grand Prix Insertion in 2021 for his findings on bipolar disorders in particular, he took stock of this decade of follow-up cohort. And it is evident that knowledge is very advanced, at all levels: origin of the pathology, patient trajectories, links with cognition, treatments, observance from the cure … the answers are emerging at a steady pace.
The immunoinflammatory pathway
On the causes, first of all. Thanks to the genetic and immunological analyzes carried out on the patients in the cohort, the researchers made decisive discoveries on the link between genetic and environmental factors. ” We helped show that bipolar patients are carriers of genetic variants especially the system Human leukocyte antigen (HLA) or receptor genes Countless (TLR) that make them more susceptible to environmental risk factors, such as infections, severe trauma, pollution, improper lifestyleexplains Marion Leboyer. Exposure to these factors triggers an inflammatory response that lasts over time and can lead to the activation of deleterious biological pathways, such as those of retrovirus endogenous, the production of self-antibodyor change to neurotransmitters. The discovery of these immune-inflammatory abnormalities now paves the way for identification biomarkers of homogeneous clinical forms of bipolar disorders, but also to the discovery of targeted treatments.
Trajectories to modify
” All the interest of the cohorts is to be able to study, over time, the prognosis and evolution of patients »Summarizes Marion Leboyer. ” We now know that there are three types of trajectoriesexplains Ophelia Godin, an Inserm researcher at the Mondor Institute for Biomedical Research in Créteil: patients who improve, those who do not improve, and those whose condition worsens over time. This evolution is measured by analyzing the patient’s functioning, that is his ability to lead a normal daily life, but also his cognitive functioning. ” We have found that cognitive deficits, such as verbal memory disorders, are subsequently accompanied by various functional difficulties that prevent them from carrying out simple daily activities (shopping, dating, etc.) and from maintaining satisfying social relationships.reports Paul Roux, psychiatrist and researcher at the Center for Research in Epidemiology and Population Health in Villejuif. In this case, it is possible to offer a cognitive remedy, the goal of which is to improve the function to which the disorder refers. For verbal memory, the person trains himself to remember words, for example. “
Besides, researchers are was able to identify factors that could help modify patient trajectoriesexplains Ofelia Godin. Those who follow a poor trajectory of functioning have more depressive syndromes, sleep disturbances, greater weight and follow their treatment less well. It is therefore necessary to act on these factors as a matter of priority. This specifically involves managing depression and recommendations on lifestyle, sleep, physical activity, and a balanced diet. Parameters that seem obvious, but which are however as decisive as they are difficult to modify. Overweight is in fact common in these patients: almost half are affected. Under discussion: a link between bipolar disorder and metabolic syndromea disorder that combines several ailments such as hypertension, diabetes or cholesterol.
The link with the metabolic syndrome
” We have shown that the frequency of this syndrome is double in individuals with bipolar disorder than in the general population, with a prevalence between 20% and 24% “, Reports Ofelia Godin. However, people with metabolic syndrome have a higher risk of developing diabetes or cardiovascular disease. ” These cardiovascular diseases are precisely the number one cause of death for bipolar patients, confirms the researcher. It is therefore essential to detect and manage them in order to improve prognosis. “
But the question of treatment is a delicate one. Lithium, the most common and well-tolerated mood stabilizer, may require a daily intake. Some psychiatric drugs promote weight gain. This type of constraint sometimes jeopardizes compliance, that is, the patient’s propensity to follow the doctor’s prescription. However, this has a strong influence on the prognosis of the disease. ” In the same patient, compliance is quite variablecomments Raoul Belzeaux, psychiatrist and researcher at the Timone Neuroscience Institute in Marseille. In a way, this is good news: it means that there are factors that can influence the follow-up of treatment, such as the intensity of depressive symptoms. In this case, the patient may not be motivated to adhere to the treatment. Sometimes the problem is cognitive: the difficulty in concentrating causes oblivion. Depression must therefore be treated. One of the solutions to improve compliance is also therapeutic education, which consists in better explaining the importance of treatment to the patient. ” One third of patients respond very well to treatment and have no residual symptoms or relapses, which is very encouraging. “Says Raoul Belzeaux.
The cost involved
All of these levers represent major advances in treatment. To convince public authorities of their importance, the researchers evaluated their medical-economic advantage. The direct costs (consultancy, treatment, hospitalization, day hospital, etc.) have been estimated at 7,565 euros per year and per patient. For patients who have followed a treatment dictated by these recent discoveries, direct costs have decreased by 30 to 50% thanks in particular to a 50% reduction in hospitalizations. The road is drawn.
🔎 To learn more about bipolar disorders, consult the factsheet of the Fondation FondaMentale
Marion Leboyer is in charge of the team Translation of neuropsychiatry, at the Mondor Institute for Biomedical Research (Unit 955 Inserm / University Paris-Est Créteil), in Créteil. Ophelia Godin is a researcher on this same team.
Paul Roux is a psychiatrist and researcher at the Center for Research in Epidemiology and Population Health (Unit 1018 Inserm / Institut Pasteur / University of Versailles-Saint-Quentin-en Yvelines) in Villejuif.
Raoul Belzeaux is a psychiatrist and researcher at theRudder Institute of Neuroscience (joint research unit 7289 CNRS / University of Aix-Marseille), in Marseille.
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