For nearly ten years, the FondaMental foundation has been following the largest cohort of patients with bipolar disorders 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 factors of poor prognosis.
An article to be found in Inserm magazine n°54
Without knowing it, everyone probably knows someone with bipolar disorder. One in 100 people, according to epidemiological studies, is indeed affected. 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 life, professional and emotional – and to depressive phases. Unfortunately, bipolar disorders are associated with a reduction in life expectancy of 10 years due to the associated risks of suicidal behavior, and comorbidities somatic such as cardiovascular diseases.
Despite this bleak picture, research on bipolar disorder is lagging behind. It is to address this gap that the FACE-BD cohort (FondaMental Advanced Center of Expertise 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’s teams, led by Marion Leboyer, who received the Grand Prix Inserm in 2021 for his discoveries on bipolar disorders in particular, took stock of this decade of cohort follow-up. And it is clear that knowledge has greatly progressed, on all levels: origin of the pathology, patient trajectories, links with cognition, treatments, observance from care…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 of the cohort, the researchers made decisive discoveries on the link between genetic and environmental factors. ” We have contributed to showing that bipolar patients are carriers of genetic variants especially the system Human Leukocyte Antigen (HLA) or receptor genes Tolllike (TLR) that make them more susceptible to environmental risk factors, such as infections, severe trauma, pollution, poor 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 changes to neurotransmitters. The discovery of these immuno-inflammatory abnormalities now opens the way to the identification of 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 the evolution of the patients », summarizes Marion Leboyer. ” We now know that there are three types of trajectoriesexplains Ophelia Godin, 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 functioning of the patient, that is to say his ability to lead a normal daily life, but also his cognitive functioning. ” We have discovered 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, appointments, etc.) and maintaining social relationships. satisfactoryreports 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 cognitive remediation, the objective of which is to improve the function to which the disorder relates. For verbal memory, the person trains to remember words, for example. »
Furthermore, the researchers are managed to identify factors that could help modify patient trajectoriesexplains Ophelia Godin. Those who follow a bad trajectory of functioning have more depressive syndromes, sleep disorders, greater weight and follow their treatment less well. It is therefore necessary to act on these factors as a priority. This notably involves the management of depression and recommendations on lifestyle, sleep, physical activity and a balanced diet. Parameters that seem to go without saying, and which are however as decisive as they are difficult to modify. Overweight is indeed common in these patients: nearly half are affected. At issue: a link between bipolar disorder and metabolic syndromea disorder that combines several disorders such as hypertension, diabetes or cholesterol.
The link with metabolic syndrome
” We have shown that the frequency of this syndrome is twice as high in individuals with bipolar disorder compared to the general population, with a prevalence between 20% and 24% “, reports Ophelia Godin. However, people with metabolic syndrome have an increased risk of developing diabetes or cardiovascular disease. ” These cardiovascular diseases are precisely the leading cause of death for bipolar patients, confirms the researcher. It is therefore essential to detect and manage them in order to improve the prognosis. »
But the question of treatment is delicate. Lithium, the most common and well-tolerated mood stabilizer, may require daily intake. Some psychotropic drugs promote weight gain. This type of constraint sometimes jeopardizes compliance, ie 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 rather 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 treatment follow-up, such as the intensity of depressive symptoms. In this case, the patient may lack motivation to adhere to the treatment. Sometimes the problem is cognitive: difficulty concentrating causes forgetfulness. Depression must therefore be taken care of. One of the solutions for improving compliance is also therapeutic education, which consists in better explaining to the patient the importance of the treatment. ” A third of patients respond very well to treatment and have no residual symptoms or relapse, which is very encouraging. “says Raoul Belzeaux.
The cost in question
All of these levers represent major advances in treatment. In order to convince the public authorities of their importance, the researchers assessed their medico-economic advantage. The direct costs (consultations, treatments, hospitalisation, day hospital, etc.) have been estimated at €7,565 per year and per patient. For patients who have followed a care dictated by these recent discoveries, the direct costs have decreased by 30 to 50% thanks in particular to a 50% reduction in rehospitalizations. The way is traced.
🔎 To learn more about bipolar disorders, see the Fondation FondaMentale file
Marion Leboyer is head of the Translational Neuropsychiatry team, at the Mondor Institute for Biomedical Research (unit 955 Inserm/Paris-Est Créteil University), in Créteil. Ophelia Godin is a research fellow in 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 the Timone Neuroscience Institute. (mixed research unit 7289 CNRS/Aix-Marseille University), in Marseille.
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