Menu

Against Whooping Cough and Its Transmission, a New Safe and Effective Nasal Vaccine

coqueluche - Colonies de Bordetella pertussis

Colonies of Bordetella pertussis, the agent of whooping cough, on an agar plate. © Camille Locht/Inserm

Highly infectious and potentially life-threatening in infants, whooping cough, caused by the bacterium Bordetella pertussis, continues to circulate to a large extent throughout the world. Although the vaccines currently used protect against the onset of symptoms, they have limited durability and cannot prevent bacterial infection resulting in transmission between individuals. An international research team including Camille Locht, Inserm research director at the Center for Infection and Immunity of Lille (Inserm/Institut Pasteur de Lille/Université de Lille/Lille University Hospital/CNRS), has demonstrated, in a phase 2 clinical trial, the efficacy and safety of a nasal vaccine for whooping cough in adults. The results of their study, sponsored by ILiAD Biotechnologies and to be published in The Lancet, suggest that this new vaccine, BPZE1, which is potentially capable of preventing bacterial colonization of the respiratory tract, constitutes a valuable asset when it comes to breaking the epidemic chains of transmission of the disease.

Whooping cough is an infectious respiratory disease caused by the bacterium Bordetella pertussis. Highly contagious, it is known for causing fatal complications in infants.

Since the late 1990s, although the Tdap vaccine[1] has been used in industrialized countries mostly to fight whooping cough, the immunity it provides decreases over time, requiring the administration of boosters. In addition, although it helps to prevent the onset of symptoms, it does not prevent infection by the bacterium itself or its transmission to others. Therefore, whooping cough epidemics persist throughout the world, despite high rates of vaccination.

The development of a new whooping cough vaccine, called BPZE1, aims to make up for the shortcomings of Tdap in order to better fight these epidemics. A particularity of this “live attenuated” vaccine (containing an attenuated version of the bacterium) is that it is administered nasally, thereby mimicking the natural modes of transmission and colonization of Bordetella pertussis in the mucous membranes of the respiratory tract.

An international research team including Camille Locht, Inserm research director at the Center for Infection and Immunity of Lille (Inserm/Institut Pasteur de Lille/Université de Lille/Lille University Hospital/CNRS), in collaboration with the company ILiAD Biotechnologies, conducted a study to evaluate the efficacy and safety (non-toxicity) of BPZE1 in a phase 2 clinical trial with 300 healthy adult US participants.

In this study, the participants were divided into two groups: the first group received one nasal dose of BPZE1 and one intramuscular dose of placebo and the second group received one intramuscular injection of Tdap and one nasal dose of placebo. Three months later, half the participants from each of the two groups received one dose of BPZE1 (to simulate an attenuated natural infection), while the other half received intranasal placebo.

The research team found that, while the Tdap vaccine induced the secretion of high levels of Bordetella pertussis immunity markers in the blood, BPZE1 induced consistent immunity in both the nasal mucosa and the blood. In addition, within 28 days of the second nasal administration, 90% of the participants having initially received BPZE1 had no bacterial colonies in the nose. In the remaining 10%, colonization was low (fewer than 260 colonies per mL of mucus). In comparison, 70% of the patients vaccinated with Tdap had significant nasal bacterial colonization (nearly 14,325 colonies per mL).

Moreover, the research team did not see any serious adverse side effects from vaccination during the study.

Therefore, according to Locht, “the benefit/risk profile of BPZE1 is favorable: just one nasal administration induces safe and well-tolerated strong and long-lasting immunity, in both the blood and respiratory tract. And unlike Tdap, BPZE1 protects the mucous membranes from colonization by the bacterium”.

Indeed, given that Bordetella pertussis infects the respiratory tract and multiplies in its mucosa, immunity at this level could be essential in preventing epidemics of whooping cough.

“As this bacterium is highly infectious to humans, it is critical that a vaccine does not only target the prevention of disease but also the transmission of its causative bacterium and the speed at which the body eliminates it,” adds Locht, “which makes BPZE1 a relevant tool for preventing whooping cough infections and reducing the epidemic chains of transmission.”

Given that the participants in the aforementioned study were all adults over the age of 18, another study is ongoing to evaluate the efficacy and safety of BPZE1 in school-age children, as schools are a critical location for transmission of the disease.

More About the Development and Evaluation of BPZE1

In 2008, the European project CHILD-INNOVAC was launched under the auspices of Inserm in collaboration with 10 European partners, with the aim of developing an innovative nasal vaccine against whooping cough. This was the context for the development and patenting of the BPZE1 vaccine by a team from Inserm and Institut Pasteur de Lille led by Inserm research director and project coordinator, Camille Locht. In 2014, the research team published in PLOS ONE the first work evaluating the efficacy and safety of BPZE1 in a phase 1 clinical trial, following examination of the data by an Independent Data Monitoring Committee. An agreement was then reached between the Inserm Transfert platform, tasked with creating value from the intellectual property related to BPZE technology, and ILiAD Biotechnologies, in order to continue the development and evaluation of the vaccine. In 2020, a new phase 1 study conducted in collaboration with ILiAD Biotechnologies, and published in The Lancet Infectious Diseases, reinforced the clinical results from 2014 on the vaccine’s efficacy and safety.

[1] Tdap is an “acellular” vaccine, which does not contain whole bacteria but only certain proteins derived from Bordetella pertussis, which have the particularity of triggering a blood immune response. It combines vaccines against whooping cough, diphtheria, and tetanus, and is administered in France in three intramuscular doses to infants at 2, 4, and 11 months of age. Three boosters are recommended at around 16 months, 11 years and 26 years of age. Although better tolerated, it is more expensive and less effective than the whole cell pertussis vaccine (that contains the inactivated bacteria), which is still being used today in many low- and middle-income countries.

Pre- and Postnatal Chlordecone Exposure Could Affect the Cognitive Development and Behavior of Children

Chlordécone

Chlordecone is an organochlorine insecticide that was used in the French West Indies from 1973 to 1993 to control the banana root borer. © Adobe Stock

Despite the fact that chlordecone has not been used as an insecticide in the French West Indies for 30 years now, its persistence in the environment continues to contaminate the populations. While its neurotoxic properties are well established, its impact on neurodevelopment remains to be clarified. An international research team involving Inserm researchers at the Research Institute for Environmental and Occupational Health (Inserm/Université de Rennes/EHESP School of Public Health) studied the impact of pre- and postnatal chlordecone exposure on the cognitive and behavioral abilities at 7 years of age of 576 children from the TIMOUN mother-child cohort in Guadeloupe[1]. Their research shows that this exposure is associated with poorer scores on tests evaluating cognitive abilities and behavioral disorders, with the impact differing according to the child’s sex. These results, published in Environmental Health, call for consideration to be given to the potential impact of these effects at population level, in order to optimize prevention policies.

Chlordecone is an organochlorine insecticide that was used in the French West Indies from 1973 to 1993 to control the banana root borer. Its persistence in the environment is responsible for contaminating the population through the consumption of contaminated foodstuffs. Chlordecone is now considered to be neurotoxic, toxic to reproduction and development, carcinogenic, and an endocrine disruptor. Experimental studies in animals have also shown that exposure of females to chlordecone during gestation leads to neurobehavioral and learning disorders in the offspring, the nature and intensity of which varies according to sex.

The neurotoxicity of chlordecone can be explained by its ability to interact with numerous neurotransmitters[2] and by its hormonal properties, particularly its action on estrogens. Yet estrogens play a crucial role, which differs according to chromosomal sex, in the development of the brain.

In the face of these observations, and in order to better estimate the potential impact of pre- and postnatal exposure to chlordecone on child neurodevelopment, Inserm researchers from the Research Institute for Environmental and Occupational Health (Inserm/Université de Rennes/EHESP School of Public Health), as part of an international research team, examined the intellectual abilities and behaviors of 576 children from the TIMOUN mother-child cohort in Guadeloupe.

In order to assess the children’s levels of pre- and postnatal exposure to chlordecone, the concentration of the pesticide was measured in umbilical cord blood at birth and in the blood of the children at 7 years of age. Their intellectual abilities were assessed according to 4 criteria: verbal comprehension, information processing speed, working memory[3], and perceptive reasoning[4].

The mothers also completed a questionnaire to measure the presence of behavioral difficulties in their child which can be categorized as either “internalizing” – in the form of emotional symptoms and interpersonal problems with peers, or “externalizing” – in the form of social behavior problems (anger, defiance, etc.), hyperactivity, and/or inattention.

Prenatal exposure to chlordecone was found to be associated, for each doubling of the level of exposure, with a 3% increase in the score estimating “internalizing” behavioral difficulties at 7 years of age, with a stronger association among girls (+7%) than among boys (0%).

Postnatal chlordecone exposure was found to be associated with poorer scores estimating general intellectual abilities (0.64 IQ point decrease for each doubling of the level of exposure). This manifests, particularly in boys, as a decrease in perceptive reasoning, working memory and verbal comprehension. In addition, postnatal exposure was associated with a greater number of “externalizing” behavioral difficulties in both boys and girls.

These findings indicate that exposure to chlordecone during periods of in utero development or during childhood is associated with a reduction in intellectual abilities and an increase in behavioral difficulties, with effects sometimes differing in nature and intensity according to sex.

“This is consistent with the estrogenic properties of this pesticide and its effects that vary according to sex and period of brain development,” explains Luc Multigner, Inserm research director who participated in this research.

According to the research team, it is therefore justified to pursue public policies aimed at reducing exposure to chlordecone, particularly among the most vulnerable populations, such as children and pregnant women. The team also calls for monitoring of the prevalence and management of children presenting with psychomotor retardation, sensory, neuromotor or intellectual disorders and/or interpersonal difficulties.

Although the neurological and neurobehavioral effects observed in this study are relatively moderate and subtle at the individual level, they may, given the widespread exposure of the French West Indian population to chlordecone, have a non-negligible impact at the population level,” concludes Multigner.

 

[1] The TIMOUN mother-child cohort was designed to evaluate the health impact of chlordecone exposures on pregnancy and childhood development. Led by the Research Institute for Environmental and Occupational Health (Inserm/Université de Rennes/EHESP School of Public Health) and the Gynecology-Obstetrics Department of University Hospital Guadeloupe, this cohort consists of 1,068 women included during their pregnancy between 2004 and 2007. Following their birth, the children were monitored at 3, 7 and 18 months of age and then at 7 years of age.

[2] Neurotransmitters are chemical substances that ensure the transmission of information between nerve cells.

[3] Working memory is a form of short-term memory that uses the information obtained in the present moment in the performance of a specific task.

[4] Perceptive reasoning measures the cognitive ability to integrate and manipulate visual and spatial information in order to solve complex visual problems.

Cannabis: Insomnia Twice as Common Among Students Who Use It Every Day

The likelihood of suffering from insomnia was found to be 45% higher in cannabis users compared to non-users. © Unsplash

In France, over half of students suffer from sleep complaints. These are particularly concerning as they can affect the success of their studies, and their physical and mental health. A real public health issue, the evaluation of these health risks is one of the research subjects of a team of scientists from Inserm, Université de Bordeaux and Bordeaux University Hospital. In a new study published in Psychiatry Research, they focused on cannabis use by students – with the knowledge that its consumption among 18-25-year-olds in France is particularly high – and tried to measure its effects on sleep. What they found was that cannabis use increased the risk of sleep disturbances, with the frequency of insomnia doubling among those who smoke it daily. This study was conducted based on the analysis of the data of 14,787 student volunteers, who are members of the i-Share cohort.

Poor sleep quality has been shown to affect 55% of students and insomnia 19%. These sleep alterations are all the more concerning because of their detrimental effects on mental health, physical health, and cognitive capacities – with a subsequent negative impact on the students’ academic success.

Some studies have already investigated the causes of these disturbances, particularly in relation to cannabis use, the level of which is particularly high among young people in France: 13.9% of 18-25-year-olds report using it monthly and 4% daily[1].

In this new article, researchers from Inserm, Université de Bordeaux and Bordeaux University Hospital at the Bordeaux Population Health research center have for the first time conducted an in-depth analysis of the association between cannabis use and sleep disturbances in a sample of 14,787 university students. These participants all come from the i-Share cohort that studies the general health of students, which is led by the last author of this study, Christophe Tzourio.

The students answered an online self-questionnaire on the frequency of their cannabis use over the past year (daily, weekly, monthly or rarely/never), as well as the quality of their sleep in the last three months[2], with a question specifically about insomnia. Other questions concerned their sociodemographic characteristics, lifestyle (e.g. alcohol or tobacco consumption) and mental health, in order to refine the analysis and avoid any bias or confounding factors.

The results of this study confirm the existence of an association between cannabis use and sleep disturbances, particularly insomnia, among students. The likelihood of suffering from insomnia was found to be 45% higher in cannabis users compared to non-users, reaching a 2-fold higher likelihood compared to never/rarely users.

 “The originality of this study lies in the fact that we had access to a particularly large sample of students who provided accurate data on their cannabis use and sleep quality. The richness of the data collected through the questionnaires provides new evidence of the association between insomnia and cannabis use,” explains Julien Coelho, first author of the study.

 

“Although causality cannot be confirmed with certainty, these findings suggest the importance of stepping up public health messages for the purposes of prevention among students, as well as raise the awareness of health professionals on the dangers of high levels of cannabis use on the health of young people,” concludes Tzourio.

 

[1] Source: Santé publique France Health Barometers, with data utilization by the French Monitoring Centre for Drugs and Drug Addiction (OFDT)

[2] The questions focused on four items: insomnia, sleepiness, poor sleep quality, and sleep deprivation. 

Obesity and Overweight: Almost One in Two French People Affected. Current Situation, Prevention and Therapeutic Solutions

balance

© Photo i yunmai / Unsplash

Obesity is a global public health problem whose incidence continues to increase. According to the World Health Organization (WHO), the number of cases worldwide has almost tripled since 1975.

Obesity is associated with many comorbidities and has a high rate of mortality. This complex chronic disease is therefore estimated to increase the risk of cardiovascular disease (the leading cause of death worldwide), diabetes, musculoskeletal disorders, many forms of cancer (endometrial, breast, ovarian, prostate, liver, gallbladder, kidney, colon, etc.). More recently, data have shown that people with obesity are more susceptible to severe forms of COVID-19. Its impact on population health and its economic and social costs are therefore considerable.

This major public health issue is also one that affects France. In order to evaluate the impact of preventive measures such as the country’s National Nutrition and Health Program (PNNS), it was important to take thorough stock of the current epidemiological situation. The latest study on the subject, on the initiative of the French League Against Obesity and coordinated by researchers from Inserm and Montpellier University Hospital, was published in February in the Journal of Clinical Medicine. Based on the figures collected by the Odoxa polling institute, this study reveals the extent of the problem in highlighting that 47.3% of French adults are obese or overweight. It also provides specific information on the most affected populations by age group, region and socioprofessional activity, making it possible to refine prevention policies.

And beyond these prevention measures that are crucial to fighting obesity, how can we support individuals who are overweight or obese? While lifestyle interventions, particularly diet and physical activity, are essential, appropriate management is based on multidisciplinary and personalized approaches that also incorporate solutions in the form of medication, surgery, or both. Much progress has been made in recent years in the field of medication, as described in a literature review published in The Lancet, to which contributed Karine Clément, professor of nutrition and director of the Inserm unit Nutrition and Obesities: Systemic Approaches (Nutriomics).

Overweight and Obesity: Definition Elements

Obesity is defined by excessive body fat and modification of the adipose tissue, which cause health problems and can reduce life expectancy. Its causes are complex. It is the result of several factors – dietary, genetic, epigenetic and environmental – that come together and influence the development and progression of this chronic disease.

Adults are considered to be overweight when their body mass index (BMI) is equal to or greater than 25 and obese when their BMI is equal to or greater than 30. For children, age must be taken into account when defining overweight and obesity.

Read our special feature on obesity (only available in French).

The Latest Figures for France

Obépi-Roche is the name given to a series of surveys which had been coordinated by Inserm every three years between 1997 and 2012 in order to produce estimates of overweight and obesity prevalence in France. A new edition of this survey was launched by the French League Against Obesity in 2020, based on questionnaires collected by the Odoxa polling institute on a sample of 9 598 people living in mainland France, aged 18 years or older, and built using the quota-sampling method[1]. Coordinated by Annick Fontbonne, researcher at Inserm and David Nocca, doctor at Montpellier University Hospital, the analysis of the results reveals a worrying situation.

It showed that the prevalence of excess weight (which includes both overweight and obesity) was 47.3%, with 17% of subjects being obese. At first glance, these figures do not appear to be very different from the last estimates of the Obépi-Roche study of 2012. However, if we bear in mind the trends since 1997 and consider overweight and obesity separately, the observation is less favorable.

Since 1997, the prevalence of overweight has always fluctuated at around 30%, whereas that of obesity has continued to rise rapidly, from 8.5% in 1997 to 15% in 2012, and then to 17% in 2020. This increase is even more marked in the youngest age groups and for morbid obesity, whose prevalence had multiplied by around seven over the period.

“So we have to note that contrary to the expectations of public authorities and health professionals alike, obesity in France has continued to grow year on year since the rollout of the PNNS in 2001,” emphasize Annick Fontbonne and David Nocca.

The researchers went further in the analysis by highlighting differences in prevalence according to sex and age, region, and socioprofessional category.

Sex and Age

Older people are more overweight or obese than their younger counterparts, with excess weight affecting 57.3% of people aged 65 years and over compared to 23.2% of 18-24-year-olds. Nevertheless, the trends are more worrying, given that the youngest age groups have had the highest prevalence of obesity over the years. Since 1997, obesity among the 18-24-year-olds has more than quadrupled, and has almost tripled among the 25-34-year-olds, while the increase among those aged 55 and older has been low since 2009.

Differences between the sexes have also been observed. In 2020, while men were more often overweight than women (36.9% vs. 23.9%, respectively), the opposite was the case for obesity (16.7% vs. 17.4%, respectively).

obésitéEvolution of the prevalence of obesity by age groups between the 1997-2012 Obépi-Roche surveys and the 2020 Obépi survey.

 

Regional Disparities

The prevalence of obesity in 2020 exceeds 20% in north and northeastern France, and is the lowest (below 14.5%) in Île-de-France and Pays de la Loire. If we exclude the latter two regions and Brittany, we see a decrease in the prevalence gradient when moving from the northern to the southern regions of France.

obésitéGeographic distribution of the prevalence of obesity in 2020 in the French regions

 

Socioprofessional Categories

The scientific literature reveals that overweight and obesity are generally more common in the disadvantaged social categories. The Obépi 2020 study confirms this observation for the occupational qualification criterion, as the prevalence of excess weight is 51.1% among factory workers or equivalent, 45.3% among clerks, 43% among people in intermediate jobs, and 35% among managers or people in equivalent positions.

The trend is the same when we look at obesity: while the figures are similar for factory workers or equivalent (18%) and clerks (17.8%), they are markedly lower among managers or people in equivalent positions (9.9%). The intermediate jobs have a prevalence of obesity of 14.4%. It should also be noted that the trends have been increasing since 1997 in all occupational categories.

The authors conclude: “The study had been much awaited in order to obtain a rigorous overview of overweight and obesity in France. When compared to previous surveys, it has shown that although the prevalence of excess weight (overweight and obesity) is appearing to plateau, the prevalence of obesity is increasing rapidly and has doubled since 1997. In addition, the slope is more pronounced in younger generations and for the most severe degrees of obesity. Given the slight differences in methodology between the 1997-2012 and 2020 surveys, it would be desirable to repeat this series of surveys in order to confirm and monitor these worrying trends. “

 

Managing Obesity: Innovative Multidisciplinary Approaches

While prevention is the cornerstone in the fight against obesity and its associated comorbidities, it is also necessary to recognize that it is a complex chronic disease, to which therapeutic responses should also be provided.

The goal of obesity management is to improve health. Sustained weight loss of more than 10% overall bodyweight improves many of the complications associated with obesity (e.g. prevention and control of type 2 diabetes, hypertension, fatty liver disease, cardiovascular diseases and obstructive sleep apnea), as well as quality of life.

However, maintaining the weight loss is the major challenge of obesity management. Like all complex chronic diseases, obesity depends on factors that vary from one individual to another and managing it requires a long-term, multimodal approach, taking into account each individual’s treatment goals, and the benefits and risks of the different therapies.

Lifestyle interventions (dietary habits, physical activity/inactivity, sleep, psychological difficulties, etc.) form the first pillar of this management, but they are rarely sufficient in achieving and maintaining significant long-term weight loss. Depending on individual situations, management can therefore be combined with other strategies that include anti-obesity medications and bariatric surgery.

 

Medication

Most available “historical” anti-obesity medications work on neurotransmitters (such as serotonin) that act on appetite regulation and reward circuits, in order to reduce hunger, promote the feeling of satiety, and decrease the reward sensation associated with food. Many of these treatments have had to be withdrawn due to side effects, leaving patients and their doctors without pharmacological tools.

However, over the past five years, significant therapeutic advances have led to the development of a new generation of anti-obesity medications. These new treatments, which are similar to the intestinal hormones (incretins) and also used in combination with other molecules (GLP1, GIP, etc.), are highly effective. They are associated with weight losses of more than 10% of overall bodyweight in more than two-thirds of clinical trial participants. Known for their initial actions on the pancreas by promoting the secretion of insulin, they also act on satiety mechanisms in the central nervous system. Long-term data on safety, efficacy, and cardiovascular outcomes are awaited in order to make progress in bringing these medications to market.

These advances also concern a new targeted treatment for rare and very severe forms of genetic obesity that begin in childhood. This treatment induces weight loss by acting on the serious eating disorders experienced by these patients and leads to an improvement in their quality of life and that of those around them.

 

And What About Surgery?

Long-term studies have shown that bariatric surgical procedures typically lead to a durable weight loss of 25% and rapid, sustained improvements in complications of obesity and in mortality. Less invasive endoscopic techniques are also possible in some cases. However, the surgical approach, more invasive than medication, has not yet been compared to the new-generation anti-obesity treatments.

“Further work is required to determine optimal patient-specific treatment strategies, including combinations of lifestyle interventions, anti-obesity medications, endoscopic and bariatric surgical procedures, and to ensure equitable access to effective treatments for these complex pathologies,” concludes Clément, co-author of the literature review published in The Lancet.

 

[1]The quota method is a sampling method that consists of ensuring the representativeness of a sample by assigning it a structure similar to that of the general population.

Reproductive Life Factors and Hormone Therapy May Affect Women’s Risk of Parkinson’s Disease

Parkinson

© AdobeStock

The specific risk factors for the development of Parkinson’s disease in women remain little studied and poorly known. Exposure to the hormones involved in female reproductive life is one of the avenues explored at the Epidemiology and Population Health Research Center (CESP) by a research team from Inserm, Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines with Institut Gustave Roussy, which compared the reproductive characteristics of nearly 1,200 women with Parkinson’s disease with those of other women from the E3N cohort[1]. Their findings show that age at first menstrual period, number of pregnancies, type of menopause and a molecule used to improve fertility are associated with a higher risk of developing the disease. This research, published in Brain, supports the role of hormonal exposures during the reproductive life of women – particularly estrogen levels – in Parkinson’s disease and opens up avenues for targeted prevention strategies.

Parkinson’s disease is a progressive neurodegenerative disease promoted by complex interactions between genetic and environmental factors. It currently affects more than 6 million people worldwide and is 1.5 times more common in men. It is also comparatively less well known and studied in women. As such, studies on certain specifically female risk factors, such as impact of exposure to the hormones related to reproductive life, whether natural (puberty, menstrual cycles, pregnancies, menopause…) or medical (hormone treatments used for contraception, to increase fertility, or post-menopause, for example), remain few in number and contradictory.

Within the Exposome, heredity, cancer and health research team at the Epidemiology and Population Health Research Center (CESP) (Inserm/Université Paris-Saclay/Université de Versailles Saint-Quentin-en-Yvelines), Inserm researcher Marianne Canonico, in collaboration with fellow Inserm researcher Alexis Elbaz, evaluated the influence of reproductive life and the use of hormone treatments on the risk of Parkinson’s disease in women. This involved examining numerous characteristics relating to the reproductive history of almost 1,200 women from the E3N cohort, in whom Parkinson’s disease was diagnosed during the 24 years of their follow-up and comparing them with those of the other women in the cohort.

The scientists were able to observe several characteristics associated with an increased risk[2] of developing the disease, the effects of which proved to be cumulative[3].

As such, those women whose first menstrual period occurred before or after 12-13 years of age showed an increased risk of +21% and +18%, respectively. However, the duration and regularity of the menstrual cycle showed no significant impact.

“It is the first time that such an association has been shown between age at first menstrual period and Parkinson’s disease, explains Canonico, one explanation for which could be – during this crucial time for neurodevelopment that is puberty – interference of the sex hormones with the neural circuits involved in the development of the disease. “

Another characteristic observed: although having or not having children was not associated with the risk of developing the disease, among those women having had children, this risk increases with the number of births (+22% with the second child and +30% starting from the third).

While being menopausal did not appear to be directly associated with an increased risk of Parkinson’s disease, the type of menopause did. Artificial menopause was found to be associated with a 28% increased risk compared to natural menopause, which is higher if it occurs before the age of 45 (+39% risk compared to menopause occurring after the age of 45) or when it is the result of both ovaries being removed – with or without the uterus[4] (+31% compared to natural menopause).

Finally, while fertility treatments were not globally associated with an increased risk of Parkinson’s disease, when looked at individually, clomiphene – used to stimulate ovulation – was found to increase the risk by 80% compared with women who had never taken fertility treatment.

In the two previous cases, exposure to insufficient levels of female hormones (estrogens) could be responsible:

“Artificial and/or early menopause causes ovarian insufficiency and consequently a sudden and anticipated fall in the levels of estrogen, which are usually still elevated before the age of 45, explains Canonico, and, as for clomiphene, it has an anti-estrogen role.” 

This hypothesis is supported by the observation of a protective effect of hormone therapies used at menopause, which appear to attenuate the risk related to early or artificial menopause for Parkinson’s disease.

“These results are consistent with the knowledge of the neuroprotective role of estrogens, which has already been demonstrated in other studies,” adds Canonico.

Although this study has the largest cohort of female Parkinson’s disease patients to date, the researchers point out that the results related to the identified risk factors must be confirmed by long-term studies with more participants. These findings could ultimately help identify groups that are at high risk, within which prevention strategies could be proposed at an early stage.

 

[1]The E3N cohort, sponsored by Inserm, Université Paris-Saclay and Institut Gustave Roussy, is the first large-scale French study on women’s health. Since 1990, nearly 100,000 French women have been followed up as part of this vast prospective study.

[2]However, breastfeeding, use of oral contraceptives, and duration of reproductive life were not found to have any association with the onset of Parkinson’s disease.

[3]A cumulative effect was observed for the risk criteria mentioned later in the text. Therefore those women having cumulated early or late puberty, several pregnancies and an artificial and early menopause had the highest risk of developing the disease.

[4]On the other hand, artificial menopause triggered by removal of just the uterus was associated with a more moderate increase in risk. 

Dietary Exposure to Nitrites Associated with Increased Type 2 Diabetes Risk

nitrites - charcuterie

In addition to their role in food preservation, nitrites and nitrates give a pink color to ham and other processed meat products. © Adobe Stock

More than 15,000 packaged products on the French market currently contain nitrites or nitrates. Although commonly used to ensure better preservation of processed meats (ham, sausages, etc.), the safety of these food additives is the subject of debate. Nitrites and nitrates are also naturally found in various foods (particularly vegetables) and in drinking water, but agricultural and industrial practices can increase their levels.

Researchers from Inserm, INRAE, Université Sorbonne Paris Nord, Université Paris Cité and Cnam, as part of the Nutritional epidemiology research team (EREN-CRESS), studied the role of dietary nitrites and nitrates in the development of type 2 diabetes. The scientists analyzed data on the health and exposure to nitrites/nitrates of 104,168 French adults participating in the NutriNet-Santé cohort study. While their statistical analyses suggest an association between the consumption of nitrites and increased type 2 diabetes risk, no such link has been found with nitrates. Their findings have been published in PLOS Medicine.

Nitrites and nitrates are naturally present in certain foods (particularly vegetables) as well as in water and soil – a phenomenon that can be increased by agricultural and industrial practices. These compounds are therefore found in our diet.

Commonly used as additives to increase the shelf lives of certain foods such as processed meat, their antimicrobial role makes it possible to limit the development of pathogenic bacteria that cause certain food-borne infections. They also give a pink color to ham and other processed meat products. Over 15,000 packaged products on the French market currently contain added nitrites or nitrates.

This is despite recommendations by several public health authorities to limit the use of nitrites and nitrates as food additives due to their probable impact on colorectal cancer risk[1]. Although previous experimental studies had already suggested an association between exposure to nitrites and nitrates and the onset of metabolic dysfunction, epidemiological and clinical data remain sparse.

In order to learn more about the subject, a research team from Inserm, INRAE, Université Sorbonne Paris Nord, Université Paris Cité and Cnam consulted the data collected from 104,168 participants in the NutriNet-Santé prospective cohort (see box below).

The cohort volunteers had given details of their food consumption by sending the scientists full records of their meals over several 24-hour periods, including the names and brands of the products. This enabled the team to assess their exposures to nitrate and nitrite additives, with high levels of precision. In addition, this information was supplemented by control data provided by the health authorities, which shed light on the volunteers’ levels of exposure to nitrites and nitrates of non-additive origin – i.e. via water and soil – according to their location within France.

The scientists also had access to data on the medical history of the participants, their physical activity, lifestyle and health status, and their sociodemographic information. The participants studied here did not have type 2 diabetes when they joined the study, and they were followed between 2009 and 2021 to monitor for its development.

The researchers conducted statistical analyses in order to study the associations between exposures to nitrites and nitrates – in both food additive and non-additive form – and the risk of type 2 diabetes.

Those participants with a greater exposure to nitrites – specifically from food additives but also non-additive sources – presented a higher risk of developing type 2 diabetes.

In this study, there was a 27% increased risk for those with the highest consumption of total nitrites compared to those with the lowest, representing a 53% increase for those whose nitrites came mostly from additives and 26% for those whose nitrites came from other sources.

No association between exposure to nitrates and type 2 diabetes risk was found.

The results also did not support any potential benefits for dietary nitrites or nitrates in type 2 diabetes prevention.

“This is the first large-scale cohort study that suggests an association between additive nitrites and a potentially increased risk of type 2 diabetes,” explain Bernard Srour, post-doctoral researcher at Inserm, and Mathilde Touvier, Inserm research director, who led this study.

 

“These results provide new evidence in the context of current discussions on the need for a reduction in the use of nitrite additives in processed meats by the food industry, and could also support the need for better regulation of soil contamination by fertilizers. In the meantime, several public health authorities worldwide already recommend citizens to limit their consumption of food containing controversial additives, among which sodium nitrite,” conclude the two scientists.

NutriNet-Santé is a public health study coordinated by the Nutritional epidemiology research team from the Center of research in epidemiology and statistics (EREN-CRESS, Inserm/INRAE/Cnam/Université Sorbonne Paris Nord/Université Paris Cité) which, thanks to the commitment and loyalty of over 170,000 participants (known as Nutrinautes), advances research into the links between nutrition (diet, physical activity, nutritional status) and health. Launched in 2009, the study has already given rise to over 250 international scientific publications. In France, a drive to recruit new participants is still ongoing in order to continue to further research into the relationship between nutrition and health.

By devoting a few minutes per month to answering questionnaires on diet, physical activity and health through the secure online platform etude-nutrinet-sante.fr, participants in France contribute to furthering knowledge of the links between diet and health.

[1] Anses report on the risks associated with the consumption of nitrites and nitrates filed in July 2022.

Predicting the Onset of Anxiety Disorders in Adolescence Thanks to Artificial Intelligence

Anxiété

Anxiety disorders are the most common psychiatric conditions in adolescence, with nearly one in three individuals affected. © Adobe Stock

Anxiety disorders are the most common psychiatric conditions in adolescence, with nearly one in three individuals affected. Some of these disorders – such as panic disorder or generalized anxiety disorder[1] – tend to emerge slightly later in life or consolidate in early adulthood. Therefore, identifying those who are at high risk of developing clinical anxiety (which meets specific diagnostic criteria) is crucial. For the first time, a team led by Inserm researchers Jean-Luc Martinot and Éric Artiges at the Developmental Trajectories and Psychiatry laboratory (Inserm/ENS Paris-Saclay) and the Borelli Center[2] (CNRS/Université Paris-Saclay) looked for factors that would predict the onset of anxiety disorders in adolescence. They monitored the mental health of a group of adolescents aged 14 to 23. Thanks to artificial intelligence, they have identified the warning signs most predictive in adolescence of the onset of anxiety disorders in these young adults. The results of this study have been published in Molecular Psychiatry.

A person is considered to suffer from an anxiety disorder when they experience intense and long-lasting anxiety that has no relation to an actual danger or threat, and which disrupts their usual functioning and daily activities. These disorders, which are encountered very frequently in the general population (with around 21% of adults thought to be affected at least once in their lifetime), often begin in childhood or adolescence. Therefore, being able to better identify them in these age groups would avoid worsening of the symptoms over the course of life.

While previous studies have highlighted the predictive power of artificial intelligence in psychiatric diseases such as depression and addictions[3], none had looked for predictors of anxiety disorders.

Researchers at the Developmental Trajectories and Psychiatry laboratory (Inserm unit 1299) at the Borelli Center (CNRS unit 9010) sought to detect warning signs in adolescence of the onset of anxiety disorders in adulthood.

In order to do this, the scientists monitored a group of over 2,000 European adolescents who were 14 years of age at the time of their inclusion in the Imagen cohort[4]. The volunteers all completed online questionnaires on their psychological health when they were 14, 18 and 23 years of age. Monitoring the volunteers over time made it possible to measure changes in the anxiety diagnosis.

An in-depth statistical learning study based on an artificial intelligence algorithm then determined whether some of the responses given in adolescence (at age 14) had an incidence on the individual diagnosis of anxiety disorders in adulthood (at age 18-23).

The researchers identified three major predictors or warning signs which, when present in adolescence, significantly increase the statistical risk of anxiety disorders in adulthood. These are neuroticism, hopelessness, and emotional symptoms.

 

Neuroticism designates the persistent tendency to feel negative emotions (fear, sadness, awkwardness, anger, guilt, disgust), as well as poor impulse control and poor ability to manage stress.

Despair is associated with low scores on the questionnaires evaluating optimism and self-confidence.

Emotional symptoms cover responses to the questionnaires indicating symptoms such as “headache/stomachache”; “a lot of worries, often worried”; “often unhappy, down or tearful”; “nervous in new situations, easily loses confidence”; “is easily afraid”.

 

Part of the study was also given over to observing the brains of the volunteers using magnetic resonance imaging (MRI). As brain development involves a change in the volume of different brain regions in adolescence, the researchers wanted to identify in these images a possible change in gray matter volume that could be predictive of future anxiety disorders.

While the imaging did not improve the prediction of anxiety disorders in their entirety compared to just the data from the questionnaires, it could enable a more precise determination of the type of anxiety disorder that an individual is likely to develop.

“Our study reveals for the first time that individualized prediction of the onset of future anxiety disorders in adolescence is possible. These identified predictors or warning signs could make it possible to detect people at risk earlier on and offer them an appropriate and personalized intervention, while limiting the progression of these diseases and their impacts on daily life,” explains Jean-Luc Martinot, Inserm research director and child psychiatrist, co-author of the study.

troubles anxieux

 

[1] There are several types of anxiety disorder: generalized anxiety, panic disorder, specific phobias, agoraphobia, social anxiety disorder, and separation anxiety disorder.

[2] Applied mathematics research center

[3] Whelan R., Watts R., Orr C. et al. Neuropsychosocial profiles of current and future adolescent alcohol misusers. Nature 512, 185-189 (2014).

[4] Imagen is a European cohort study that enrolled 2,223 adolescents at age 14 between 2008 and 2011. It is composed of young people from the general population and not patients.

Fathers Who Take 2 Weeks Paternity Leave Are Considered Less Likely to Develop Postpartum Depression

 

© Photo Omar Lopez sur Unsplash

In the weeks that follow the birth of a child, both parents are likely to develop depression. Paternity leave, recognized for its benefits on family balance, child development and male-female equality, could be one of the keys to preventing this condition that affects one in ten fathers and almost two in ten mothers. Using data from over 10,000 heterosexual couples participating in the Elfe[1] cohort study, a team of researchers from Inserm and Sorbonne Université at the Pierre Louis Institute of Epidemiology and Public Health looked at the impact of two weeks of paternity leave on the risk of postpartum depression in each parent. While the findings show that fathers who have taken or intend to take paternity leave are less likely to develop postpartum depression, this risk appears to be increased in mothers whose partner has taken paternity leave. This research, to be published in Lancet Public Health, supports the importance of family policies targeted at fathers and questions the modalities of paternity leave that is beneficial to the mental health of both members of the couple.

Postpartum depression is a common phenomenon among new parents: in healthy people, 17% of mothers and more than 10% of fathers are likely to develop it in the year following their child’s birth. For some parents, the onset of a depressive episode at this crucial period in family and social life heralds the development of depressive disorders that may persist over time.

Following the European Union Work-life Balance Directive in 2019, the European Parliament has encouraged policies to promote the equal sharing of parental and domestic tasks between mothers and fathers. Paid paternity leave is considered to be one of the policies likely to meet this objective, with studies already showing a link with increased participation by fathers in household tasks and child education, that it improved dynamics within the family and the couple, and that it had positive consequences on the emotional, psychological, and social development of the child. In addition, research has shown that, among new parents, feeling socially supported and declaring oneself to be globally satisfied with their relationship with their partner was associated with a reduction in the risks of postpartum depression.

To consolidate the existing data, a research team led by Maria Melchior, Inserm Research Director at the Pierre Louis Institute of Epidemiology and Public Health (Inserm/Sorbonne Université), sought to observe the impact of taking two weeks’ paternity leave (paid and with no risk of job loss)[2] on the risks in both parents of developing depression two months after the birth of their child.

To do this, the researchers used data from the Elfe cohort study, which includes more than 13,000 French mothers and nearly 11,000 French fathers whose children were born in 2011.

Each participating couple indicated whether the father had taken or intended to take paternity leave[3]. Two months after the birth of the child, the participants all completed a questionnaire to evaluate whether they were suffering from depression. Their responses were analyzed taking into account a certain number of socioeconomic (related to employment) and family health characteristics likely to influence the use of paternity leave.

At 2 months, over 64% of the fathers had already taken paternity leave, 17% reported that they intended to take it and almost 19% had not taken and did not intend to take paternity leave. 4.5% of the fathers who took paternity leave and 4.8% of those intending to take it had postpartum depression compared with 5.7% of those who did not use it.

However, the opposite phenomenon was observed in the mothers: 16.1% of the mothers whose partner had taken paternity leave presented postpartum depression compared with 15.1% of those whose partner intended to take paternity leave, and 15.3% of those whose partner had not taken paternity leave.

Thus, while the fathers who take or intend to take two weeks’ paternity leave have a reduced risk of postpartum depression, in mothers, the taking of paternity leave by their partners does not appear to have a significant beneficial effect.

“In addition to the benefits that paternity leave can have in terms of family dynamics and child development, it could also have positive effects on the fathers’ mental health, comments Katharine Barry, Inserm doctoral student at Sorbonne Université and first author of this research. However, the negative association observed among the mothers could suggest that a two-week period of paternity leave is on the other hand not sufficient to prevent postpartum depression in mothers. “

The scientists believe that this negative association among mothers could be due to the unequal distribution of time spent on childcare, selection bias, or both.

“Despite taking many possible confounding factors into account, we were unable to sufficiently evaluate the pre-existence of depressive disorders outside of another pregnancy in the mothers. It is therefore possible that those fathers whose partner is at greater risk of depression take paternity leave more readily, explains Melchior. However, our findings underscore the importance of family policies targeted at fathers in terms of the parents’ mental health, continues the researcher, as they can advance equality of the sexes in the labor market and increase the fathers’ participation in the family sphere. 

Future research should therefore examine the impact that the duration and timing of paternity leave may have on the mental health of parents and the development of children, including since this leave was extended in 2021.

 

[1] The French Longitudinal Study from Childhood (Elfe) is a national cohort of children followed from birth to adulthood to study the familial, economic and sociocultural factors that can influence the development of children.

[2] The average duration of paternity leave in the OECD countries in 2021. In France, paternity leave was introduced in 2002, and extended from 11 to 25 consecutive days in 2021.

[3] In this study, the participating fathers had up to 4 months after the birth of their child to take their paternity leave.

Trial on safety and immunogenicity of Ebola vaccines yields promising results

© Inserm/Patrick Delapierre, 2018

Ebola epidemics occur periodically in various sub-Saharan African countries. While vaccines exist and have already received WHO Prequalification[1] against the Zaire ebolavirus species, it is essential to pursue and intensify efforts to supplement the available data to develop a safe and effective Ebola vaccine strategies in adults and children alike. The PREVAC international consortium (see box), which includes scientists from Inserm and from institutions in Africa, USA and UK, has published the results of a large-scale randomized clinical trial in West Africa in the New England Journal of Medicine. These results confirm the safety of three different vaccine regimens, and suggest that an immune response is induced and maintained for up to 12 months.

In a context where many sub-Saharan African countries regularly face Ebola outbreaks, vaccines are seen as a central tool to fight the spread of the disease. Since 2019, two vaccines have obtained WHO Prequalification against the Zaire ebolavirus species: the vaccine rVSVΔG-ZEBOV-GP developed by Merck, Sharpe & Dohme, Corp., and the Ad26.ZEBOV and MVA-BN-Filo vaccine regimen from Johnson & Johnson.

Beyond these advances, research on Ebola vaccines must continue. Indeed, additional data is needed in order to establish the most appropriate recommendations regarding the use of these vaccines, in different categories of the population.

 

Three Vaccine Regimens Tested

This is the goal of the PREVAC international consortium. Starting in 2017, a vast, multicenter, randomized, placebo-controlled, phase 2 trial mobilized African, European and US research teams working together in Liberia, Guinea, Sierra Leone, and Mali.  It is one of the largest Ebola vaccination trials to date – conducted with both adults and children aged 1 year and older.

The trial aimed to measure the rapidity, intensity and durability of the immune responses generated by three different Ebola vaccine regimens, involving the vaccines mentioned above. It also evaluated the safety and tolerability of the various products administered.

 

  • The first vaccine regimen tested consisted of injecting one dose of ZEBOV followed 56 days later by one dose of MVA-BN-Filo.
  • The second regimen consisted of injecting one dose of rVSVΔG-ZEBOV-GP.
  • Finally, the third regimen started with one dose of rVSVΔG-ZEBOV-GP followed 56 days later with the same vaccine as a booster.

 

In total, the trial included 1400 adults and 1401 children between 1 and 17 years of age, who were randomized into several groups to test and compare the three regimens versus placebo.

The data obtained suggest that all three regimens are safe and well-tolerated in adults and children.  After vaccination and within the 7 days that followed, the majority of the participants reported pain at the injection site and other minor symptoms (fever, muscle and joint pain, headache, etc.), which generally disappeared after 7 days.

The three regimens also generated a rapid increase, after 14 days, of the amount of antibodies directed against the virus, with a peak at between 1 and 3 months after the first vaccination. While it’s not yet possible to say whether this immune response prevents infection, current scientific literature suggests a strong correlation between the amount of these antibodies and the level of protection against the virus. These antibodies were detected up to 12 months after the first injection.

“The data collected during this clinical trial are valuable because they help confirm the safety and potential efficacy of the available vaccines, making it possible to refine the vaccination recommendations during both Zaire ebolavirus epidemic and inter-epidemic periods, in populations at risk,” explains the trial’s principal investigator, Yazdan Yazdanpanah.

 

“This trial is marked by a high participant retention rate thanks to the unwavering involvement of all the professionals in the field, and the population’s adherence to the research that led to these results,” explains principal investigator Mark Kieh.

 

“The PREVAC trial is a real example of success for international research in emerging and re-emerging infections. We show that with solid collaboration founded on strong partnerships, we can advance Ebola research in the areas of the world most affected by the disease,” emphasizes H Clifford Lane, NIAID Deputy Director for Clinical Research and Special Projects.

 

The work of the PREVAC consortium in West Africa continues, thanks in part to a European funding from the EDCTP supported by the European Union. Participants will be followed up over a 5-year period to assess the long-term safety of vaccines and the durability of the immune response. It is crucial to obtain such data, which will shed light for example on whether or not it is necessary to provide a vaccine booster to individuals who are already vaccinated.

 

About PREVAC

Partnership for Research on Ebola Vaccinations (PREVAC) is an international consortium that conducts research in West Africa to assess the safety and efficacy of Ebola vaccination.

The project is co-funded by Inserm, NIAID, LSHTM, and COMAHS and is supported by Guinea, Liberia, Mali, and Sierra Leone. In-field support from the NGO ALIMA has also been crucial to foster the population’s adherence to the research and to monitor the volunteers. The companies Merck and JnJ provided the vaccines used in the trial.

The project received additional funding to continue monitoring volunteers over the long term (PREVAC-UP project) via the European and Developing Countries Clinical Trials Partnership (EDCTP2) program supported by the European Union.

 

PREVAC UP Partner Organizations:

Institut national de la santé et de la recherche médicale (Inserm)*, France; Centre National de Formation et de Recherche en Santé Rurale (CNFRSR)*, Guinea; Institut Bouisson Bertrand* (IBB)/ Centre de Recherche et de Formation en Infectiologie (CERFIG) France/ Guinea; London School of Hygiene & Tropical Medicine (LSHTM)*, United Kingdom; University of Sierra Leone, College of Medicine and Allied Health Sciences (COMAHS)*, Sierra Leone; Alliance for International Medical Action (ALIMA)*, France; Inserm-Transfert SA*, France; National Institute of Allergy and Infectious Diseases (NIAID), USA; Université des Sciences, des Techniques et des Technologies de Bamako (USTTB)*, Mali; Ministry of Health (Centre pour le Développement des Vaccins –Mali)*, Mali; National Public Health Institute of Liberia (NPHIL), Liberia

*EDCTP grant agreement signatories

Inserm’s participation in PREVAC is in part through a subcontract with Leidos Biomedical Research, Inc. which operates the Frederick National Laboratory for Cancer Research on behalf of the National Cancer Institute. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government.

The PREVAC UP project is funded by the European and Developing Countries Clinical Trials Partnership (EDCTP2) program supported by the European Union and the UK Department of Health & Social Care (Grant number RIA2017S – 2014 -PREVAC-UP). Besides the EDCTP2 grant, PREVAC-UP benefits from co-funding from Inserm, the NIAID, the LSHTM and the COMAHS as well as host country support from Liberia, Sierra Leone, Guinea and Mali.

[1] Prequalification means that a vaccine meets WHO standards of quality, safety, and efficacy. Based on this recommendation, United Nations agencies and Gavi, the Vaccine Alliance, can procure the vaccine for the countries where there is a high level of risk.

High Temperatures Have Short-Term Impact on All Major Causes of Death, Including Suicide

The findings of this study are based on records of all deaths having occurred in France over a 49-year period, compiled by the Inserm CépiDc. © Adobe Stock

Temperature and mortality are linked. There is a short-term increase in mortality when temperatures are at their hottest or coldest – a phenomenon known as a “U-shaped relationship”. Inserm researchers at the Institute for Advanced Biosciences (Inserm/Université Grenoble Alpes/CNRS) and the Inserm Epidemiology Center on Medical Causes of Death (CépiDc) have sought to determine the extent to which this relationship between temperature and mortality varies according to the medical cause of death; for what causes of death is the effect of hot temperatures the highest; and whether there are signs of adaptation to extreme temperatures – an important question in the context of climate change. This new study, based on all of the deaths having occurred in France over a 49-year period, confirms the U-shaped relationship (see Graph 1 below) observed between temperature and the majority of the causes of death considered. However, an exception has been observed for death from suicide, which rose steadily in line with the temperature, without the increased risk at cold temperatures observed for the other causes of death. Furthermore, the effect of temperatures at either extreme on all-cause mortality seems to have reduced slightly during this period, which could mean that our society is adapting better. This research has been published in the American Journal of Epidemiology.

Previous scientific publications have studied the short-term link between mortality (irrespective of cause) and temperature – with excess mortality documented during both the hottest and coldest periods, which corresponds to a U-shaped relationship.

For the first time, Inserm researchers at the Institute for Advanced Biosciences in Grenoble were able to study this phenomenon over a period of almost 50 years and rank the causes of death according to their sensitivity to heat. They based their study on the Inserm medical causes of death (CépiDc) registry, whose records date back to 1968. A total of 24.4 million deaths were recorded over 49 years, including over 502,000 by suicide.

The scientists cross-referenced the number of deaths occurring each day in each region along with daily temperatures throughout the study period. The approach[1] concerned only the short-term links between temperature and mortality, and not long-term trends in mortality or geographic variations in mortality.

“Here we are seeing just one of the last stages of a long and complex multifactorial causal chain leading to death,” explains study leader and Inserm research director, Rémy Slama.

 

Graph 1: Association between temperature (x-axis) and relative risk of all-cause mortality (y-axis) for the 1968-2016 period (U-shaped relationship)

When all deaths were considered simultaneously, the mortality rate was minimal when the temperature was close to 20°C, and crossed when the temperature either increased above or decreased below 20°C. Among the 22 causes of death considered, almost all followed this U-shaped relationship described in previous studies (see graph above).

Suicide mortality was a notable exception, with a steady increase in line with temperature – from the lowest temperatures to the highest (see graph below). Among the 22 causes of death considered, suicide was ranked seventh place in terms of sensitivity to heat.

Graph 2: Association between temperature and suicide mortality over the 1968-2016 period

As far as the link between heat and suicide is concerned, the strongest association was found with the temperature on the day of death (rather than that of the preceding days), signifying that it is a very short-term association.

Finally, among the 10 causes of death most strongly related to heat, four involved the nervous system (mental and behavioral disorders, nervous system diseases, cerebrovascular diseases, and suicide). This suggests substantial nervous system sensitivity to high temperatures.

“In order to explore these findings in greater depth, it would be interesting to study the biological parameters that would enable us to understand the underlying mechanisms behind this link between temperature and suicide,” explains Slama.

“The existing hypotheses include at least two non-exclusive avenues: one being the changes in social relationships when temperatures are very high, which could influence suicide; the other being an alteration in endocrine and nervous system functioning in the event of extreme heat, which could increase the risk of suicide, he continues. Research shows that levels of the hormone serotonin tend to decrease when temperatures are high. However, lower levels of this neurotransmitter, which is involved in regulating mood and anxiety, could play a role in the decision to commit suicide,” concludes the research director.

Tendency of French society to adapt to extreme temperatures

The relative wealth of data offered by the registry of the causes of death also made it possible to study the question of adaptation to extreme temperatures. By dividing the study period into three, the scientists were able to study whether the effect of temperatures varied between these periods.

The effects of temperature on all-cause mortality and suicide mortality were attenuated between the 1968-1984 and 1985-2000 periods: for a given temperature, the risk of death was lower during the 1985-2000 period than during the 1968-1984 period. This was seen both for hot temperatures above 20°C and cold temperatures of around 0°C. However, no further attenuation was observed during the 2001-2016 period compared to the previous period (1985-2000).

These findings show the tendency of French society to adjust to extreme temperatures – hot and probably also cold – at the end of the 20th century.

“Although it was not the objective of the study to explain the drivers of this adaptation, we can hypothesize that it is essentially societal, involving improvements to housing and the health system rather than the result of biological evolution, which in principle is very slow,” explains Slama.

The short-term association between temperature and suicide risk could be taken into account in prevention campaigns related to the effects of heat and suicide. It also raises the question of the expected impact of climate change on mortality, which particularly depends on the relationship between temperature and mortality and the ability of societies to adapt to extreme temperatures.

[1] Known as a “time series” analysis

 

If you are having suicidal thoughts, call 3114. The national suicide prevention number is open 24/7. Free and confidential, professionals are there to listen to you.

fermer