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Reactions to study linking sleep deprivation in adolescence with increased risk of multiple sclerosis

A Swedish study has found an association between lack of sleep or poor quality sleep during adolescence and an increased risk of developing multiple sclerosis later in life. They put the relative increased risk at 40 %. The results are published in the Journal of Neurology, Neurosurgery and Psychiatry.

24/01/2023 - 00:30 CET
Expert reactions

Pablo Villoslada - sueño esclerosis EN

Pablo Villoslada

Head of the neurology service and director of the neurosciences programme, Hospital del Mar

Formerly Neuroinmunology group leader at IDIBAPS – Hospital Clínic and adjunct professor at Stanford University

Science Media Centre Spain

The Karolinska Institute group has been working for years on the epidemiology of multiple sclerosis and they do very rigorous studies, as in this case. 

Until now there was no clear evidence that lack of sleep in adolescents was a risk factor. Of course, it is well known that with adolescence the sleep pattern changes and that most adolescents are sleep deprived, but this does not necessarily increase the risk of MS. In this study they show that sleeping less than seven hours slightly increases that risk. As they say, this does not mean that this is the cause, it could be the consequence of already incubating the disease (called the prodrome of the disease in medicine).  

These results help to design public health policies, promoting healthy sleep in adolescents. For people who already have the disease, improving their sleep will help improve their overall health, although it probably won't change how their disease progresses. 

As to how sleep deprivation might cause an increased risk of multiple sclerosis, it could be due to down-regulation of the immune response due to the chronic stress of sleep deprivation. All physiological functions such as sleep and immune response are closely related to each other. 

Like any epidemiological study, it has the limitations that the population studied is limited and that, as the risk factor cannot be changed during the study, in this case lack of sleep, it cannot be established whether this factor is a cause or a consequence or just another factor. Data collection is based on questionnaires and these are always subject to recall and perception biases, even more so in this population so susceptible to social influences. The study is well controlled for confounders such as age, sex, ethnicity, smoking, history of infectious mononucleosis and sun exposure (which determines vitamin D levels, which are very low in Sweden and a risk factor for multiple sclerosis). In a second analysis they adjusted for obesity, a risk factor for poor sleep.

The author has not responded to our request to declare conflicts of interest

Luis Querol - sueño esclerosis EN

Luis Querol

Neurologist in the Neuromuscular Diseases Unit - Autoimmune Neurology - Neuromuscular Lab
Hospital de la Santa Creu i Sant Pau & Institut de Recerca Biomèdica Sant Pau, Barcelona

Science Media Centre Spain

This is a case-control study which, although methodologically sound, involves a design that is vulnerable to different biases, such as selection bias. Although it is a population-based study, the percentage of patients with multiple sclerosis (MS) from all over the country who decided to participate and answer the questionnaires that collected the information retrospectively is not recorded. On the other hand, the fact that information on sleep quality from years ago was collected retrospectively is subject to bias for several reasons: first and foremost, patients may provide answers influenced by their current sleep quality or mood, and secondly, even if the diagnosis of MS was made years later, some of the symptoms of the disease, which could include fatigue or sleep quality, may even be considered prodromal. 

Some of the confounding factors are very difficult to control. One aspect that could have been considered is whether the presence of current symptoms that influence the ability to respond negatively correlated with the number of previous hours of sleep reported. In other words, if someone is tired, depressed or very disabled now they may tend to see their quality of life in general, and also their sleep in particular, as worse than it actually was at the time. Looking at these correlations with scales of depression, fatigue or disability might have been interesting in order to rule out a role for these factors. 

This is a study that points to a possible risk factor with some relatively clear methodological limitations, as previously mentioned, and detects a relatively minor magnitude of effect of the risk factor when considering the magnitude of effect of other factors, such as Epstein-Barr virus infection. This makes the practical implications for the day-to-day management of the disease minor, although it may be an interesting idea to explore in future cohort studies. On the other hand, concrete implications would include the need to ensure good quality sleep for children and adolescents, which is a general health recommendation that should in any case be followed regardless of its influence on MS.

Luis Querol has received research funding from the Instituto de Salud Carlos III - Ministerio de Sanidad (Spain), CIBERER, GBS-CIDP Foundation International, Fundació la Marató de TV3, Roche, Merck, UCB and Grifols. He has provided expert advice to CSL Behring, Novartis, Sanofi-Genzyme, Merck, Annexon, Alnylam, Biogen, Janssen, Lundbeck, ArgenX, UCB, LFB, Octapharma and Roche. He is principal investigator of UCB's CIDP01/CIDP04 trial and is a member of the advisory committees of Sanofi Genzyme's clinical trials in CIDP and Roche's clinical trials in autoimmune neuropathies.


Celia Oreja-Guevara - sueño esclerosis EN

Celia Oreja-Guevara

Head of the Neurology Section and coordinator of the Multiple Sclerosis Unit at the Hospital Clínico San Carlos.

Science Media Centre Spain

Multiple sclerosis is an autoimmune disease that mainly affects young women. The cause of multiple sclerosis is as yet unknown. However, there are a number of risk factors that influence the onset of the disease, such as Epstein Barr virus infection, obesity in young people, low vitamin D, poor diet, etc. In addition, shift work does play a role in the disease. 

Other studies of neurological diseases such as cognitive impairment have found a link between sleep deprivation and poor sleep quality and the risk of neurodegenerative diseases. 

This study looks at other factors that may influence the onset of this disease, such as too little sleep and poor quality sleep. The overall study is well done and is based on the Swedish registry, which has good quality data. As they say, the limitations are that they have not been able to rule out other factors such as stress and dietary habits. 

It is a very interesting study and will need to be replicated in other populations, as this is a Swedish study only. 

The study concludes that insufficient sleep of less than seven hours and of poor quality during adolescence increases the risk of developing multiple sclerosis. Another important point is that a shift in sleep hours between weekdays and weekends does not influence the disease. 

The study provides an important new risk factor, because it is a preventable and avoidable factor. Adolescents could be educated to sleep at least seven hours and not to reduce their sleep hours by using social networks, among other things. 

In general, I think it is an interesting study that needs to be replicated in other populations, very well done, based on a national registry and that, if confirmed, can help to avoid this factor and therefore reduce the risk of developing multiple sclerosis.

The author has declared they have no conflicts of interest

Caminero - Esclerosis sueño (EN)

Ana Belén Caminero

Coordinator of the GEEMENIR group (Study Group on Multiple Sclerosis and Related Neuroimmunological Diseases ) of the Spanish Society of Neurology and head of the Neurology Section of the Ávila Health Care Complex

Science Media Centre Spain

This is a retrospective retrospective observational epidemiological case-control study that assesses the relationship between exposure or risk factors (short sleep duration and poor sleep quality at ages 15-19 years) and the subsequent development of Multiple Sclerosis (MS). The result is expressed in OR ('odds ratio'), which indicates how much more frequent the exposure to the risk factor was in the cases (MS patients) than in the controls (general population from the same geographical area, Sweden in this case, and of the same age, sex and residential area).  

The OR in this study is 1.4, which means that exposure to these factors (insufficient and poor quality sleep) increases the risk of MS by 40% compared to no exposure. The study design is of good quality with a reliable source of information, as well as the definition of cases and the selection of controls, but with the limitations inherent to this type of study: risk of bias, i.e. systematic errors in the assessment of the results (selection bias, information bias, recall bias). This type of study does not make it possible to establish a causal relationship between the exposure factor(s) (insufficient and poor quality sleep) and the development of the disease (MS), but it does make it possible to establish an association or dependency link between these factors and the development of the disease (MS). The article itself refers to the risk of the aforementioned biases, indicating that they have been minimised and partially controlled, and even to the possibility of reverse causality, i.e. that it is the disease (MS) that causes a quantitative and qualitative sleep deficiency. 

Despite these biases, there is biological plausibility that insufficient and poor quality sleep may increase the risk of MS and contribute along with other known environmental factors (smoking, history of infectious mononucleosis, sun exposure, serum vitamin D levels, adolescent body mass index) to its development. In this disease, it is believed that the set of environmental factors involved (some known and many not yet known) act in an individual genetically predisposed to the development of this disease. There is already evidence in line with this study that shift work, which also affects sleep and circadian rhythms, may increase the risk of MS (Norwegian study), as well as evidence that insufficient and poor quality sleep leads to a series of cellular and molecular changes that alter immune homeostasis and melatonin secretion, all of which have an impact on the development of chronic inflammatory diseases. 

Knowing about this new potential (partially) modifiable environmental risk factor is important to educate the adolescent population in the development of healthy lifestyle habits, including getting enough sleep each day, and trying to ensure that sleep is of good quality and restorative, in order to prevent the development of diseases such as MS. Adolescents and the general public should also be aware that compensating for sleep on holidays or on certain days of the week does not reverse the immune changes that lead to the disease, and therefore oversleeping on other days does not change this risk. Good quality and quantity of sleep is necessary for our immune system to function properly.


The author has declared they have no conflicts of interest
Insufficient sleep during adolescence and risk of multiple sclerosis: results from a Swedish case-control study
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  • Observational study
  • People
Journal of Neurology Neurosurgery & Psychiatry
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Åkerstedt et al.

Study types:
  • Research article
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  • Observational study
  • People
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