Department of Sport, Exercise and Health

Phases of immobilization are accompanied by a loss of muscle strength. Initial data show that these losses are i) greater in older men than in young men and ii) greater in young women than in young men. The project now aims to investigate why the different effects occur and how a period of re-training affects these losses.

Content and objectives of the research project

Immobilization results in a decline in physical function, even over short durations. This decline can hinder everyday activities, such as walking, particularly in seniors experiencing age-related physical deterioration. Preliminary findings suggest that the impact of immobilization and the recovery process varies by age and gender. Specifically, (i) young women appear to be more affected than young men, and (ii) older men show greater performance losses compared to their younger counterparts. The underlying reasons for these disparities remain uncertain.

This study therefore aims to explore the underlying mechanisms that can explain the age- and gender-specific differences. Four groups - young men, young women, older men, and older women - will participate in a 10-day immobilization of one leg, followed by three weeks of rehabilitation training. The investigation will focus on physical functions such as strength, balance, and gait, as well as the mechanisms underlying potential differences between groups. Advanced research methods will be employed to assess muscle activity, the interplay between the nervous system and muscles, and tendon properties.

Scientific and social context of the research project

This study aims to shed light on how immobilization and re-training affect different groups, which is important in view of the ageing world population. The inclusion of different genders is fundamental, as it is not possible to draw conclusions from studies with a specific group (e.g. young men) to the population as a whole. For example, there is currently no data on immobilization effects in old women, which this study will change.

Premature birth, defined as the delivery of babies before the 37th week of pregnancy, presents an increasing challenge. Since the 1980s, medical advances such as specialized medication and ventilation techniques have significantly improved the survival rates of premature infants. Globally, approximately 11% of all births are premature, with Switzerland reporting about 5700 premature newborns each year.

Prematurity increases the risk of cardiovascular disease. Research indicates that very premature babies face a notably higher risk of heart problems. These infants often exhibit different heart shapes and functions, along with elevated blood pressure, beginning in infancy and potentially persisting into adulthood. This is partly because their blood vessels tend to be less elastic.

In addition to cardiovascular issues, premature babies frequently encounter challenges with certain cognitive tasks. Traditionally, the cardiovascular and brain functions of premature infants have been studied separately, despite the known close link between these systems in adults. Therefore, the EXCELSIOR study is exploring the impact of exercise on the small blood vessels in the eye, which can be examined through retinal vessel imaging. The objective is to determine if positive changes in these blood vessels correlate with improved cognitive performance.

Overnutrition, reduced energy expenditure and chronic inflammation stimulate triglyceride storage. Once the triglyceride stores are saturated, lipids in excess are redirected to form sphingolipids. However, sphingolipid accumulation drives complex molecular alterations, which promote peripheral insulin resistance and atherosclerosis. Failure to manage this sphingolipid overload eventually results in diabetes mellitus and coronary artery diseases. In the last decade, these pathophysiological findings found resonance in milestone clinical studies. In primary prevention, a score combining the blood level of four sphingolipids outperformed the 2019 SCORE of the European Society of Cardiology in terms of cardiovascular risk prediction. The same score predicted cardiovascular mortality beyond low-density lipoprotein cholesterol in secondary prevention. Remarkably, sphingolipids are not limited to cardiovascular risk prediction, as they were shown to predict diabetes mellitus onset ten years before the disease was diagnosed. While the utility of sphingolipid profiling to stratify cardiometabolic risk is well-established, little is known about therapeutic modalities to lower sphingolipid levels. If circulating sphingolipids are to be measured in clinical practice, providing patients with evidence-based sphingolipid-lowering interventions is essential. As exercise is a powerful means to prevent and treat cardiometabolic diseases, exercise interventions are ideal candidates for mitigating sphingolipid levels in a cost-effective, safe, and patient-empowering manner. This 2-arm, monocentric, randomised controlled trial explores whether and to what extent an 8-week fitness-enhancing training programme can lower serum sphingolipid levels of middle-aged adults at elevated cardiometabolic risk (n= 98, 50% females). The exercise intervention will consist of supervised high-intensity interval training (three sessions weekly), while the control group will receive physical activity counselling based on current guidelines. Maximal cardiopulmonary exercise tests will be performed before and after the 8-week programme to verify patients' fitness has improved. Blood will be sampled early in the morning in a fasted state before and after the 8-week programme. Participants will be provided with individualised, pre-packaged meals for the two days preceding blood sampling to minimise potential confounding. An 'omic-scale sphingolipid profiling, using high-coverage reversed-phase liquid chromatography coupled to tandem mass spectrometry, will be applied to capture the circulating sphingolipidome. Classical biomarkers of cardiometabolic health (total cholesterol, low- and high-density density lipoprotein cholesterol, triglycerides, glycated haemoglobin, and the homeostatic model assessment for insulin resistance) and retinal vessel diameters, a novel surrogate of microvascular health, will also be assessed pre-and post-intervention. This study will inform clinicians whether and to what extent exercise can be used as an evidence-based treatment to lower circulating sphingolipid levels.

Background and rationale.

Mental health disorders are the leading cause of disability in adolescents worldwide. 70 to 80% of individuals with mental disorders experience sleep disturbances. Preliminary evidence from adult studies suggest that treating sleep disturbances in these patients can improve mental health outcomes. Moreover, regular physical activity (PA) is increasingly promoted as a remedy for sleep and other mental health problems. Thus, combining sleep therapy and PA counseling may synergistically improve mental health outcomes in adolescent psychiatric patients. Guidance on how to address sleep disturbances and PA counselling among this population in routine clinical care has the potential to improve clinical and psychosocial outcomes.

Overall objectives.

To improve psychopathology in adolescent psychiatric outpatients with comorbid sleep disturbances by testing a novel behavioral intervention (SLEEPAC) that improves both sleep and PA levels. This multi-component intervention combines CBT-I, circadian treatment, and PA counseling and will be compared against treatment as usual (TAU).

Specific aims.

With the prospect of further developing and fine-tuning transdiagnostic treatment protocols for young psychiatric patients with comorbid sleep disturbances, the objectives of the proposed study are twofold: (1) To test the efficacy of a novel transdiagnostic blended care e-health sleep (CBT-I + circadian treatment) and PA therapy and to test its efficacy against TAU. The primary endpoint is severity reduction of psychopathology. Improvements of sleep health and regular PA levels will be investigated as secondary outcomes. (2) To evaluate the prognostic value of sleep neurophysiological biomarkers (high-density sleep-EEG) on intervention efficiency, thereby advancing current approaches in precision psychiatry.

Methods.

The proposed study will recruit 140 psychiatric outpatients with comorbid sleep problems from our partner clinics in Basel and Bern (KJP-UPD Bern, UKBB Basel). Inclusion criteria: aged 13-18 years, presence of sleep problems in addition to a psychiatric diagnosis. Adolescents will be serially randomized over 1,5 years into one of 2 intervention arms: (a) SLEEPAC; or (b) TAU. The intervention will be delivered in 6 sessions over 12 weeks. Data will be collected at 3 time points: Baseline, post-intervention, and 6-months follow-up. Psychopathological load will be assessed via Symptom Checklist-90-Revised. The composite sleep health score is based on self-reported sleep quality, -quantity, and timing, complemented by 7-day sleep tracker (Oura Ring Gen3). PA will be assessed objectively via the same device (Oura Ring was selected due to prior compliance issues among this population with Actigraph). Primary biomarkers are the micro-architectural features of sleep assessed by a high-density sleep-EEG, such as sleep spindles, slow wave activity, and REM-latency. Secondary biomarkers include heart rate variability, and fitness.

Expected results.

The proposed study aims to further develop and fine-tune transdiagnostic treatment protocols (i.e. for multiple psychiatric disorders) in adolescent psychiatric outpatients with sleep disturbances. Testing the potential of sleep treatments for improving psychopathology in young psychiatric patients is a promising and highly novel approach. Thus, it is expected that both SLEEPAC and TAU will improve psychopathology in youth, with SLEEPAC resulting in superior effects than TAU alone.

Impact. The onset of mental health disorders is often during adolescence, requiring countermeasures at an early developmental stage. Since sleep disturbances are a diagnostic feature for many psychiatric disorders, treating sleep problems transdiagnostically may positively impact other health outcomes. PA counseling may complement the benefits of the sleep intervention, working in concert to improve mental health outcomes.