Chronic psychosocial stress: A primary driver of sleep apnea onset in rats and humans
- Marianne Gagnon
- Stéphanie Fournier
- Émilie Gobeil
- Marie-Pier Bouchard
- Loralie Mei Guay
- François Marcouiller
- Vincent Joseph
- Natalie J. Michael
- Benoit J. Arsenault
- Richard Kinkead
2026-08-17
Poor sleep quality and chronic psychosocial stress are interrelated risk factors for hypertension, metabolic disease, and neuropsychiatric disorders. Sleep apnea (SA) is a respiratory disorder that disrupts sleep, affecting ~1 billion adults worldwide. However, the origins of SA remain incompletely understood. Clinically, activation of the stress pathways is often considered a consequence of SA rather than a causal factor. Here, we combined preclinical experiments with Mendelian randomization (MR) analysis to show that chronic psychosocial stress is a primary driver of SA onset. In adult rats, 3 wk of social isolation (SI; single housing) activated the stress response, augmented apneas during natural sleep, and increased the ventilatory responses to O 2 and CO 2 challenges. In supine anesthetized rats, obstructive apneas with O 2 desaturations were 5 times more frequent in SI males than in controls, with no effect in females. SI-related anomalies in airway motor control contribute to the problem. SI also induced increased blood pressure and augmented fat gain, especially in males. In humans, MR analysis using genome-wide association studies of multiple stress-related neurological disorders from European cohorts (~100,000 to 1,096,458 participants) revealed significant effects of loneliness on the risk of SA, independent of adiposity. Together, these results challenge the conventional view of stress as merely a consequence of SA and instead position it as a possible cause. These results open the door to a paradigm shift, recognizing psychosocial stress as a risk factor paves the way for alternative avenues in basic mechanistic research, as well as in preventive and therapeutic strategies.