On the origins of sleep disordered breathing, cardiorespiratory, and metabolic dysfunction: Which came first, the chicken or the egg?

Sleep disordered breathing (SDB) is a complex, sex specific, and highly heterogeneous group of respiratory disorders. Nevertheless, sleep fragmentation and repeated fluctuations of arterial blood gases for several hours/night are at the core of the problem; together, they impose significant stress to the organism with deleterious consequences on physical and mental health. SDB increases the risk of obesity, diabetes, depression and anxiety disorders; however, the same health issues are risk factors for SDB. So, which came first, the chicken or the egg? What causes the appearance of the first significant apneic events during sleep? These are important questions because although moderate to severe SDB affects ∼500 million adults globally, we still have a poor understanding of the origins of the disease, the main treatments (and animal models) focus on the symptoms rather than the cause. Because obesity, metabolic dysfunction, and stress-related neurological disorders generally appear progressively, we discuss how the development of these diseases can lead to specific anatomical and non-anatomical traits of SDB in males and females while considering the impacts of sex steroids. In light of the growing evidence indicating that the carotid bodies are important sensors of key metabolic and endocrine signals associated with stress and dysmetabolism, we propose that these organs play a key role in the process. Abstract figure legend Sleep disordered breathing (SDB) is a complex, multifactorial respiratory disorder with significant sex-based differences. Despite its growing prevalence and societal impact, our understanding of the origins of SDB remains limited. This schematic representation proposes a timeline of pathophysiological disturbances leading to SDB. It illustrates how stress-related neurological disorders, diabetes, and obesity interact to contribute to the emergence of respiratory dysfunction during sleep. We proposed that sensing of key metabolic and endocrine signals associated with stress and dysmetabolism by the carotid bodies are key to the process. Age-related decline in sex-steroids contribute to the problem. This article is protected by copyright. All rights reserved.