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 per 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 apnoeic 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, and 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. (Figure presented.).