Obstructive sleep apnea (OSA) is a chronic condition characterized by repetitive collapse of the upper airway during sleep, leading to intermittent hypoxia (IH) and recurrent arousals from sleep. It is a prevalent disorder, with considerable morbidity and mortality and various studies indicating a causal relationship between OSA and hypertension, cardiovascular disease, insulin resistance, diabetes mellitus, neurocognitive dysfunction and chronic mental diseases. Accumulated evidence suggests that OSA is the consequence of underlying biological, metabolic and neurologic dysregulation, through low-grade inflammation, oxidative and nitrosative stress, and neurotransmitter imbalances, respectively. Each individual can express multiple disease states according to the underlying biological dysregulation. OSA is a very common comorbidity among psychiatric patients. Both OSA and chronic mental illness share similar complaints, like tiredness, lack of energy, concentration problems, sleepiness or hypersomnolence, and insomnia. Moreover, psychiatric disorders have independent associations with obesity, metabolic dysfunction, and cardiovascular disease, which are all independent predictors of OSA. Furthermore, anxiety and depression are very prevalent in sleep apneic patients.
As the exact underlying pathophysiological mechanisms are still unclear, in this Research Topic, we aim to identify possible interactions between OSA, IH, and / or sleep fragmentation and psychological stress and neuropsychological disturbances. The “chronic intermittent hypoxia” (CIH) theory has become increasingly popular as it accounts for the biological, metabolic, and neurologic dysregulation that underpins OSA. CIH exposure promotes increased tonic and reactive afferent chemoreceptor outputs from the carotid body compared with normoxia, probably via increased local ROS production, which leads to increased synthesis and release of catecholamines. Increased levels of circulating catecholamines and cortisol and impairment of the hypothalamic-pituitary-adrenal (HPA) axis function may induce psychological stress and may participate in the development of cardiometabolic diseases and neuropsychological disturbances. In psychiatric populations who already experience dysregulation of mood and possible neurocognitive deficits, it is likely that the same degree of hypoxic insult and sleep fragmentation may result in greater decompensation of the psychiatric disorder. Moreover, maintaining stable sleep-wake cycles is also crucial in maintaining stability in these patients and repetitive arousals and sleep fragmentation can lead to instability and acute deterioration. On the other hand, the sympathetic hyperarousal observed in psychiatric disorders and resultant sleep fragmentation, may lead to instability of upper airways and apneas during sleep. Moreover, the administration of sedative drugs further aggravates metabolic syndrome and airway resistance, which in turn stimulate underlying pathophysiological mechanisms leading to OSA.
It appears to be a vicious cycle between biological, metabolic and neurologic dysregulation in OSA. However, the underlying pathophysiological pathways still are not clear and future studies need to be conducted to better ascertain these relationships. In this Research Topic we welcome contributions in OSA patients addressing these underlying pathopysiological pathways, and studies relating to the following are of especial interest:
1) What stimulates the onset of OSA and the cascade of biological, metabolic and neurologic events?
2) Does genetic or epigenetic susceptibility to OSA influence the progression to different disease states; e.g cardiometabolic, neuropsychological, or both?
3) How do different clinical OSA phenotypes (i.e. sleepy or insomniac patient) lead to different metabolic and neurologic dysregulations?
4) How do different underlying pathophysiological phenotypes of OSA, anatomical or non-anatomical factors, like impairment in pharyngeal dilator muscle control and function during sleep, increased propensity for awakening during airway narrowing (low respiratory arousal threshold) and respiratory control instability (high loop gain), lead to different diseases?
5) Are the effects of intermittent hypoxia and sleep fragmentation combined, or does each have a mechanism that stimulates different pathways?
6) What are the long-term effects of end-organ morbidities, e.g. liver, pancreas, brain etc?
7) What is the impact of therapy? Why do comorbidities still exist despite the fact apneas / hypopneas / oxygen desaturations / arousals, comorbidity are routinely corrected?
Obstructive sleep apnea (OSA) is a chronic condition characterized by repetitive collapse of the upper airway during sleep, leading to intermittent hypoxia (IH) and recurrent arousals from sleep. It is a prevalent disorder, with considerable morbidity and mortality and various studies indicating a causal relationship between OSA and hypertension, cardiovascular disease, insulin resistance, diabetes mellitus, neurocognitive dysfunction and chronic mental diseases. Accumulated evidence suggests that OSA is the consequence of underlying biological, metabolic and neurologic dysregulation, through low-grade inflammation, oxidative and nitrosative stress, and neurotransmitter imbalances, respectively. Each individual can express multiple disease states according to the underlying biological dysregulation. OSA is a very common comorbidity among psychiatric patients. Both OSA and chronic mental illness share similar complaints, like tiredness, lack of energy, concentration problems, sleepiness or hypersomnolence, and insomnia. Moreover, psychiatric disorders have independent associations with obesity, metabolic dysfunction, and cardiovascular disease, which are all independent predictors of OSA. Furthermore, anxiety and depression are very prevalent in sleep apneic patients.
As the exact underlying pathophysiological mechanisms are still unclear, in this Research Topic, we aim to identify possible interactions between OSA, IH, and / or sleep fragmentation and psychological stress and neuropsychological disturbances. The “chronic intermittent hypoxia” (CIH) theory has become increasingly popular as it accounts for the biological, metabolic, and neurologic dysregulation that underpins OSA. CIH exposure promotes increased tonic and reactive afferent chemoreceptor outputs from the carotid body compared with normoxia, probably via increased local ROS production, which leads to increased synthesis and release of catecholamines. Increased levels of circulating catecholamines and cortisol and impairment of the hypothalamic-pituitary-adrenal (HPA) axis function may induce psychological stress and may participate in the development of cardiometabolic diseases and neuropsychological disturbances. In psychiatric populations who already experience dysregulation of mood and possible neurocognitive deficits, it is likely that the same degree of hypoxic insult and sleep fragmentation may result in greater decompensation of the psychiatric disorder. Moreover, maintaining stable sleep-wake cycles is also crucial in maintaining stability in these patients and repetitive arousals and sleep fragmentation can lead to instability and acute deterioration. On the other hand, the sympathetic hyperarousal observed in psychiatric disorders and resultant sleep fragmentation, may lead to instability of upper airways and apneas during sleep. Moreover, the administration of sedative drugs further aggravates metabolic syndrome and airway resistance, which in turn stimulate underlying pathophysiological mechanisms leading to OSA.
It appears to be a vicious cycle between biological, metabolic and neurologic dysregulation in OSA. However, the underlying pathophysiological pathways still are not clear and future studies need to be conducted to better ascertain these relationships. In this Research Topic we welcome contributions in OSA patients addressing these underlying pathopysiological pathways, and studies relating to the following are of especial interest:
1) What stimulates the onset of OSA and the cascade of biological, metabolic and neurologic events?
2) Does genetic or epigenetic susceptibility to OSA influence the progression to different disease states; e.g cardiometabolic, neuropsychological, or both?
3) How do different clinical OSA phenotypes (i.e. sleepy or insomniac patient) lead to different metabolic and neurologic dysregulations?
4) How do different underlying pathophysiological phenotypes of OSA, anatomical or non-anatomical factors, like impairment in pharyngeal dilator muscle control and function during sleep, increased propensity for awakening during airway narrowing (low respiratory arousal threshold) and respiratory control instability (high loop gain), lead to different diseases?
5) Are the effects of intermittent hypoxia and sleep fragmentation combined, or does each have a mechanism that stimulates different pathways?
6) What are the long-term effects of end-organ morbidities, e.g. liver, pancreas, brain etc?
7) What is the impact of therapy? Why do comorbidities still exist despite the fact apneas / hypopneas / oxygen desaturations / arousals, comorbidity are routinely corrected?
