Obstructive sleep apnea (OSA) is a chronic condition characterized by recurrent pauses in breathing caused by the collapse of the upper airways, which results in intermittent hypoxia and arousals during the night. The disorder is associated with a vast number of comorbidities affecting different systems, including cardiovascular, metabolic, psychiatric, and neurological complications. Due to abnormal sleep architecture, OSA patients are at high risk of circadian clock disruption, as has been reported in several recent studies. The circadian clock affects almost all daily behavioral patterns, as well as a plethora of physiological processes, and might be one of the key factors contributing to OSA complications. An intricate interaction between the circadian clock and hypoxia may further affect these processes, which has a strong foundation on the molecular level. Recent studies revealed an interaction between hypoxia-inducible factor 1 (HIF-1), a key regulator of oxygen metabolism, and elements of circadian clocks. This relationship has a strong base in the structure of involved elements, as HIF-1 as well as PER, CLOCK, and BMAL, belong to the same Per-Arnt-Sim domain family. Therefore, this review summarizes the available knowledge on the molecular mechanism of circadian clock disruption and its influence on the development and progression of OSA comorbidities.
Objective: C-reactive protein (CRP) is the major acute-phase plasma protein. Studies show that patients with various mental disorders have elevated levels of CRP. The aim of the study was to determine differences in CRP serum level in patients with acute schizophrenia, unipolar depression, bipolar depression and bipolar mania. Method: Serum level of CRP was measured in 950 Caucasian inpatients (589 women, 62.0%; mean age 50.3 years). Results: Mean concentration of CRP in study groups was: schizophrenia (n = 485) 5.30 mg/l, unipolar depression (n = 319) 5.61 mg/l, bipolar disorder (n = 146) 4.65 mg/l, bipolar depression (n = 114) 3.82 mg/l and bipolar mania (n = 32) 7.36 mg/l. There was no difference for CRP levels between patients with schizophrenia, unipolar depression, bipolar depression and bipolar mania (P = 0.58). The overall rate of being above the high level of CRP (set at 3.0 mg/l) was 35.7% for schizophrenia, 38.6% for unipolar depression, 40.4% for bipolar disorder, 40.4% for bipolar depression and 40.6% for bipolar mania. There were no significant differences in the risk of having high level of CRP between the clinical groups. The rate of patients being above high level was higher in women. We also found that in whole study group CRP level was positively correlated with age (P = 0.002). Conclusions: Although there is no statistically significant difference in CRP serum level between patients with schizophrenia, unipolar depression, bipolar depression and bipolar mania, our results show that more than one-third (37.4%) of all subjects had CRP level > 3 mg/l, which is the cut-off point for high cardiovascular risk.
Glutamate and γ-aminobutyric acid (GABA) are the two main neurotransmitters in the human brain. The balance between their excitatory and inhibitory functions is crucial for maintaining the brain’s physiological functions. Disturbance of glutamatergic or GABAergic neurotransmission leads to serious health problems including neurodegeneration, affective and sleep disorders. Both GABA and glutamate are involved in the control of the sleep–wake cycle. The disturbances in their function may cause sleep and sleep-related disorders. Obstructive sleep apnea (OSA) is the most common sleep respiratory disorder and is characterized by repetitive collapse of the upper airway resulting in intermittent hypoxia and sleep fragmentation. The complex pathophysiology of OSA is the basis of the development of numerous comorbid diseases. There is emerging evidence that GABA and glutamate disturbances may be involved in the pathogenesis of OSA, as well as its comorbidities. Additionally, the GABA/glutamate targeted pharmacotherapy may also influence the course of OSA, which is important in the implementation of wildly used drugs including benzodiazepines, anesthetics, and gabapentinoids. In this review, we summarize current knowledge on the influence of disturbances in glutamatergic and GABAergic neurotransmission on obstructive sleep apnea.
Sleep deficiency and insomnia deteriorate the quality of patients’ lives, yet the exact influence of these factors on the immune system has only begun to gain interest in recent years. Growing evidence shows that insomnia is a risk factor for numerous diseases, including common infections and autoimmune diseases. Levels of inflammatory markers also seem to be abnormal in sleep deficient individuals, which may lead to low-grade inflammation. The interpretation of studies is difficult due to the equivocal term “sleep disturbances,” as well as due to the various criteria used in studies. This narrative review aims to summarize the available knowledge regarding the bidirectional influence of the immune system and sleep disturbances.
Obstructive sleep apnea (OSA) is chronic disorder which is characterized by recurrent pauses of breathing during sleep which leads to hypoxia and its two main pathological sequelae: oxidative stress and chronic inflammation. Both are also associated with cellular senescence. As OSA patients present with higher prevalence of age-related disorders, such as atrial hypertension or diabetes mellitus type 2, a relationship between OSA and accelerated aging is observable. Furthermore, it has been established that these OSA are associated with telomere shortening. This process in OSA is likely caused by increased oxidative DNA damage due to increased reactive oxygen species levels, DNA repair disruptions, hypoxia, chronic inflammation, and circadian clock disturbances. The aim of the review is to summarize study outcomes on changes in leukocyte telomere length (LTL) in OSA patients and describe possible molecular mechanisms which connect cellular senescence and the pathophysiology of OSA. The majority of OSA patients are characterized by LTL attrition due to oxidative stress, hypoxia and inflammation, which make a kind of positive feedback loop, and circadian clock disturbance.