Neurotrophins in the Neuropathophysiology, Course, and Complications of Obstructive Sleep Apnea—A Narrative Review

Obstructive sleep apnea (OSA) is a disorder characterized by chronic intermittent hypoxia and sleep fragmentation due to recurring airway collapse during sleep. It is highly prevalent in modern societies, and due to its pleiotropic influence on the organism and numerous sequelae, it burdens patients and physicians. Neurotrophins (NTs), proteins that modulate the functioning and development of the central nervous system, such as brain-derived neurotrophic factor (BDNF), have been associated with OSA, primarily due to their probable involvement in offsetting the decline in cognitive functions which accompanies OSA. However, NTs influence multiple aspects of biological functioning, such as immunity. Thus, extensive evaluation of their role in OSA might enlighten the mechanism behind some of its elusive features, such as the increased risk of developing an immune-mediated disease or the association of OSA with cardiovascular diseases. In this review, we examine the interactions between NTs and OSA and discuss their contribution to OSA pathophysiology, complications, as well as comorbidities

Neurotrophins in the Neuropathophysiology, Course, and Complications of Obstructive Sleep Apnea—A Narrative Review

Obstructive sleep apnea (OSA) is a disorder characterized by chronic intermittent hypoxia and sleep fragmentation due to recurring airway collapse during sleep. It is highly prevalent in modern societies, and due to its pleiotropic influence on the organism and numerous sequelae, it burdens patients and physicians. Neurotrophins (NTs), proteins that modulate the functioning and development of the central nervous system, such as brain-derived neurotrophic factor (BDNF), have been associated with OSA, primarily due to their probable involvement in offsetting the decline in cognitive functions which accompanies OSA. However, NTs influence multiple aspects of biological functioning, such as immunity. Thus, extensive evaluation of their role in OSA might enlighten the mechanism behind some of its elusive features, such as the increased risk of developing an immune-mediated disease or the association of OSA with cardiovascular diseases. In this review, we examine the interactions between NTs and OSA and discuss their contribution to OSA pathophysiology, complications, as well as comorbidities

Adolescent Congenital Central Hypoventilation Syndrome: An Easily Overlooked Diagnosis

Congenital central hypoventilation syndrome (CCHS), also known as Ondine’s curse, is a rare, potentially fatal genetic disease, manifesting as a lack of respiratory drive. Most diagnoses are made in pediatric patients, however late-onset cases have been rarely reported. Due to the milder symptoms at presentation that might easily go overlooked, these late-onset cases can result in serious health consequences later in life. Here, we present a case report of late-onset CCHS in an adolescent female patient. In this review we summarize the current knowledge about symptoms, as well as clinical management of CCHS, and describe in detail the molecular mechanism responsible for this disorder

Disruption of Circadian Rhythm Genes in Obstructive Sleep Apnea Patients—Possible Mechanisms Involved and Clinical Implication

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

BDNF and proBDNF Serum Protein Levels in Obstructive Sleep Apnea Patients and Their Involvement in Insomnia and Depression Symptoms

Introduction: Obstructive sleep apnea (OSA) is a disorder that, apart from somatic sequelae, increases the risk of developing psychiatric conditions. Brain-derived neurotrophic factor (BDNF) signaling pathway is involved in the pathophysiology of depression and insomnia. Therefore, the study aimed to investigate differences in concentrations of BDNF and proBDNF in patients with OSA and healthy individuals, to evaluate diurnal changes of these proteins, and to assess the correlations with psychiatric symptoms. Methods: Sixty individuals following polysomnography (PSG) were divided into two groups based on the apnea-hypopnea index (AHI): OSA patients (AHI ≥ 30; n = 30) and control group (AHI n = 30). Participants filled out questionnaires: Beck Depression Inventory (BDI), Athens Insomnia Scale (AIS), and Pittsburgh Sleep Quality Index (PSQI). Peripheral blood was collected before and after PSG. Protein concentrations were measured using ELISA. OSA group was divided into subgroups: AIS (−)/AIS (+) (AIS > 5), PSQI (−)/PSQI (+) (PSQI > 5), and BDI (−)/BDI (+) (BDI > 19). Results: No differences in BDNF and proBDNF protein levels were observed between OSA and the control groups. However, BDNF and proBDNF evening protein concentrations were higher in the AIS (+) and PSQI (+) groups (p p = 0.047 and p = 0.003, respectively). Conclusions: BDNF signaling pathway might be involved in the pathophysiology of depression and insomnia in patients with OSA. BDNF and proBDNF protein levels might be useful in defining OSA phenotypes

Table_1_Evaluation of daytime sleepiness and insomnia symptoms in OSA patients with a characterization of symptom-defined phenotypes and their involvement in depression comorbidity—a cross-sectional clinical study.docx

IntroductionRecent research highlights the significance of insomnia and sleepiness, shifting from obstructive sleep apnea (OSA) severity and sleep structure, in defining OSA phenotypes.ObjectivesThis study aimed to characterize insomnia and sleepiness associated with OSA phenotypes and assess their involvement in depression symptoms (DS) in OSA.Materials and methodsThis cross-sectional, clinical study included 181 participants who underwent polysomnography (PSG) and filled out questionnaires, including the Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), and Beck Depression Index (BDI). They were categorized into phenotypes: insomnia–sleepiness (I + S; ESS ≥ 11; ISI ≥ 15; n = 20), sleepiness (S; ESS ≥ 11; ISI ResultsA linear regression model for the BDI score (R2 = 0.357, p ConclusionUsing clinical features for OSA phenotyping holds promise for finding OSA individuals with increased risk for DS occurrence.</p

Table_2_Evaluation of daytime sleepiness and insomnia symptoms in OSA patients with a characterization of symptom-defined phenotypes and their involvement in depression comorbidity—a cross-sectional clinical study.docx

IntroductionRecent research highlights the significance of insomnia and sleepiness, shifting from obstructive sleep apnea (OSA) severity and sleep structure, in defining OSA phenotypes.ObjectivesThis study aimed to characterize insomnia and sleepiness associated with OSA phenotypes and assess their involvement in depression symptoms (DS) in OSA.Materials and methodsThis cross-sectional, clinical study included 181 participants who underwent polysomnography (PSG) and filled out questionnaires, including the Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), and Beck Depression Index (BDI). They were categorized into phenotypes: insomnia–sleepiness (I + S; ESS ≥ 11; ISI ≥ 15; n = 20), sleepiness (S; ESS ≥ 11; ISI ResultsA linear regression model for the BDI score (R2 = 0.357, p ConclusionUsing clinical features for OSA phenotyping holds promise for finding OSA individuals with increased risk for DS occurrence.</p

Table_3_Evaluation of daytime sleepiness and insomnia symptoms in OSA patients with a characterization of symptom-defined phenotypes and their involvement in depression comorbidity—a cross-sectional clinical study.docx

IntroductionRecent research highlights the significance of insomnia and sleepiness, shifting from obstructive sleep apnea (OSA) severity and sleep structure, in defining OSA phenotypes.ObjectivesThis study aimed to characterize insomnia and sleepiness associated with OSA phenotypes and assess their involvement in depression symptoms (DS) in OSA.Materials and methodsThis cross-sectional, clinical study included 181 participants who underwent polysomnography (PSG) and filled out questionnaires, including the Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), and Beck Depression Index (BDI). They were categorized into phenotypes: insomnia–sleepiness (I + S; ESS ≥ 11; ISI ≥ 15; n = 20), sleepiness (S; ESS ≥ 11; ISI ResultsA linear regression model for the BDI score (R2 = 0.357, p ConclusionUsing clinical features for OSA phenotyping holds promise for finding OSA individuals with increased risk for DS occurrence.</p