Cortical activation during the verbal fluency task for obstructive sleep apnea patients with depressive symptoms: A multi-channel fNIRS study.

Update on Obstructive Sleep Apnea: Implications for Neuropsychiatry.

Obstructive sleep apnoea (OSA) is associated with airways inflammation; a key role in this regard seems to be played by nitric oxide (NO). The aim of this study was to measure exhaled NO and expression of its enzyme, the inducible nitric oxide synthase (iNOS) in cells of induced sputum in OSA patients and in obese subjects without sleep apnoea and to correlate these inflammatory markers with severity of OSA. We enrolled 18 obese patients with OSA (10 men, age 48.2 +/- 8.4 years), 15 obese patients without OSA (eight men, age 52.8 +/- 11 years) and 10 healthy subjects (five men, age 42 +/- 4 years). Exhaled NO was measured using a chemiluminescence analyser; iNOS expression was measured in the sputum cells by immunocytochemistry. Exhaled NO resulted significantly increased in OSA and in obese patients (23.1 +/- 2.1 and 17.9 +/- 2.1 p.p.b.) than in healthy subjects (7.2 +/- 0.6 p.p.b.; P < 0.001). OSA and obese patients showed a higher percentage of neutrophils and a lower percentage of macrophages in the induced sputum compared to healthy subjects. In addition, OSA and obese patients showed higher iNOS expression in neutrophils and in macrophages with respect to healthy subjects. A positive correlation between exhaled NO, iNOS expression and AHI was observed. These data confirm the presence of airway inflammation in OSA and in obese patients, and suggest the possible role for NO and iNOS expression in neutrophils of the induced sputum as noninvasive markers to identify and monitor the airway inflammation in these subjects.

Background: Insulin resistance (IR) is a characteristic feature in patients who are developing Type 2 diabetes in the prediabetic stage. Obstructive sleep apnea (OSA) is a breathing disorder characterized by frequent episodes of reduced airflow due to obstruction in the upper airway while sleeping. OSA is associated with intermittent hypoxia and predisposition to increased IR. Aims and Objectives: This study investigates the extent of IR in prediabetics and OSA patients and also compares serum nitric oxide (NO) levels in the three study groups. Materials and Methods: Three groups each comprising of 50 people were selected: Group I - control group; Group II - prediabetic patients; and Group III - OSA patients. Fasting blood glucose, insulin, and NO levels were measured in these subjects and IR calculated. Results: Insulin levels and IR were significantly higher in OSA and prediabetic patients when compared to control subjects. There was no significant difference in insulin levels (P > 0.05) between OSA and prediabetic groups. OSA group had significantly lower level of NO compared to both control and prediabetic groups. Conclusion: High insulin levels and IR in prediabetics indicate that they are prone to develop Type 2 diabetes. The same findings in OSA patients could mean that they are also prone to develop Type 2 diabetes. NO levels are significantly low in OSA patients. Low NO level has been associated with hypoxia; this molecule with its wide array of actions may be involved in glucose homeostasis.

Simple SummaryObstructive sleep apnea (OSA) increases the risk of numerous cancers. Nevertheless, testicular cancer prevalence in OSA patients has not been documented. Based on KNHIS data, this study examines OSA’s effect on testicular cancer incidence. A total of 152,801 newly diagnosed male adult OSA patients and 764,005 controls were studied. Even after confounding correction, OSA’s HR for testicular cancer was 1.58 (95% CI: 0.92–2.60). The subgroup analysis showed a 3.39 (95% CI: 1.08–10.06) HR for testicular cancer in those over 65. The 20–40 and 40–65 age groups had no significant HR. OSA may not affect testicular cancer in adults in general. However, those over 65 may be more susceptible to OSA-related testicular cancer than younger individuals.Obstructive sleep apnea (OSA) has been linked to an increased risk of acquiring many types of cancer. No data on the prevalence of testicular cancer in OSA patients have been reported in the literature. The goal of the present investigation is to find out the impact of OSA on the incidence of testicular cancer based on the Korea National Health Insurance Service (KNHIS) dataset. A cohort of adult male patients newly registered with OSA in the KNHIS data from 2007 to 2014 who had no history of any previous cancer diagnosis was included. The main outcome measure was newly diagnosed testicular cancer in the National Medical Expenses Support Program. The control group was set at five times larger than the OSA group, and it was matched with age and sex. The cumulative incidence and hazard ratio (HR) for the development of testicular cancer were compared between the OSA and control groups. Further subgroup analysis was conducted in the three different age groups. In the study period, a total of 152,801 male adult patients newly diagnosed with OSA were included, whereas 764,005 individuals were recruited as the control group. The HR of OSA for developing testicular cancer was 1.58 (95% confidence interval [CI]: 0.92–2.60), showing no significant HR regardless of confounding adjustment. However, the subgroup analysis revealed a significantly increased HR to develop testicular cancer of 3.39 (95% CI: 1.08–10.06) in groups aged more than 65, whereas the age ranges of 20–40 and 40–64 showed no significance (1.19 (0.44–2.75) and 1.27 (0.50–2.80), respectively). OSA may not influence the incidence of testicular cancer in the general adult population. However, compared to younger males, males over 65 may be more susceptible to OSA when it comes to developing testicular cancer.

Introduction: The search of biochemical markers of endothelial dysfunction: lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1)—involved in atherosclerotic plaques formation—and endothelin-1 (ET-1)—potent vasoconstrictor-might help in detecting obstructive sleep apnea (OSA) patients at high risk of cardiovascular diseases. Material and Methods: In 71 OSA patients (apnoea/hypopnoea index, AHI 28.2 ± 17.9/hour) and in 21 healthy controls the serum levels of LOX-1 and ET-1 were measured. Results: There were increased levels of ET-1 (1.58 ± 0.65 vs. 1.09 ± 0.38 pg/mL; p < 0.001) but not of LOX-1 in OSA patients as compared with healthy controls. In the patients’ group ET-1 levels negatively correlated with serum LDL levels. LOX-1 levels positively correlated with fasting glucose levels and were higher in the patients with than without diabetes. Neither ET-1 nor LOX-1 correlated with OSA severity. In mild OSA patients, there was a negative correlation between LOX-1 and mean arterial oxygen saturation during sleep. In severe OSA patients, there was a positive correlation between LOX-1 levels and uric acid. Conclusion: There is endothelial dysfunction in OSA patients as indicated by increased serum levels of ET-1 and possibly endothelial dysfunction in diabetic OSA patients as indicated by increased serum levels of LOX-1 and its correlation with fasting glucose levels.

Systemic and airway inflammation in sleep apnea and obesity: the role of ICAM-1 and IL-8

Endogenous carbon monoxide (CO) levels are recognized to be a surrogate marker of oxidative stress. No study has evaluated both exhaled and blood CO at the same time in obstructive sleep apnea (OSA) patients. Here we provide evidence that exhaled CO levels positively correlated with hypoxia during sleep in OSA patients, but blood CO levels did not, and that continuous positive airway pressure therapy significantly decreased exhaled CO levels in the OSA group, but did not significantly affect blood CO.

The aim of this research was to test the hypothesis that changes in the intestinal microbiota lead to the alternation of histidine metabolism and Th17/Treg cell imbalance in obstructive sleep apnea (OSA) patients. In total, 46 subjects were enrolled in the study, with 32 subjects in the OSA group and 14 in the healthy group, according to polysomnography examinations. Basic clinical characteristics were collected for this analysis. Feces were collected from OSA patients to detect the gut microbiota using 16S rRNA sequencing. Peripheral blood was obtained to detect the Th17/Treg cell ratio by flow cytometry. The present research demonstrated that at the phylum level, OSA patients have a disproportionate Firmicutes/Bacteroidetes ratio with increased Firmicutes and decreased Bacteroidetes in the gut microbiota compared to the healthy population. A Metastats analysis also indicated that the family Rikenellaceae was prevalent in the control group but not the OSA group. In addition, the abundance of Clostridium_XlVa was reduced and the abundance of Alistipes was elevated in healthy subjects at the genus level. Furthermore, a Phylogenetic Investigation of Communities by Reconstruction of Unobserved States analysis identified the alternation of metabolic pathways in OSA patients. The current study also identified an imbalance of Th17/Treg cells in OSA patients, with OSA patients having an elevated number of Treg cells compared to the control group. We determined that the abundance of Rikenellaceae and Alistipes increased and Clostridium_XlVa decreased in patients with OSA, which may have caused an imbalance in the proportion of Th17/Treg cells.

Background and Objective The precise pathophysiology of cognitive impedance and mental illness in obstructive sleep apnea (OSA) patients remains elusive. Therefore, there is a need for studies on novel diagnoses and therapeutic strategies for cognitive impairment in OSA patients. This work aimed to evaluate cerebral hypoxemia, its consequences on brain metabolism, and local and systemic inflammation, and their subsequent impact on cognitive and psychological functioning.Methods This cross-sectional case-control study was conducted on 30 eligible OSA patients and 20 age/sex-matched healthy controls. All the participants underwent one-night polysomnography, and cognitive evaluation was done using the Mini-Mental State Examination, Montreal Cognitive Assessment, Brief Kingston Standardized Cognitive Assessment, D2 Test of Consideration (to evaluate attention problems), and Wisconsin card sorting test. The psychiatric assessment included the Arabic form of the Hamilton Depression Rating Scale and Beck Depression Inventory-II. A radiology assessment was done using proton magnetic resonance spectroscopy. Neurophysiological assessment was done using the potential cortical (N20) latency and amplitude of somatosensory evoked potential. Laboratory examinations included serum levels of NF-κB, HMGB1, and HIF-1α.Results Polysomnography demonstrated noteworthy increase in the apnea-hypopnea index, respiratory disturbance index, arousal index, snoring index, and wake after sleep onset. It also showed diminished sleep efficiency, total sleep time, and SaO2 nadir in the OSA group. Neuropsychological scales demonstrated poor performance in global cognitive tests, particular cognitive domains impedance, and depression in the OSA group, with noteworthy differences within the group. Magnetic resonance spectroscopy highlighted that OSA patients had a noteworthy bilateral decrement in N-acetylaspartate (NAA) peak, creatine peak, and NAA/choline proportion and an increment in choline peak, lipid peak, lactate peak, choline/creatine proportion, and NAA/creatine proportion in the frontal white matter, hippocampus, and parieto-occipital cortex. Moreover. OSA patients had either missing or decreased amplitude and delayed latency of N20. There was a noteworthy rise of serum inflammatory marker NF-κB, HMGB1, and oxidative stress marker HIF-1α in OSA patients.Conclusions Chronic intermittent hypoxia with resulting amplified inflammatory and oxidative stress in OSA patients may affect brain metabolism; consequently, leading to cognitive and psychological dysfunctions.

Some, but not all, researchers report that obstructive sleep apnea (OSA) patients experience increased depressive symptoms. Many psychological symptoms of OSA are explained in part by other OSA comorbidities (age, hypertension, body mass). People who use more passive and less active coping report more depressive symptoms. We examined relationships between coping and depressive symptoms in OSA. N/A. 64 OSA (respiratory disturbance index (RDI) > or = 15) patients were studied with polysomnography and completed Ways of Coping (WC), Profile of Mood States (POMS), Center for Epidemiological Studies-Depression (CESD) scales. WC was consolidated into Approach (active) and Avoidance (passive) factors. Data were analyzed using SPSS 9.0 regression with CESD as the dependent variable and WC Approach and Avoidance as the independent variables. N/A. WC Approach factor (B=-1.105, beta=-.317, p=.009) was negatively correlated and WC Avoidance factor (B=1.353, beta=.376, p=.007) was positively correlated with CESD scores. These factors explained an additional 8% of CESD variance (p<.001) beyond that explained by the covariates: demographic variables, RDI, and fatigue (as measured by the POMS). More passive and less active coping was associated with more depressive symptoms in OSA patients. The extent of depression experienced by OSA patients may not be due solely to effects of OSA itself. Choice of coping strategies may help determine who will experience more depressive symptoms.

To analyze differences in mandibular cortical width (MCW) among children diagnosed with obstructive sleep apnea (OSA) or at high- or low-risk for OSA. A total of 161 children were assessed: 60 children with polysomnographically diagnosed OSA, 56 children presenting symptoms suggestive of high-risk for OSA, and 45 children at low risk for OSA. Children at high- and low-risk for OSA were evaluated through the Pediatric Sleep Questionnaire. MCW was calculated using ImageJ software from panoramic radiograph images available from all participants. Differences between MCW measurements in the 3 groups were evaluated using analysis of covariance and Bonferroni post-hoc tests, with age as a covariate. The association between MCW and specific cephalometric variables was assessed through regression analysis. The participants' mean age was 9.6 ± 3.1 years (59% male and 41% female). The mean body mass index z-score was 0.62 ± 1.3. The polysomnographically diagnosed OSA group presented smaller MCW than the group at low-risk for OSA (mean difference = -0.385 mm, P = .001), but no difference with the group at high-risk for OSA (polysomnographically diagnosed OSA vs high-risk OSA: P = .085). In addition, the MCW in the group at high-risk for the OSA was significantly smaller than the group at low-risk for the OSA (mean difference = -0.301 mm, P = .014). The cephalometric variables (Sella-Nasion-A point angle (SNA) and Frankfort - Mandibular Plane angle (FMA)) explained only 8% of the variance in MCW. Reductions in MCW appear to be present among children with OSA or those at high-risk for OSA, suggesting potential interactions between mandibular bone development and/or homeostasis and pediatric OSA. Fernandes Fagundes NC, d'Apuzzo F, Perillo L, et al. Potential impact of pediatric obstructive sleep apnea on mandibular cortical width dimensions. J Clin Sleep Med. 2021;17(8):1627-1634.

Background – Obstructive Sleep Apnea (OSA) is linked with endothelial dysfunction, posing a significant risk for cardiovascular diseases. The non-invasive assessment of endothelial function through passive leg movement (PLM) offers a novel diagnostic avenue. This study explores PLM's efficacy in differentiating between healthy individuals and those with OSA, alongside evaluating the impact of oral vitamin C on endothelial function within these groups. Materials and Methods: The study enrolled 26 male subjects, divided equally into healthy and OSA groups. PLM was performed using an isokinetic machine to assess femoral artery blood flow (FBF) and blood velocities (FBVs) via Doppler ultrasound. Subjects consumed 1000mg of oral vitamin C, with measurements repeated post-consumption. Data analysis involved repeated measures ANOVA to evaluate the diagnostic capability of PLM and the effect of vitamin C on FBF responses. Results: A significant difference in FBF was observed between OSA and healthy groups (healthy: 162.1 ml/min, OSA: 76.6 ml/min; p &lt; 0.05), confirming PLM's diagnostic potential. However, vitamin C administration did not significantly alter FBF responses in OSA patients (pre-vitamin C: 76.6 ml/min, post-vitamin C: 79.9 ml/min; p &gt; 0.05), challenging the anticipated benefits of oral vitamin C on endothelial function. Conclusion: PLM effectively distinguishes between healthy individuals and those with OSA, highlighting its diagnostic utility. Nonetheless, oral vitamin C did not improve endothelial dysfunction in OSA patients, suggesting the need for further research on alternative administration methods or dosages.

There is a high rate of obstructive sleep apnea (OSA) in patients with syndromic craniosynostosis (SCS). Little is known about the airway anatomy in this population. The purpose of this study is to characterize the 3 dimensional (3D) upper airway in patients with SCS with and without OSA. This is a retrospective study of patients with SCS treated at Boston Children's Hospital from 2000 to 2015. Patients were divided into OSA and no-OSA groups based on polysomnography. Predictor variables included age, sex, body mass index (BMI), and 3D upper airway measurements. The primary outcome variable was the presence or absence of OSA. Secondary outcome variables were apnea-hypopnea index and oxygen saturation nadir. Descriptive and bivariate statistics were computed, and significance was set as P < .05. There were 24 patients: 16 in the OSA group and 8 in the no-OSA group. The 2 groups did not differ significantly by age, BMI, or syndromic diagnosis. The presence of OSA was associated with a smaller minimum retropalatal cross-sectional area (minRPCSA; P < .001). In a logistic regression model controlling for age, sex, and upper airway length, minRPCSA was the primary predictor of OSA (P ≤ .002). Receiver operating characteristic analysis determined minRPCSA = 55.3 mm2 to be the optimal diagnostic threshold for OSA, with sensitivity = 100% and specificity = 87.5% (P < .001). A minRPCSA ≤55.3 mm2 is predictive of the presence of OSA in patients with SCS.

Objective:This study aimed to compare the cephalometric characteristics of obstructive sleep apnea (OSA) patients with those of healthy subjects and to determine possible relationships between cephalometric measurements of OSA patients and control subjects.Methods:Standardized lateral cephalograms of 16 OSA patients and 16 healthy controls were obtained. Airway dimensions and dentofacial parameters were measured using a cephalometric analysis program (Dolphin Imaging Cephalometric and Tracing Software, Chatsworth, CA, USA). All statistical analyses were conducted using SPSS version 17.0.0 (SPSS Inc., Chicago, IL, USA). Descriptive statistics were calculated for all measurements, and the Mann–Whitney U test was used to evaluate intergroup differences.Results:Midface length was significantly shorter and upper lip E-plane length was significantly longer in the OSA group than in the controls (P<.05). SNA, SNB, and mandibular plane angles (GoGn-SN), anterior and posterior facial heights, and posteroanterior face height ratio were similar in both groups. Maxillary length was slightly longer in the OSA group, whereas the mandibular length showed a slight increase in the control group (P<.05). The axial inclination of the lower incisor to its respective plane was normal, whereas the upper incisor was significantly protrusive (P<.05) in the OSA group. Distance between the hyoid and mandible was significantly greater in the OSA group than in the controls, indicating that the hyoid bone was positioned more downward in the OSA group (P<.05).Conclusions:In this study, the patients with OSA demonstrated significant differences in several craniofacial measurements. OSA patients showed reduced midface length and inferiorly placed hyoid bone and tended to have smaller airway dimensions.

Depressive symptoms are common in obstructive sleep apnea (OSA) patients, and brain injury occurs with both OSA and depression independently. The objective was to determine whether brain alterations in OSA bear relationships to depressive symptoms. Cross-sectional study. University-based medical center. 40 treatment-naive OSA subjects and 61 control subjects without diagnosed psychopathology. None. Whole-brain maps of T2 relaxation time, a measure sensitive to injury, were calculated from magnetic resonance images, transformed to common space, and smoothed. Control and OSA groups were classified by Beck Depression Inventory (BDI)-II scores (> or =12 symptomatic, <10 asymptomatic for depressive symptoms). The OSA group separated into 13 symptomatic (mean +/- SD: BDI-II 21 +/- 8; age 47.6 +/- 11; apnea hypopnea index [AHI] 28.3 +/- 17), and 27 asymptomatic (4 +/- 3; 47.5 +/- 8; 31.5 +/- 16) subjects. The control group included 56 asymptomatic (BDI-II 2.5 +/- 2.6; age 47.3 +/- 9) subjects. Asymptomatic OSA subjects exhibited higher AHI. T2 maps were compared between groups (ANCOVA), with age and gender as covariates. Injury appeared in symptomatic vs asymptomatic OSA subjects in the mid- and anterior cingulate, anterior insular, medial pre-frontal, parietal, and left ventrolateral temporal cortices, left caudate nucleus, and internal capsule. Relative to asymptomatic controls, symptomatic OSA patients showed damage in the bilateral hippocampus and caudate nuclei, anterior corpus callosum, right anterior thalamus, and medial pons. Neural injury differed between OSA patients with and without depressive symptoms. Depressive symptoms may exacerbate injury accompanying OSA, or introduce additional damage in affective, cognitive, respiratory, and autonomic control regions.