Lack of structural brain alterations associated with insomnia: findings from the ENIGMA-Sleep Working Group.

Existing neuroimaging studies have reported divergent structural alterations in insomnia disorder (ID). In the present study, we performed a large-scale coordinated meta-analysis by pooling structural brain measures from 1085 subjects (mean [SD] age 50.5 [13.9] years, 50.2% female, 17.4% with insomnia) across three international Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA)-Sleep cohorts. Two sites recruited patients with ID/controls: Freiburg (University of Freiburg Medical Center, Freiburg, Germany) 42/43 and KUMS (Kermanshah University of Medical Sciences, Kermanshah, Iran) 42/49, while the Study of Health in Pomerania (SHIP-Trend, University Medicine Greifswald, Greifswald, Germany) recruited population-based individuals with/without insomnia symptoms 75/662. The influence of insomnia on magnetic resonance imaging-based brain morphometry using an insomnia brain score was then assessed. Within each cohort, we used an ordinary least-squares linear regression to investigate the link between the individual regional cortical and subcortical volumes and the presence of insomnia symptoms. Then, we performed a fixed-effects meta-analysis across cohorts based on the first-level results. For the insomnia brain score, weighted logistic ridge regression was performed on one sample (Freiburg), which separated patients with ID from controls to train a model based on the segmentation measurements. Afterward, the insomnia brain scores were validated using the other two samples. The model was used to predict the log-odds of the subjects with insomnia given individual insomnia-related brain atrophy. After adjusting for multiple comparisons, we did not detect any significant associations between insomnia symptoms and cortical or subcortical volumes, nor could we identify a global insomnia-related brain atrophy pattern. Thus, we observed inconsistent brain morphology differences between individuals with and without insomnia across three independent cohorts. Further large-scale cross-sectional/longitudinal studies using both structural and functional neuroimaging are warranted to decipher the neurobiology of insomnia.

Interleukin-1α and tumor necrosis factor α as an inducer for reactive-oxygen-species-mediated NOD-like receptor protein 1/NOD-like receptor protein 3 inflammasome activation in mononuclear blood cells from individuals with chronic insomnia disorder.

BACKGROUND AND PURPOSE: There is some evidence that cytokines may play an important role in sleep deprivation; however, the underlying mechanisms are still unknown. So, the present study aimed to evaluate the relationship between NOD-like receptor protein 1 (NLRP1) and NOD-like receptor protein 3 (NLRP3) inflammasome activation of blood cells and serum levels of cytokines in individuals with chronic insomnia disorder (CID). METHODS: Blood samples were collected from 24 individuals with CID and 24 healthy volunteers. The inflammasome activation was evaluated using real-time polymerase chain reaction of NLRP1, NLRP3, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and caspase-1; western blot of NLRP1 and NLRP3; caspase-1 activity assay; and serum levels of interleukin-1ß (IL-1ß), IL-18 and other cytokines using enzyme-linked immunosorbent assay. Reactive oxygen species generation in blood cells were detected by flow cytometry assay. Also, magnetic resonance imaging scans were obtained on a Siemens Magnetom Avanto 1.5 T MRI whole-body scanner using an eight-channel head coil. RESULTS: Increased activity of NLRP1 and NLRP3 inflammasomes in blood cells, increased serum levels of pro-inflammatory cytokines and decreased serum levels of IL-10 and transforming growth factor ß in individuals with CID were found. Significant correlation was observed between increased serum concentration of IL-1ß and the severity of insomnia in individuals with CID. The levels of reactive oxygen species in blood cells were found to be correlated with IL-1α and tumor necrosis factor α concentrations in sera from individuals with CID. Moreover, the individuals with CID demonstrated increased right cerebellum cortex and lateral ventricle mean diffusivity bilaterally compared to controls. CONCLUSIONS: This study provided new insights on the pathogenesis of CID and the effects of cytokines on inflammasome activation.

ENIGMA-Sleep: Challenges, opportunities, and the road map.

Neuroimaging and genetics studies have advanced our understanding of the neurobiology of sleep and its disorders. However, individual studies usually have limitations to identifying consistent and reproducible effects, including modest sample sizes, heterogeneous clinical characteristics and varied methodologies. These issues call for a large-scale multi-centre effort in sleep research, in order to increase the number of samples, and harmonize the methods of data collection, preprocessing and analysis using pre-registered well-established protocols. The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium provides a powerful collaborative framework for combining datasets across individual sites. Recently, we have launched the ENIGMA-Sleep working group with the collaboration of several institutes from 15 countries to perform large-scale worldwide neuroimaging and genetics studies for better understanding the neurobiology of impaired sleep quality in population-based healthy individuals, the neural consequences of sleep deprivation, pathophysiology of sleep disorders, as well as neural correlates of sleep disturbances across various neuropsychiatric disorders. In this introductory review, we describe the details of our currently available datasets and our ongoing projects in the ENIGMA-Sleep group, and discuss both the potential challenges and opportunities of a collaborative initiative in sleep medicine.

Increased the circulating levels of malondialdehyde in patients with obstructive sleep apnea: a systematic review and meta-analysis.

PURPOSE: Obstructive sleep apnea (OSA) is a prevalent sleep disorder associated with increased risk of cardiovascular disease. Several studies have demonstrated elevated oxidative stress in patients with OSA. This oxidative stress is a direct inducer of lipid peroxidation. Malondialdehyde (MDA), a robust marker of lipid peroxidation, has been evaluated in patients with OSA but results have been inconsistent. The present systematic review and meta-analysis was performed to quantify the circulating levels of MDA in patients with OSA compared to controls. METHODS: Search was performed in data bases of PubMed, Scopus, EMBASE, Web of Science, and Cochrane library, to find out those studies that measured MDA in patients with OSA compared to controls. RESULTS: The search produced 563 records and after removing duplicates, 383 records remained. Screening by title and abstract and the evaluation of the full text resulted in the selection of 14 articles, which were included in the meta-analysis. Pooled analysis demonstrated higher levels of MDA in the patients compared to the controls (SMD (95% CI): 1.18 (0.68, 1.68), p < 0.0001). CONCLUSION: The results of this meta-analysis demonstrated considerable elevation of MDA in patients with OSA compared to controls. The meta-analysis also indicated a positive association of MDA levels with the degree of severity of OSA. These results suggest a state of increased lipid peroxidation in patients with OSA.

Relationship between Sleep Problems and Self-Injury: A Systematic Review.

Objective/Background: Previous studies suggested that sleep problems were related to non-suicidal self-injury. The current systematic review investigated more thoroughly this relationship.Methods: PubMED and Embase databases were searched. The keywords were "self-injury" OR "self-harm" OR "non-suicidal self-injury" OR "self-injurious behavior" OR "self-destructive behavior" OR "self-mutilation" AND "sleep problem" OR "sleep disturbance" OR insomnia OR nightmare OR "poor sleep quality" or "sleep disorders." A total of 16 studies were included in the present review.Results: The pattern of results indicated that sleep problems such as short sleep duration, sleep disturbances, and poor sleep quality were associated with non-suicidal self-injury. Additionally, emotional dysregulation, depression, and post-traumatic stress disorder appeared to mediate this relationship. Above all adolescents and young adults with sleep disruptions were at higher risk of non-suicidal self-injury.Conclusions:g Interventions to improve sleep quality and sleep duration might concomitantly decrease the risk of non-suicidal self-injury.

Circulating levels of oxidized low-density lipoprotein in patients with obstructive sleep apnea: a systematic review and meta-analysis.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with an increased risk of developing atherosclerotic cardiovascular disease (ASCVD). Patients with OSA have increased levels of oxidative stress and several studies have shown higher levels of oxidative stress markers. Oxidized-LDL (Ox-LDL) is an important risk factor for ASCVD and a number of studies have measured its levels in patients with OSA, though results from these studies are conflicting. This meta-analysis aimed to reassess circulating levels of Ox-LDL in patients with OSA in comparison with controls. METHODS: Studies evaluating Ox-LDL levels in patients with OSA and controls were explored in databases of PubMed, EMBASE, Scopus, and Web of Science. Two authors independently performed the search from January 1990 to February 2019. Two authors independently screened the studies according to title, abstract, and full text. In addition, the Newcastle-Ottawa Quality Assessment Scale was utilized to evaluate the quality of the studies. The impact of OSA on Ox-LDL levels was determined using the random effects model. RESULTS: Of 195 articles retrieved, 98 were duplicates, 49 were excluded by title, 20 excluded by abstract, and 22 by full texts. Six eligible studies were included in the meta-analysis. Pooled analysis demonstrated that Ox-LDL increased in patients with OSA compared with controls. In addition, subgroup analysis revealed that studies matching age or BMI between OSA patients and controls showed no significant difference between patients with OSA and healthy controls, while unmatched studies had higher levels of Ox-LDL in patients with OSA in comparison with controls. CONCLUSION: This study demonstrated higher circulating concentrations of Ox-LDL in patients with OSA. However, no significant difference was found in studies in which patients and controls were matched for age and BMI, suggesting the involvement of these two confounding factors as a cause for elevated concentrations of circulating Ox-LDL in patients with OSA.

Impact of low level radiation on concentrations of some trace elements in radiation workers.

INTRODUCTION: Small variations in trace element levels may cause important physiological changes in the human body. This study aims to evaluate five important trace elements in radiation workers. METHOD: In this study, 44 radiation workers and an equal number of non-radiation workers were selected as the case and control group, respectively. The concentrations of iron, magnesium, zinc, copper, and selenium in the serum of the participants were measured using an Atomic Absorption Spectrometry (AAS). RESULTS: The mean concentrations of iron, magnesium, zinc, copper, and selenium for the case group were 107.3 µg/dl, 2.3 mg/dl, 80.9 µg/dl, 112.6 µg/dl and 216.7 ng/ml, respectively. The results for the control group were 121.9 µg/dl, 2.3 mg/dl, 82.3 µg/dl, 112.8 µg/dl and 225.2 ng/ml, respectively. CONCLUSIONS: The mean concentration of iron in the case group was significantly lower than the control group (p-value = 0.012), while the concentrations of other elements in both of the groups were not significantly different. In the case group, except magnesium (p-value = 0.021), no significant relationship was found between age and the elemental concentrations. According to Spearman's test, there was a meaningful statistical correlation between the sex and concentration of iron, Mg, Zn, and Se. Also, the correlation between the concentration of magnesium and the weights of radiation workers was significant (p-value =0.044).

Monte Carlo simulation and film dosimetry for electron therapy in vicinity of a titanium mesh.

Titanium (Ti) mesh plates are used as a bone replacement in brain tumor surgeries. In the case of radiotherapy, these plates might interfere with the beam path. The purpose of this study is to evaluate the effect of titanium mesh on the dose distribution of electron fields. Simulations were performed using Monte Carlo BEAMnrc and DOSXYZnrc codes for 6 and 10 MeV electron beams. In Monte Carlo simulation, the shape of the titanium mesh was simulated. The simulated titanium mesh was considered as the one which is used in head and neck surgery with a thickness of 0.055 cm. First, by simulation, the percentage depth dose was obtained while the titanium mesh was present, and these values were then compared with the depth dose of homogeneous phantom with no titanium mesh. In the experimental measurements, the values of depth dose with titanium mesh and without titanium mesh in various depths were measured. The experiments were performed using a RW3 phantom with GAFCHROMIC EBT2 film. The results of experimental measurements were compared with values of depth dose obtained by simulation. In Monte Carlo simulation, as well as experimental measurements, for the voxels immediately beyond the titanium mesh, the change of the dose were evaluated. For this purpose the ratio of the dose for the case with titanium to the case without titanium was calculated as a function of titanium depth. For the voxels before the titanium mesh there was always an increase of the dose up to 13% with respect to the same voxel with no titanium mesh. This is because of the increased back scattering effect of the titanium mesh. The results also showed that for the voxel right beyond the titanium mesh, there is an increased or decreased dose to soft tissues, depending on the depth of the titanium mesh. For the regions before the depth of maximum dose, there is an increase of the dose up to 10% compared to the dose of the same depth in homogeneous phantom. Beyond the depth of maximum dose, there was a 16% decrease in dose. For both 6 and 10 MeV, before the titanium mesh, there was always an increase in dose. If titanium mesh is placed in buildup region, it causes an increase of the dose and could lead to overdose of the adjacent tissue, whereas if titanium mesh is placed beyond the buildup region, it would lead to a decrease in dose compared to the homogenous tissue.

Reduced White Matter Fiber Density in Patients with Multiple Sclerosis.

Introduction: Improved understanding of multiple sclerosis (MS) symptomatology, disease mechanisms, and clinical effectiveness can be achieved by investigating microstructural damage. The aim was to gain deeper insights into changes in white matter (WM) tracts in MS patients. Methods: Diffusion magnetic resonance imaging-based tractography was utilized to segment WM tracts into regions of interest for further quantitative analysis. However, tractography is susceptible to false-positive findings, reducing its specificity and clinical feasibility. To address these limitations, the Convex Optimization Modeling for Microstructure Informed Tractography (COMMIT) technique was used. COMMIT was used to derive measures of intracellular compartment (IC) and isotropic compartments from multishell diffusion data of 40 healthy controls (HCs) and 40 MS patients. Results: The analysis revealed a widespread pattern of significantly decreased IC values in MS patients compared with HCs across 61,581 voxels (pFWE < 0.05, threshold-free cluster enhancement [TFCE] corrected). Similar WM structures studied using the fractional anisotropy (FA) value also showed a reduction in FA among MS patients compared with HCs across 57,304 voxels (pFWE < 0.05, TFCE corrected). Out of the 61,581 voxels exhibiting lower IC, a substantial overlap of 47,251 voxels (76.72%) also demonstrated lower FA in MS patients compared with HCs. Discussion: The data suggested that lower IC values contributed to the explanation of FA reductions. In addition, IC showed promising potential for evaluating microstructural abnormalities in WM in MS, potentially being more sensitive than the frequently used FA value.

Circulating levels of miR125a, miR126, and miR146a-5p in patients with obstructive sleep apnea and their relation with markers of endothelial dysfunction.

BACKGROUND: obstructive sleep apnea (OSA) is a prevalent sleep disorder that is associated with increased risk factors for cardiovascular diseases (CVDs). Oxidative stress, insulin resistance, inflammation, and endothelial dysfunction are increased in OSA patients and microRNAs (miRs) are regulatory elements that influence these pathological mechanisms. miR125a, miR126, and miR146a-5p play a role in these pathological mechanisms and have not been evaluated in patients with OSA. METHOD: This case-control study was performed on 90 OSA patients and 34 controls. Circulating levels of miR125a, miR126, and miR146a-5 were determined using real-time PCR, and serum levels of hsCRP, ICAM-1, and VCAM-1 were evaluated using ELISA kits. RESULTS: miR125a and miR146a were elevated in patients with OSA compared to controls while miR126 decreased significantly. All three miRs indicated a remarkable difference between the mild-OSA group compared to the severe-OSA group. Furthermore, patients with OSA showed elevated levels of hsCRP, ICAM-1, and VCAM-1. Multiple linear regression indicated an independent association of miR125a with ICAM-1 and hsCRP, miR126 associated with VCAM-1 and total cholesterol, and miR146a-5p represented an association with apnea-hypopnea index and ICAM-1. Furthermore, miR146a-5p illustrated a good diagnostic ability to differentiate between OSA and controls. CONCLUSIONS: Circulating miR125a, miR126, and miR146a-5p fluctuations in patients with OSA and their relations with markers of endothelial dysfunction provide in vivo evidence and suggest a potential role for these miRs with endothelial dysfunction in patients with OSA.

Study of structural network connectivity using DTI tractography in insomnia disorder.

Most of tractography studies on insomnia disorder (ID) have reported decreased structural connectivity between cortical and subcortical structures. Tractography based on standard diffusion tensor imaging (DTI) can generate high number of false-positive streamlines connections between gray matter regions. In the present study, we employed the convex optimization modeling for microstructure informed tractography-2 (COMMIT2) to improve the accuracy of the reconstructed whole-brain connectome and filter implausible brain connections in 28 patients with ID and compared with 27 healthy controls. Then, we used NBS-predict (a prediction-based extension to the network-based statistic method) in the COMMIT2-weighted connectome. Our results revealed decreased structural connectivity between subregions of the left somatomotor, ventral attention, frontoparietal, dorsal attention and default mode networks in the insomnia group. Moreover, there is a negative correlation between sleep efficiency and structural connectivity within the left frontoparietal, visual, default mode network, limbic, dorsal attention, right dorsal attention as well as right default mode networks. By comparing with standard connectivity analysis, we showed that by removing of false-positive streamlines connections after COMMIT2 filtering, abnormal structural connectivity was reduced in patients with ID compared to controls. Our results demonstrate the importance of improving the accuracy of tractography for understanding structural connectivity networks in ID.

Discriminating Paradoxical and Psychophysiological Insomnia Based on Structural and Functional Brain Images: A Preliminary Machine Learning Study.

Insomnia disorder (ID) is a prevalent mental illness. Several behavioral and neuroimaging studies suggested that ID is a heterogenous condition with various subtypes. However, neurobiological alterations in different subtypes of ID are poorly understood. We aimed to assess whether unimodal and multimodal whole-brain neuroimaging measurements can discriminate two commonly described ID subtypes (i.e., paradoxical and psychophysiological insomnia) from each other and healthy subjects. We obtained T1-weighted images and resting-state fMRI from 34 patients with ID and 48 healthy controls. The outcome measures were grey matter volume, cortical thickness, amplitude of low-frequency fluctuation, degree centrality, and regional homogeneity. Subsequently, we applied support vector machines to classify subjects via unimodal and multimodal measures. The results of the multimodal classification were superior to those of unimodal approaches, i.e., we achieved 81% accuracy in separating psychophysiological vs. control, 87% for paradoxical vs. control, and 89% for paradoxical vs. psychophysiological insomnia. This preliminary study provides evidence that structural and functional brain data can help to distinguish two common subtypes of ID from each other and healthy subjects. These initial findings may stimulate further research to identify the underlying mechanism of each subtype and develop personalized treatments for ID in the future.

Controlling risky behavior associated with AIDS: the role of social support, family functioning, self-efficacy and AIDS risk perception.

OBJECTIVES: We believe that major steps can be taken towards Acquired Immunodeficiency Syndrome (AIDS) prevention through identifying the relevant factors that are apt to predict risky behavior. The main purpose of the present study was to analyze and evaluate the relationship of social support, family functioning, self-efficacy and AIDS risk perception to controlling risky behavior associated with AIDS. METHODS: To conduct this cross-sectional study, 765 subjects (59% female) were selected from the youth inhabiting the western provinces of Iran through cluster sampling. Five questionnaires were used: AIDS risk perception, self-efficacy in controlling risky behavior associated with AIDS, controlling risky behavior associated with AIDS, the multidimensional scale of perceived social support, and the family assessment device. RESULTS: The results demonstrated that all two models enjoyed acceptable fitness, and the mediating roles of self-efficacy and AIDS risk perception were confirmed. Moreover, family functioning and perceived social support together could predict 20% of the variance of controlling risky behavior associated with AIDS. The results also indicated that family functioning with a standardized coefficient of - 0.24 and self-efficacy in controlling risky behavior associated with AIDS with a standardized coefficient of 0.58 could predict the controlling risky behavior associated with AIDS (p < 0.01). CONCLUSIONS: Our findings suggest that self-efficacy and AIDS risk perception play major roles in controlling risky behavior associated with AIDS. Therefore, it is recommended that families and psychologists promote self-efficacy in order to prevent the occurrence of high-risk behaviors.

Asymmetric alterations of white matter integrity in patients with insomnia disorder.

Despite the adverse consequences of insomnia disorder for both individuals and society, the underlying neurobiological processes are poorly understood. The purpose was to further understand the alterations of white matter tracts in patients with insomnia and their association with sleep variables and also to determine if diffusion tensor imaging measures would be a useful disease marker. Twenty-six patients with insomnia and 26 age-matched healthy volunteers underwent diffusion tensor imaging. We employed an automated probabilistic tractography analysis approach using TRActs Constrained by UnderLying Anatomy (TRACULA) to quantify diffusion measures in major white matter tracts. We found significantly increased fractional anisotropy in the right cingulum-angular bundle and uncinate fasciculus in patients group compared to controls. Moreover, the mean diffusivity and radial diffusivity were reduced in the right cingulum-angular bundle in patients group in comparison with controls. We also found significantly increased fractional anisotropy along the bilateral cingulum-angular bundle and right uncinate fasciculus in patients. Also, mean and radial diffusivity were reduced along the right cingulum-angular bundle in patients group compared to controls. There is a significant positive correlation between fractional anisotropy and Epworth Sleepiness Scale scores. Moreover, there are negative correlations between mean, radial and axial diffusivity and total sleep time and sleep efficiency and also positive correlations between mean, radial and axial diffusivity and duration of disease and Pittsburgh Sleep Quality Index scores. This study showed the importance of examining whole-tract and waypoint white matter integrity in insomnia disorder. We found asymmetric widespread white matter integrity changes in patients with insomnia.

Alterations of Subcortical Brain Structures in Paradoxical and Psychophysiological Insomnia Disorder.

Insomnia disorder (ID) is a common illness associated with mood and cognitive impairments. Subtyping ID is an ongoing debate in sleep medicine, but the underlying mechanisms of each subtype is poorly understood. Growing evidence suggests that subcortical brain structures play the key roles in pathophysiology of ID and its subtypes. Here, we aimed to investigate structural alteration of subcortical regions in patients with two common ID subtypes i.e., paradoxical and psychophysiological insomnia. Fifty-five patients and 49 healthy controls were recruited for this study and T1-weighted images and subjective and objective sleep parameters (i.e., Pittsburgh Sleep Quality Index and polysomnography) were collected from participants. Subcortical structures including the hippocampus, amygdala, caudate, putamen, globus pallidus, nucleus accumbens, and thalamus were automatically segmented in FSL. Volume and shape (using surface vertices) of each structure were compared between the groups, controlled for covariates, and corrected for multiple comparisons. In addition, correlations of sleep parameters and surface vertices or volumes were calculated. The caudate's volume was smaller in patients than controls. Compared with controls, we found regional shrinkage in the caudate, nucleus accumbens, posterior putamen, hippocampus, thalamus, and amygdala in paradoxical insomnia and shrinkage in the amygdala, caudate, hippocampus, and putamen in psychophysiological insomnia. Interestingly, comparing two patients groups, shape alteration in the caudate, putamen, and nucleus accumbens in paradoxical insomnia and shrinkage in the thalamus, amygdala, and hippocampus in psychophysiological insomnia were observed. Both subjective and objective sleep parameters were associated with these regional shape alterations in patients. Our results support the differential role of subcortical brain structures in pathophysiology of paradoxical and psychophysiological insomnia.

Acceptance and Commitment Therapy (ACT) Improves Sleep Quality, Experiential Avoidance, and Emotion Regulation in Individuals with Insomnia-Results from a Randomized Interventional Study.

Insomnia is a common problem in the general population. To treat insomnia, medication therapies and insomnia-related cognitive-behavioral interventions are often applied. The aim of the present study was to investigate the influence of acceptance and commitment therapy (ACT) on sleep quality, dysfunctional sleep beliefs and attitudes, experiential avoidance, and acceptance of sleep problems in individuals with insomnia, compared to a control condition. A total of 35 participants with diagnosed insomnia (mean age: 41.46 years old; 62.9% females) were randomly assigned to the ACT intervention (weekly group therapy for 60-70 min) or to the active control condition (weekly group meetings for 60-70 min without interventional and psychotherapeutic character). At baseline and after eight weeks (end of the study), and again 12 weeks later at follow-up, participants completed self-rating questionnaires on sleep quality, dysfunctional beliefs and attitudes about sleep, emotion regulation, and experiential avoidance. Furthermore, participants in the intervention condition kept a weekly sleep log for eight consecutive weeks (micro-analysis). Every morning, participants completed the daily sleep log, which consisted of items regarding subjective sleep duration, sleep quality, and the feeling of being restored. Sleep quality, dysfunctional beliefs and attitudes towards sleep, emotion regulation, and experiential avoidance improved over time, but only in the ACT condition compared to the control condition. Improvements remained stable until follow-up. Improvements in experiential avoidance were related to a favorable change in sleep and cognitive-emotional processing. Micro-analyses showed that improvements occurred within the first three weeks of treatment. The pattern of results suggests that ACT appeared to have improved experiential avoidance, which in turn improved both sleep quality and sleep-related cognitive-emotional processes at longer-term in adults with insomnia.

The impact of continuous positive airway pressure therapy on circulating levels of malondialdehyde: a systematic review and meta-analysis.

BACKGROUND: Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder which associated with increased oxidative stress and cardiovascular diseases. Malondialdehyde (MDA) is a reliable marker of lipid peroxidation and is elevated in patients with OSA. Studies reported inconsistent findings on the effect of continuous positive airway pressure (CPAP) therapy on MDA levels. As the study power maybe a reason for the inconsistent findings, we aimed to use meta-analysis to assess effect of CPAP therapy on MDA in patients with OSA. METHOD: Electronic search was performed to find out studies on the effect of CAPA on MDA levels in OSA patients. Search carried out in databases of PubMed, EMBASE, Scopus, Cochrane library and web of science. RESULTS: Search resulted in 161 records of which 83 remained after removing duplicated records. Further, 51 articles were removed by title and abstract and 22 records evaluated by full text. Finally 13 articles were included in the intended meta-analysis. Pooled analysis demonstrated that CPAP therapy reduced MDA levels significantly [SMD (-1.51) (95% CI, -2.06 to -0.97) p < 0.05]. Subgroup analyses showed that CPAP therapy was effective in categories of age (≤50 and > 50 years), BMI (≤30 and > 30 kg/m2) and therapy duration (≤12 week and >12 week). CONCLUSION: the results of the present study demonstrated considerable effect of CPAP therapy on MDA as independent risk factor for cardiovascular diseases and robust marker of lipid peroxidation.

White matter alterations in patients with obstructive sleep apnea: a systematic review of diffusion MRI studies.

BACKGROUND: Obstructive sleep apnea (OSA) is a common sleep disorder, which causes wide range of neurological and psychiatric symptoms. Several studies demonstrated structural and functional brain alterations using magnetic resonance imaging (MRI) techniques. Recently, diffusion-based brain MRI studies in patients with OSA showed changes in diffusion measures that represent various impairments of white matter (WM) integrity. The various finding may be due to diffusion indices employed for detection of neural impairment at the microstructural level, phase of the disease and the goals of studies. OBJECTIVES: We aimed to identify a common abnormal WM pattern across the previous studies. METHODS: We reviewed related literature in EMBASE, Scopus and PubMed databases and identified 13 studies that meet our selection criteria. RESULTS: The current data pointed to WM integrity changes in corpus callosum, cingulate cortex, corticospinal tract, insular cortex, basal ganglia, and limbic sites. These regions mainly contribute in mood, autonomic and cardiovascular regulation. CONCLUSION: Widespread use of diffusion magnetic resonance imaging (dMRI) parameters provides insight into the pathophysiology of OSA, stage of the disease and planning appropriate treatments in future.

Role of CA1 GABAA and GABAB receptors on learning deficit induced by D-AP5 in passive avoidance step-through task.

To investigate the interaction between hippocampal γ-aminobutyric acid GABAA receptor (GABAAR) or GABAB receptor (GABABR) and N-methyl-D-aspartate receptor (NMDAR) in the acquisition of passive avoidance memory in rats, we used GABAA or GABAB agents, D-AP5 (as a NMDAR antagonist), and a combination of the mentioned drugs in a step-through task. All agents were microinjected into the intra-CA1 regions at a volume of 1 µl/rat, prior to training. GABAAR agonist muscimol (0.2 µg/rat), selective GABABR agonist baclofen (0.5 µg/rat) or NMDAR antagonist D-AP5 (0.25 µg/rat) decreased step-through latency, indicating a memory retention impairment. Neither GABAAR antagonist bicuculline (0.0625-0.25 µg/rat) nor GABABR antagonist phaclofen (0.1-0.5 µg/rat) altered memory retrieval by itself. Moreover, the lower dose of muscimol (0.05 µg/rat) decreased D-AP5 (0.125 µg/rat) response on memory acquisition, but bicuculline did not alter the D-AP5 response. Furthermore, baclofen and phaclofen at the dose of 0.1 µg/rat potentiated D-AP5 response at the doses of 0.0625 and 0.125 µg/rat, but abolished memory impairment induced by D-AP5 at the higher dose (0.25 µg/rat). The results suggest that the microinjection of GABAA and GABAB agents into the CA1 region differently affects memory acquisition deficit induced by D-AP5. The activation of GABAARs increased the impairment effect of D-AP5 on passive avoidance memory, but their blockade did not have an effect. Also, the activation or blockade of GABABRs induced a similar and dual effect.