For over two decades clinical studies have been conducted which suggest the existence of a relationship between depression and Obstructive Sleep Apnea (OSA). Recently, Ohayon underscored the evidence for a link between these two disorders in the general population, showing that 800 out of 100,000 individuals had both, a breathing-related sleep disorder and a major depressive disorder, with up to 20% of the subjects presenting with one of these disorders also having the other. In some populations, depending on age, gender and other demographic and health characteristics, the prevalence of both disorders may be even higher: OSA may affect more than 50% of individuals over the age of 65, and significant depressive symptoms may be present in as many as 26% of a community-dwelling population of older adults. In clinical practice, the presence of depressive symptomatology is often considered in patients with OSA, and may be accounted for and followed-up when considering treatment approaches and response to treatment. On the other hand, sleep problems and specifically OSA are rarely assessed on a regular basis in patients with a depressive disorder. However, OSA might not only be associated with a depressive syndrome, but its presence may also be responsible for failure to respond to appropriate pharmacological treatment. Furthermore, an undiagnosed OSA might be exacerbated by adjunct treatments to antidepressant medications, such as benzodiazepines. Increased awareness of the relationship between depression and OSA might significantly improve diagnostic accuracy as well as treatment outcome for both disorders. In this review, we will summarize important findings in the current literature regarding the association between depression and OSA, and the possible mechanisms by which both disorders interact. Implications for clinical practice will be discussed.

/pdf/depression-and-obstructive-sleep-apnea-osa-1k0lwn107q.pdf

Depression and Obstructive Sleep Apnea (OSA)

Study Objectives: We conducted the present study to determine whether psychiatric disorders are commonly associated with sleep apnea in Veterans Health Administration beneficiaries. Method: The Veterans Health Administration maintains several centralized databases containing healthcare data for more than 4 million veterans. We reviewed data from 1998 to 2001 and identified patient records having International Classification of Diseases-Ninth Edition-Clinical Modification codes indicating sleep apnea and various psychiatric conditions. Subsequently, we compared age, sex, ethnicity, and prevalence of comorbid psychiatric conditions for Veterans Health Administration beneficiaries with and without sleep apnea. Results: Out of 4,060,504 unique cases, 118,105 were identified as having sleep apnea (estimated prevalence of 2.91%). Mean age at the time of diagnosis was 57.6 years. Psychiatric comorbid diagnoses in the sleep apnea group included depression (21.8%), anxiety (16.7%), posttraumatic stress disorder (11.9%), psychosis (5.1), and bipolar disorders (3.3%). Compared with patients not diagnosed with sleep apnea, a significantly greater prevalence (P < .0001) was found for mood disorders, anxiety, posttraumatic stress disorder, psychosis, and dementia in patients with sleep apnea. Conclusions: Sleep apnea is associated with a higher prevalence of psychiatric comorbid conditions in Veterans Health Administration beneficiaries. This association suggests that patients with psychiatric disorders and coincident symptoms suggesting sleep-disordered breathing should be evaluated for sleep apnea.

/pdf/association-of-psychiatric-disorders-and-sleep-apnea-in-a-3vvf3b0c5g.pdf

Association of psychiatric disorders and sleep apnea in a large cohort.

Background Sleep-related breathing disorder (SRBD) and depression have each been independently associated with substantial morbidity, impairment, and disability. The development of clinical strategies for screening and managing depression in patients with SRBD requires elucidation of the association between the 2 conditions. This population-based epidemiological study assesses SRBD as a longitudinal predictor of depression. Methods Men (n = 788) and women (n = 620) randomly selected from a working population were evaluated for SRBD by in-laboratory polysomnography and for depression by the Zung depression scale. Results of multiple studies, performed at 4-year intervals, were available for most participants. Sleep-related breathing disorder was characterized by the apnea-hypopnea index (AHI; events per hour) categories: AHI = 0, no SRBD; 0 Results In purely longitudinal models, an increase of 1 SRBD category (eg, from minimal to mild SRBD) was associated with a 1.8-fold (95% confidence interval, 1.3-2.6) increased adjusted odds for development of depression. In adjusted models combining longitudinal and cross-sectional associations, compared with participants with no SRBD, the odds for development of depression were increased by 1.6-fold (95% confidence interval, 1.2-2.1) in participants with minimal SRBD, by 2.0-fold (95% confidence interval, 1.4-2.9) in participants with mild SRBD, and by 2.6-fold (95% confidence interval, 1.7-3.9) in those with moderate or worse SRBD. Conclusion Our longitudinal findings of a dose-response association between SRBD and depression provide evidence consistent with a causal link between these conditions and should heighten clinical suspicion of depression in patients with SRBD.

/pdf/longitudinal-association-of-sleep-related-breathing-disorder-8g9ch0m74m.pdf

Longitudinal Association of Sleep-Related Breathing Disorder and Depression

Obstructive sleep apnea and depression

Background: Obstructive sleep apnea (OSA) has been associated with mental disorders, but the strength of this association is unknown. The aim of our study was to investigate the association among OSA, depression, and anxiety in adults and to quantitatively summarize the results. Methods: A literature search in Medline, PubMed, PsycInfo, Scopus, and Web of Science was conducted. Seventy-three articles were selected for study. Results: The pooled prevalence of depressive and anxious symptoms in OSA patients was 35% (95% CI, 28-41%) and 32% (95% CI, 22-42%), respectively. Conclusions: The association between OSA, anxiety, and depression indicates the value of an early diagnosis and personalized treatment of OSA to improve mental disorders conditioning compliance to therapy. These conditions share a probably bidirectional relationship.

Association of Anxiety and Depression in Obstructive Sleep Apnea Patients: A Systematic Review and Meta-Analysis.

Background Previous studies have shown that patients with systemic lupus erythematosus (SLE) tend to have a higher risk of cardiovascular disease (CVD), but the potential causal relationship between genetic susceptibility to SLE and CVD risk is not clear. This study systematically investigated the potential association between genetically determined SLE and the risk of CVD. Methods The genetic tools were obtained from genome-wide association studies of SLE and CVD, with no overlap between their participating populations. Mendelian randomization (MR) analysis was performed using inverse variance weighting as the primary method. Simultaneously, a series of repeated analyses, sensitivity analyses, and instrumental variable strength evaluations were performed to verify the reliability of our results. Results MR analysis showed that genetic susceptibility to SLE was associated with a higher risk of heart failure (OR=1.025, 95% CI [1.009-1.041], P=0.002), ischemic stroke (OR=1.020, 95% CI [1.005-1.034], P=0.009), and venous thromboembolism (OR=1.001, 95% CI [1.000-1.002], P=0.014). However, genetic susceptibility to SLE was negatively correlated with the risk of type 2 diabetes (OR=0.968, 95% CI [0.947-0.990], P=0.004). Sensitivity analysis found no evidence of horizontal pleiotropy or heterogeneity. Conclusion Our MR study explored the causal role of SLE in the etiology of CVD, which would help improve our understanding of the basic disease mechanisms of SLE and provide comprehensive CVD assessment and treatment for SLE patients.

/pdf/systemic-lupus-erythematosus-and-cardiovascular-disease-a-rvqwueh9.pdf

Systemic Lupus Erythematosus and Cardiovascular Disease: A Mendelian Randomization Study

Background A large number of observational studies showed that patients with psoriasis have a higher risk of cardiovascular disease (CVD), but most studies did not fully adjust for confounding factors, so it is not clear whether the risk of CVD is directly attributed to psoriasis. We used Mendelian randomization (MR) to evaluate the potential causal relationship between psoriasis and CVD. Methods We used genetic instruments from the genome-wide association study (GWAS) of European descent for psoriasis to investigate its relationship with CVD. Inverse variance-weighted (IVW) MR analyses were used for the primary analysis. In addition, a variety of other methods were used to replicate the analysis. Results The fixed-effects IVW method indicated that genetic susceptibility to psoriasis was associated with a higher risk of heart failure (HF) [odds ratio (OR) = 1.04; 95% CI, 1.01–1.06, P = 2.72E-03], atrial fibrillation (AF) (OR = 1.04; 95% CI, 1.02–1.07, P = 3.27E-04), myocardial infarction (MI) (OR = 1.07; 95% CI, 1.01–1.12, P = 0.01), valvular heart disease (VHD) (OR = 1.001; 95% CI, 1.000–1.002, P = 1.85E-03), and large artery stroke (LAS) (OR = 1.11; 95% CI, 1.05–1.18, P = 5.37E-04) but not with the other two subtypes of ischemic stroke (IS) [cardioembolic stroke (CES) (OR = 1.03; 95% CI, 0.98–1.07, P = 0.27) and small vessel stroke (SVS) (OR = 1.00; 95% CI, 0.95–1.07), P = 0.88)]. Sensitivity analysis found weak evidence of horizontal diversity and heterogeneity to ensure the stability of the results. Conclusion Our study provided evidence for a potential causal link between psoriasis and CVD. These findings partly suggest that early monitoring of cardiovascular risk in patients with psoriasis is intentional.

The Association Between Psoriasis and Risk of Cardiovascular Disease: A Mendelian Randomization Analysis

Background Although studies suggest that tea consumption is associated with a reduced risk of cardiovascular disease (CVD). There is no unified conclusion about the potential relationship between tea drinking and CVD. We used a two-sample Mendelian randomized (MR) analysis to systematically explore the causal relationship between tea intake and CVD subtypes for the first time. Furthermore the mediating effect of hypertension was also explored by a two-step MR. Methods Genetic instruments for tea intake were identified from a genome-wide association studies (GWAS) involving 447,485 people. Summary data on cardio-vascular disease came from different GWAS meta-analysis studies. In the first step we explored the causal effect of tea intake and CVD. In the second step, we examined the association of hypertension with heart failure and ischemic stroke and estimated the mediating effect of hypertension. Inverse variance weighted MR analysis was used as the primary method for causal analysis. A further sensitivity analysis was performed to ensure robustness of the results. Results One standard deviation increase in tea intake was associated with a 25% (OR = 0.75, 95%CI = 0.61–0.91, p = 0.003) lower risk of hypertension, a 28% (OR = 0.72, 95%CI = 0.58–0.89, p = 0.002) lower risk of heart failure, and a 29% (OR = 0.71, 95%CI = 0.55–0.92, p = 0.008) lower risk of ischemic stroke, respectively. And the association between tea drinking and the risk of heart failure and ischemic stroke may be mediated by hypertension. Sensitivity analyses found little evidence of pleiotropy. Conclusion Our two-sample MR analysis provided genetic evidence that tea intake was significantly associated with a reduced risk of hypertension, heart failure, and ischemic stroke, and that hypertension may be a potential mediator. Further large randomized controlled trials should be conducted to confirm the causal effect of tea consumption on cardiovascular disease risk.

/pdf/causal-relationship-between-tea-intake-and-cardiovascular-2kfxstqk.pdf

Causal relationship between tea intake and cardiovascular diseases: A Mendelian randomization study

OBJECTIVE To identify polymorphisms of the serotonin transporter(5-HTT) gene and to find out whether there was relationship between any such polymorphisms and sleep apnea syndrome (SAS) METHODS For two polymorphisms of 5-HTT target DNA gene was amplified using polymerase chain reaction (PCR) and 6% non-denaturing polyacrylamide gels electrophoresis The frequencies of the different forms of the genotypes and alleles of 5-HTT gene were analyzed in 104 patients with SAS and 150 healthy controls RESULTS The frequencies of the S or L alleles and the S/S, S/L or L/L genotypes in promoter region of 5-HTT gene in SAS group were not significantly different to those in healthy controls (P > 005) However, the frequencies of 10/10, 12/10 genotypes of 5-HTT-VNTR in SAS patients were significantly higher than those in healthy control subjects (P < 005) Moreover, the frequency of the allele 10 of 5-HTT-VNTR in SAS patients was significantly higher than that in healthy controls (P<001) CONCLUSION The allele 10 of 5-HTT-VNTR might be a susceptible factor in the pathogenesis of SAS

Association study of sleep apnea syndrome and polymorphisms in the serotonin transporter gene

Background Although studies suggest that concentrations of serum 25-hydroxyvitamin D (25(OH)D) are lower in individuals with Heart Failure (HF), the beneficial effects of vitamin D supplementation are controversial. Therefore, in this study, we aimed to determine whether there is a causal relationship between serum Vitamin D (VD) levels and HF. Methods We obtained genetic instruments from the largest available genome-wide association study (GWAS) of European descent for 25(OH)D (443, 734 individuals) to investigate the association with HF (47,309 cases, 930,014 controls), and vice versa. Two-sample bidirectional Mendelian Randomization (MR) analysis was performed to infer the causality. In addition to the primary analysis using inverse variance-weighted (IVW) MR, we applied five additional methods to control for pleiotropy [MR-Egger, weighted median, Maximum-likelihood, MR-robust adjusted profile score (MR-RAPS) and MR-pleiotropy residual sum and outlier (MR-PRESSO)] and compared their respective MR estimates. We also performed a sensitivity analysis to ensure that our results were robust. Results Mendelian randomized analysis showed that increased serum 25(OH)D was associated with a lower risk of HF in the IVW method (odds ratio [OR] = 0. 81;95%CI, 0.70–0.94, P = 0.006). In the reverse MR analyses, the genetic predisposition to HF was negatively correlated with serum 25(OH)D level (OR = 0. 89;95%CI, (0.82–0.97), P = 0.009). Conclusion Our study revealed the possible causal role of 25(OH)D on decreasing the risk for HF. Meanwhile, reverse MR analysis suggested that HF may be associated with lower vitamin D levels, it could be the potential implications for dietary recommendations.

/pdf/associations-between-vitamin-d-levels-and-risk-of-heart-1wkbg592.pdf

Associations Between Vitamin D Levels and Risk of Heart Failure: A Bidirectional Mendelian Randomization Study

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