Clinical characteristics of obstructive sleep apnea in bipolar disorders

Highlights

• High prevalence of OSA risk (22%) in a European population of remitted BD patients.

• OSA is associated with cardiovascular diseases, more refractory and severe BD.

• Both subjective and objective sleep abnormalities are associated with OSA.

• Higher BMI and residual depressive symptoms are the two best independent predictors.

• Sleepiness, languid type, and a higher fragmentation index help predicting OSA.

Abstract

Background

Obstructive sleep apnea (OSA) is one of the leading non-psychiatric comorbidities in bipolar disorders (BD). We sought to explore associations between risk of OSA in BD, clinical characteristics alongside with both subjective sleep complaints and objective sleep abnormalities.

Methods

Euthymic patients with BD (n = 144) were assessed over a three-week period, by actigraphy, clinical interviews and questionnaires.

Results

Of the study sample, 32 (22%) individuals were at high risk of OSA (HR-OSA) and 112 (78%) had a low risk (LR-OSA), as assessed with the Berlin questionnaire. HR-OSA, compared to LR-OSA, were older (p = 0.031), had higher BMI (p < 0.0005), larger neck circumference (p = 0.002), and more residual depressive symptoms (p < 0.0005). HR-OSA was also associated with greater sleepiness (p = 0.003), poorer sleep quality (p = 0.003), insomnia complaints (p = 0.027), “languid” chronotype (p = 0.002), and higher actigraphy-derived fragmentation index (p = 0.015). Backward stepwise linear regression retained BMI and depressive symptoms (correct classification of 83% of participants). Classification increased up to 85.4% when adding sleepiness and languid-vigorous scales and up to 87.8% when adding fragmentation index. Combining ROC curve analysis and Youden Index provided best cut-offs (HR-OSA if cut-off greater than or equal to) of 29.84 for BMI (Sensibility(Se) = 0.47, Specificity(Spe) = 0.96) and 1.5 for MADRS total score (Se = 0.84, Spe = 0.58).

Limitations

No confirmation of OSA diagnosis with polysomnography.

Conclusions

Higher BMI and residual depressive symptoms are the two best independent predictors of OSA in BD. Such information contributes to improving the screening and management of OSA in BD.

Trial Number

NCT02627404.

Introduction

Worldwide, approximately 1% to 4% of people suffer from bipolar disorder (BD). BD is a severe mental disorder ranking as the fourth most important contributor to the global disease burden among psychiatric, neurological and substance-use disorders (Collins et al., 2011, Merikangas et al., 2007). Whereas BD has traditionally been defined by recurrences of manic and depressive episodes, it is now recognized that BD patients also present with persistent abnormalities between mood episodes (such as cognitive deficits, cardio-vascular diseases, altered sleep homeostasis and circadian dysregulation), leading to conceptualizations of BD as a chronic and multisystem disorder (Leboyer et al., 2012). BD is associated with a 10–20 years decrease in life expectancy, which has not improved over recent decades, unlike the increased longevity has seen in the general population (Chesney et al., 2014, Hayes et al., 2015). This premature mortality is partly explained by high levels of suicide, as well as the consequences of non-psychiatric comorbidities (Hayes et al., 2015). Obstructive sleep apnea (OSA) is one of the leading non-psychiatric comorbidities in BD, with a prevalence estimated at 24.5% in a recent meta-analysis (Stubbs et al., 2016). OSA is a sleep disorder characterized by recurrent airflow obstructions, which increase the risk of hypertension, coronary artery disease, arrhythmias, heart failure, and stroke (Bradley and Floras, 2009, Lévy et al., 2015). Decreased life expectancy in BD is also closely linked to the high prevalence of such cardiovascular diseases (Baune et al., 2006, Martin et al., 2016), and associated metabolic syndrome (Geoffroy et al., 2017, Godin et al., 2014, Vancampfort et al., 2015). There is therefore a considerable overlap in the co-occurrence of cardiovascular disorders in OSA and BD. Of note, cardiovascular disorders are the most important contributors to premature death in BD patients (Hayes et al., 2015). OSA has a deleterious impact on quality of life, partly arising from sleep fragmentation, which can lead to reduced neurocognitive function and increased risk of motor vehicle and occupational accidents (Malhotra and White, 2002). OSA may also contribute to the decreased response to pharmaceutical mood treatments (Schröder and O'Hara, 2005), and to modulate clinical features in BD patients, which was first indicated in a study by Soreca et al. (2012). In a study of 72 individuals with BD I subtype, those at high risk for OSA, as assessed with the Berlin questionnaire, scored significantly higher on measures of both depression and mania (Soreca et al., 2012). Given the potentially harmful effects of sleep fragmentation on mood symptoms and the substantial overlap of symptomatology in OSA and BD (Altena et al., 2016), this is an important area for further study, especially the associated features of OSA in BD patients and their management implications (Gupta and Simpson, 2015, Kelly et al., 2013, Stubbs et al., 2016). In this study, a large, well-characterized clinical sample of 144 remitted BD cases, at low and high risk of OSA are compared using both questionnaires and actigraphy.