Research paperResidual depressive symptoms, sleep disturbance and perceived cognitive impairment as determinants of functioning in patients with bipolar disorder
Introduction
Bipolar disorder (BD) is a severe and highly recurrent mental illness affecting more than one per cent of the world's population (Grande et al., 2016, Merikangas et al., 2011). A substantial proportion of BD patients (30–60%) are living with significant functional impairment even after reaching clinical remission (MacQueen et al., 2001). According to the World Health Organisation, BD is among the leading causes of years lost due to disability (WHO, 2008).
The inter-episode period (also named euthymia) was regarded as an asymptomatic phase in which BD patients were in clinical remission. However, this classical perspective has been challenged since a large number of euthymic patients experience residual symptoms during periods of apparent clinical stability (Soreca et al., 2009). New evidence suggests that BD is not only a recurrent mental illness but also a chronic disease associated with the persistence of residual symptoms shaping an individual presentation. Several studies have shown the persistence of depressive symptoms (Judd et al., 2003), cognitive impairments (Bourne et al., 2013, Mann-Wrobel et al., 2011), sleep and circadian rhythm disturbances (Geoffroy et al., 2014, Mondin et al., 2016, Sylvia et al., 2012) and emotional dysregulation (Strejilevich et al., 2013) in euthymic BD patients. Interestingly, residual symptoms appear to impact the natural course of BD and represent potential predictors of long-term outcome. Residual depressive symptoms are associated with an increased risk of recurrence (de Dios et al., 2012, Judd et al., 2008) and, together with persistent cognitive deficits and sleep disturbances, are important predictors of functional impairment (Altshuler et al., 2006, Bas et al., 2015, Baune and Malhi, 2015, Bonnín et al., 2010, Dittmann et al., 2008, Gitlin and Miklowitz, 2016, Harvey et al., 2005, Marangell et al., 2009, Pinho et al., 2015, Rosa et al., 2010, Wingo et al., 2009, Wingo et al., 2010).
Moreover, an interaction between those residual symptoms may exist—e.g. residual depressive symptoms seem to worsen cognitive deficits, producing a subsequent negative impact on functioning (Bonnín et al., 2014), or poor sleep and cognitive functioning seem to be associated with poor work performance (Boland et al., 2015). However, the exact nature of the interdependent relationships among residual depressive symptoms, cognitive impairment, sleep disturbances and functioning, and the relative contribution of each of these residual symptoms, remains unclear.
The observational OPTHYMUM study aimed to examine residual symptoms in BD patients who were recruited in the euthymic period. Previous analyses showed that residual symptoms (mainly residual depressive symptoms, perceived cognitive impairment and sleep disturbances) have an impact on functioning (Samalin et al., 2014, Samalin et al., 2016a) and their severity seems to be negatively related to the duration of the euthymia (Samalin et al., 2016b). However, these previous reports did not examine the direction and the structure of the relationships between residual symptoms and functioning. It would be of interest to contribute to a better understanding of the negative impact of these residual symptoms on the functioning of BD patients and it could have implications for its improvement.
Based on previous research (Boland and Alloy, 2013, Bonnín et al., 2012, Bonnín et al., 2014, Bowie et al., 2010, Giglio et al., 2010, Gruber et al., 2009, Leboyer and Kupfer, 2010, Rosa et al., 2013, Russo et al., 2015, Volkert et al., 2015), our hypotheses were that: i) residual depressive symptoms and perceived cognitive performance primarily have a direct effect on functioning; ii) sleep disturbances have an indirect effect on functioning via perceived cognitive performance and residual depressive symptoms; iii) residual depressive symptoms might have a moderate indirect effect on functioning via perceived cognitive performance; and iv) sleep disturbances might have a moderate direct effect on functioning.
The aim of the present study was to examine a comprehensive model based on structural equation modelling (SEM) that integrates the interrelationships between residual depressive symptoms, sleep disturbances and self-reported cognitive impairment as determinants of psychosocial functioning in a sample of euthymic BD patients in real-life conditions.
Section snippets
Study participants
This study is based on a sample of 468 adult outpatients with BD from a multi-centre, cross-sectional, non-interventional study conducted in France between April and October 2012 (Samalin et al., 2014).
An enlarged directory of psychiatrists randomly assigned from a previous French study on bipolar disorder was used (Nuss et al., 2012) to recruit a large number of patients. A total of 139 French psychiatrists in hospital and office-based settings agreed to participate to the study.
The inclusion
Sample characteristics
The sample consisted of 468 euthymic BD patients. Sociodemographic, clinical, functioning and therapeutic characteristics of the sample are presented in Table 1. Mean age was 47.7±12.5 years and 41% (n=192) were male. Mean age at onset of BD was 29.3±10.8 years, and most of the patients had a predominant depressive polarity of BD (56.6%).
Correlations
Correlations are provided in Table 2.
Residual depressive symptoms were moderately associated with all functioning domains except occupational functioning (r
Discussion
The present study investigated, through a SEM approach, the influence of residual depressive symptoms, perceived cognitive performance and sleep disturbances on psychosocial functioning among euthymic BD patients in real-life conditions. This is the first study to explore these three residual symptoms in the same model as determinants of functioning in BD. Our results highlight the non-straightforward relationship between sleep disturbances and functioning. The model showed good fit with the
Conclusion
This study highlights that residual depressive symptoms and perceived cognitive performance have a direct impact on the functioning of BD patients during the inter-episodic period. Sleep disturbances also seem to be associated with functional impairment, but only indirectly. The systematic assessment of residual symptoms based on easily administered questionnaires (e.g. self-evaluation of cognitive performance, sleep quality and sleep disturbance questionnaire) appears feasible and necessary in
Role of funding sources
This study was supported by Bristol-Myers Squibb France and Otsuka Pharmaceuticals France SAS. The funders had no further role in design study, data collection analysis and interpretation, writing of the report, and the decision to submit the paper for publication.
Contributors
PML and FB designed the study. LS, PML and FB performed the experiments. LB, LS and MB performed statistical analysis of results. LS, AM, FB, PML and EV wrote the first draft of the manuscript. All authors (LS, LB, AM, IP, MR, CMB, CT, NV, CP, IdC, MB, PAG, FB, PML, EV) contributed to and have approved the final manuscript.
Acknowledgements
We are greatly indebted to the many people who gave their time to participate in this study (Rosine Arnaud, Nabil Bedira, Anne Dillenschneider, Anne Filipovics, Pierre Vekoff and the investigators).
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