The association between insomnia-related sleep disruptions and cognitive dysfunction during the inter-episode phase of bipolar disorder
Introduction
Bipolar disorder is one of the 10 most disabling conditions worldwide (World Health Organization, 2001) and has a lifetime prevalence ranging from 0.4 to 2.4% (Merikangas et al., 2011). Individuals with bipolar disorder continue to experience substantial impairment during periods identified as neither depressive nor manic, a phase referred to as the inter-episode phase (Judd et al., 2003, MacQueen et al., 2003, Robb et al., 1997). Sleep disturbance and cognitive dysfunction (World Health Organization, 2001) are two important domains of impairment during the inter-episode phase, each contributing to functional impairment and reduced quality of life (e.g., Harvey et al., 2005, Robinson et al., 2006). Despite considerable literature demonstrating a link between sleep and cognition in healthy and sleep-disordered samples, the association between sleep and cognition remains under-examined in inter-episode bipolar disorder.
Seventy percent of individuals with bipolar disorder report clinically significant sleep problems during the inter-episode phase (Harvey et al., 2005) and over half (55%) meet diagnostic criteria for insomnia (Harvey et al., 2005). Insomnia is defined by subjective difficulty falling asleep, staying asleep, or waking up too early, despite adequate opportunity to sleep, with associated daytime impairment or distress (American Psychiatric Association, 2013). Insomnia is also associated with short sleep duration (Vgontzas et al., 2009, Vgontzas et al., 2010) and night-to-night variability in sleep behaviors (Buysse et al., 2010, Frankel et al., 1976). Fragmented sleep, shortened sleep duration, and elevated variability in sleep behaviors are also observed during inter-episode bipolar disorder, regardless of insomnia diagnosis (Eidelman et al., 2010, Geoffroy et al., 2014, Gruber et al., 2009, Jones et al., 2005, Kanady et al., 2015, Millar et al., 2004, Ritter et al., 2012).
Cognitive dysfunction is also common during inter-episode bipolar disorder. Although many cognitive processes are impaired during the inter-episode phase, some of the largest effect sizes have been found for performance on tasks of working memory (Robinson et al., 2006) and verbal learning (Robinson et al., 2006). Working memory is a system for temporarily storing and managing information so that it is easily accessible and can be utilized to carry out a task (Baddeley, 1992). Verbal learning is the process of acquiring, retaining, and recalling verbal material (Ausubel, 1963).
Previous research has demonstrated a relationship between sleep disruption and cognitive dysfunction in healthy and insomnia samples. In healthy populations, sleep deprivation prior to learning is associated with a 40% reduction in the ability to learn new material (Yoo et al., 2007) and impairs performance across a variety of tasks including working memory (Alhola and Polo-Kantola, 2007, Chee and Choo, 2004, Lim and Dinges, 2010) and verbal learning (e.g., Drummond et al., 2000). Some studies report that insomnia is associated with objective cognitive dysfunction (Edinger et al., 2009, Schneider et al., 2004, Varkevisser and Kerkhof, 2005, Varkevisser et al., 2007) while other studies reveal no such relation (Orff et al., 2007, Varkevisser et al., 2007). Mixed findings may be due to specific insomnia-related sleep disruptions underlying associations with cognition. Indeed, greater wake after sleep onset (Blackwell et al., 2006, Blackwell et al., 2014, Naismith et al., 2010, Wilckens et al., 2016) and longer sleep onset latency (Blackwell et al., 2006, Luik et al., 2015) are associated with greater cognitive deficits in older adults. Insomnia coupled with short sleep duration (<6 h) also appears to have a greater impact on cognitive dysfunction when compared to insomnia with normal sleep duration and healthy sleep patterns (Fernandez-Mendoza et al., 2010). Only one study has examined the impact of sleep variability on cognition (McCrae et al., 2012), revealing that night-to-night variability in sleep duration and total wake time did not predict performance on a processing speed or an executive functioning task in older adults.
Despite the evidence demonstrating an association between sleep and cognition in healthy and insomnia samples, the potential contribution of sleep disturbance to inter-individual variation in cognitive dysfunction during inter-episode bipolar disorder is under-characterized (see Boland and Alloy, 2013 for a review). Using a depression scale, one study demonstrated that individuals with bipolar disorder who demonstrate poorer cognitive performance on a neuropsychological battery report higher rates of insomnia compared to individuals with bipolar disorder who demonstrate intact cognitive performance (Volkert et al., 2015). Using post-hoc exploratory correlational analyses, a second study demonstrated an association between the Pittsburgh Sleep Quality Index (PSQI; Buysse et al., 1989) rated daytime dysfunction and a working memory task (Boland et al., 2015). Another study demonstrated that poorer performance on measures of working memory, visual learning, and social cognition was associated with patient ratings of poor sleep quality and increased daytime sleepiness (Russo et al., 2015).
The objective of the present study was to examine the association between sleep and cognition during inter-episode bipolar disorder using standard measurement methods and a therapeutic manipulation of sleep. The first aim was to examine whether insomnia diagnosis and subjective insomnia-related sleep disruptions – in particular total wake time (TWT), total sleep time (TST), total wake time variability (TWTvar), and total sleep time variability (TSTvar) – have an independent or interactive effect on working memory and verbal learning performance during the inter-episode phase. Based on the mixed findings of previous research, we tested two competing hypotheses: (1) there would be a main effect of insomnia diagnosis and an interactive effect whereby insomnia diagnosis and greater subjective TWT, shorter TST, greater TWTvar, and/or greater TSTvar in the insomnia group would predict poorer cognitive performance, versus (2) greater TWT, shorter TST, greater TWTvar, and/or greater TSTvar would independently predict poorer cognitive performance, regardless of insomnia diagnosis.
The second aim was to determine if working memory and verbal learning performance improves following a form of cognitive behavior therapy for insomnia modified specifically for bipolar disorder (CBTI-BD; Harvey et al., 2015). We hypothesized that participants with bipolar disorder who demonstrated an improvement in the subjective sleep parameters of interest (i.e., TWT, TST, TWTvar, and TSTvar) following CBTI-BD would show a related improvement in cognitive performance relative to a control psychoeducation treatment condition.
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Participants
Forty-seven adults with bipolar disorder and a comorbid insomnia diagnosis (BD-Insomnia) and 19 adults with bipolar disorder without sleep disturbance in the last six months (BD-Control) participated in the study. Individuals were eligible if they (a) met DSM-IV-TR criteria (American Psychiatric Association, 2000) for bipolar disorder, type I; (b) were inter-episode as defined by a score of 24 or less on the Inventory of Depressive Symptomatology, Clinician Rating (IDS-C; Rush et al., 1996), a
Demographic, clinical, and sleep characteristics
Participant characteristics are reported in Table 1. The two groups did not differ on any demographic characteristic with the exception of age; the BD-Control group was significantly younger than the BD-Insomnia group (p < 0.01). No significant group differences were observed for manic symptom severity (YMRS), duration of bipolar disorder, or number of lifetime mood episodes. The BD-Insomnia group reported greater depressive symptom severity (IDS-C, p < 0.05). The BD-Insomnia group also
Discussion
The overarching goal of the present study was to examine the impact of insomnia diagnosis and subjective insomnia-related sleep disruptions on working memory and verbal learning performance during inter-episode bipolar disorder. Results from the first aim demonstrated a main effect of TSTvar. More specifically, greater TSTvar predicted poorer working memory and verbal learning performance, regardless of insomnia diagnosis. Insomnia diagnosis did not predict working memory or verbal learning
Role of funding source
This project was supported by a National Institute of Mental Health Grant No. R34MH080958 awarded to AGH.
Contributions
All authors were involved in the conception, drafting and final approval of this manuscript.
Acknowledgements
The authors would like to thank Jason Lee, Jillian Tessier, and Anita Satish for their contributions to data collection, Jillian Tessier for her contribution to the literature search, and Kerrie Hein for her continued support throughout the study.
References (76)
- et al.
Validation of the Insomnia Severity Index as an outcome measure for insomnia research
Sleep. Med.
(2001) - et al.
Sleep disturbance and cognitive deficits in bipolar disorder: toward an integrated examination of disorder maintenance and functional impairment
Clin. Psychol. Rev.
(2013) - et al.
Associations between sleep disturbance, cognitive functioning and work disability in Bipolar Disorder
Psychiatry Res.
(2015) - et al.
Night-to-night sleep variability in older adults with and without chronic insomnia
Sleep. Med.
(2010) - et al.
The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research
Psychiatry Res.
(1989) - et al.
Subtyping primary insomnia: is sleep state misperception a distinct clinical entity?
Sleep. Med. Rev.
(2003) - et al.
Sleep, illness course, and concurrent symptoms in inter-episode bipolar disorder
J. Behav. Ther. Exp. psychiatry
(2010) - et al.
Sleep in remitted bipolar disorder: a naturalistic case-control study using actigraphy
J. Affect. Disord.
(2014) - et al.
Comparison of objective and subjective assessments of sleep time in subjects with bipolar disorder
J. Affect. Disord.
(2013) - et al.
Sleep functioning in relation to mood, function, and quality of life at entry to the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)
J. Affect. Disord.
(2009)