The association between insomnia-related sleep disruptions and cognitive dysfunction during the inter-episode phase of bipolar disorder

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Abstract

Sleep disturbance and cognitive dysfunction are two domains of impairment during inter-episode bipolar disorder. Despite evidence demonstrating the importance of sleep for cognition in healthy and sleep-disordered samples, this link has been minimally examined in bipolar disorder. The present study tested the association between insomnia-related sleep disruptions and cognitive dysfunction during inter-episode bipolar disorder. Forty-seven participants with bipolar disorder and a comorbid insomnia diagnosis (BD-Insomnia) and 19 participants with bipolar disorder without sleep disturbance in the last six months (BD-Control) participated in the study. Two domains of cognition were assessed: working memory and verbal learning. Insomnia-related sleep disruptions were assessed both categorically (i.e., insomnia diagnosis) and dimensionally (i.e., total wake time, total sleep time, total wake time variability, and total sleep time variability). Hierarchical linear regressions, adjusting for participant age, demonstrated that insomnia diagnosis did not have an independent or interactive effect on cognition. However, regardless of insomnia diagnosis, greater total sleep time variability predicted poorer working memory and verbal learning performance. Further, following sleep treatment, a reduction in total wake time predicted improved working memory performance and a reduction in total sleep time variability predicted improved verbal learning performance. These findings raise the possibility that sleep disturbance may contribute to cognitive dysfunction in bipolar disorder and highlight the importance of treating sleep disturbance in 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.

Section snippets

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)

  • K.A. Kaplan et al.

    Hypersomnia in inter-episode bipolar disorder: does it have prognostic significance?

    J. Affect. Disord.

    (2011)
  • A.I. Luik et al.

    Associations of the 24-h activity rhythm and sleep with cognition: a population-based study of middle-aged and elderly persons

    Sleep. Med.

    (2015)
  • A. Millar et al.

    The sleep of remitted bipolar outpatients: a controlled naturalistic study using actigraphy

    J. Affect. Disord.

    (2004)
  • T.H. Ng et al.

    Sleep–wake disturbance in interepisode bipolar disorder and high-risk individuals: a systematic review and meta-analysis

    Sleep. Med. Rev.

    (2015)
  • J.C. Robb et al.

    Quality of life and lifestyle disruption in euthymic bipolar disorder

    J. Psychiatric Res.

    (1997)
  • L.J. Robinson et al.

    A meta-analysis of cognitive deficits in euthymic patients with bipolar disorder

    J. Affect. Disord.

    (2006)
  • M. Russo et al.

    The relationship between sleep quality and neurocognition in bipolar disorder

    J. Affect. Disord.

    (2015)
  • J. Volkert et al.

    Evidence for cognitive subgroups in bipolar disorder and the influence of subclinical depression and sleep disturbances

    Eur. Neuropsychopharmacol.

    (2015)
  • P. Alhola et al.

    Sleep deprivation: impact on cognitive performance

    Neuropsychiatric Dis. Treat.

    (2007)
  • American Academy of Sleep Medicine

    The International Classification of Sleep Disorders: Diagnostic and Coding Manual, American Academy of Sleep Medicine

    (2005)
  • American Psychiatric Association

    Diagnostic and Statistical Manual-text Revision (DSM-IV-TRim, 2000)

    (2000)
  • American Psychiatric Association

    Diagnostic and Statistical Manual of Mental Disorders (DSM-5®)

    (2013)
  • D.P. Ausubel

    The Psychology of Meaningful Verbal learning

    (1963)
  • A. Baddeley

    Working memory

    Science

    (1992)
  • T. Blackwell et al.

    Poor sleep is associated with impaired cognitive function in older women: the study of osteoporotic fractures

    Journals Gerontology Ser. A Biol. Sci. Med. Sci.

    (2006)
  • T. Blackwell et al.

    Associations of objectively and subjectively measured sleep quality with subsequent cognitive decline in older community-dwelling men: the MrOS sleep study

    Sleep

    (2014)
  • D.L. Bliwise et al.

    Depression as a confounding variable in the estimation of habitual sleep time

    J. Clin. Psychol.

    (1993)
  • D.J. Buysse et al.

    Recommendations for a standard research assessment of insomnia

    Sleep.

    (2006)
  • M.W. Chee et al.

    Functional imaging of working memory after 24 hr of total sleep deprivation

    J. Neurosci.

    (2004)
  • J.D. Cohen et al.

    Temporal dynamics of brain activation during a working memory task

    Nature

    (1997)
  • D.-J. Dijk et al.

    Circadian and sleep/wake dependent aspects of subjective alertness and cognitive performance

    J. sleep Res.

    (1992)
  • S. Drummond et al.

    Neural correlates of working memory performance in primary insomnia

    Sleep

    (2013)
  • S.P. Drummond et al.

    Altered brain response to verbal learning following sleep deprivation

    Nature

    (2000)
  • J. Edinger et al.

    Reliability and validity of the duke structured interview for sleep disorders for insomnia screening, sleep

    Am. Acad. Sleep Med.

    (2009)
  • J.D. Edinger et al.

    Derivation of research diagnostic criteria for insomnia: report of an american Academy of sleep medicine work group

    Sleep

    (2004)
  • J. Fernandez-Mendoza et al.

    Insomnia with objective short sleep duration is associated with deficits in neuropsychological performance: a general population study

    Sleep

    (2010)
  • J.E. Ferrie et al.

    Change in sleep duration and cognitive function: findings from the Whitehall II Study

    Sleep

    (2011)
  • M.B. First et al.

    Structured Clinical Interview for DSM-IV axis I Disorders

    (1995)
  • Cited by (0)

    View full text