Restless pillow, ruffled mind: sleep and affect coupling in interepisode bipolar disorder.

Bipolar disorder is a severe psychiatric illness that affects approximately 2% to 4% of the U.S. population (Merikangas et al., 2007) and is ranked among the top 10 leading causes of disability worldwide (World Health Organization, 2001). Despite advances in the treatment of bipolar disorder recurrence rates remain high (Gitlin, Swendsen, Heller, & Hammen, 1995), and a significant proportion of bipolar patients continue to be symptomatic and functionally impaired between episodes of illness (Altshuler et al., 2006; Joffe, MacQueen, Marriott, & Young, 2004; Vieta, Sanchez-Moreno, Lahuerta, & Zaragoza, 2008). The persistence of interepisode symptoms and impairment are of great concern because these reduce patients’ quality of life and interfere with recovery (Gitlin, Mintz, Sokolski, Hammen, & Altshuler, 2011; Judd et al., 2008). To date, the interepisode period has received minimal research attention. By shifting the focus of study to this period it may be possible to identify the factors that sustain impairment outside of acute episodes and maintain vulnerability to triggers of relapse. This study focuses on two such factors: sleep and affective functioning. Disturbed sleep is a core feature of clinical episodes in bipolar disorder (DSM–IV–TR; American Psychiatric Association, 2000). Several short-term prospective studies document the persistence of sleep difficulties between episodes of bipolar disorder. Interepisode bipolar participants report longer sleep onset latencies on daily sleep diaries relative to control participants (Harvey, Schmidt, Scarna, Semler, & Goodwin, 2005; Millar, Espie, & Scott, 2004) and exhibit more variability in actigraphy-measured sleep and wake durations relative to controls (Millar et al., 2004). Another study employing actigraphy found no significant group differences in sleep onset latency, sleep duration, or wake duration. Instead, this study found a more fragmented sleep/wake rhythm and less day-to-day stability among interepisode bipolar participants relative to controls (Jones, Hare, & Evershed, 2005). In a related line of research, participants assessed to be at risk for bipolar spectrum disorders based on scores on a hypomanic temperament scale (Meyer & Maier, 2006) and those diagnosed with bipolar spectrum disorders (Shen, Alloy, Abramson, & Sylvia, 2008) exhibited less regularity in social rhythms, or daily routines that help entrain natural circadian rhythms and the sleep-wake cycle. Reduced social rhythm regularity, in turn, predicted faster relapse among bipolar spectrum participants (Shen et al., 2008). These findings are consistent with social zeitgeber theory (Ehlers, Frank, & Kupfer, 1988; Frank, Swartz, & Kupfer, 2000), which posits that individuals with bipolar disorder have a biological vulnerability in the internal clock that regulates circadian rhythms and the sleep-wake cycle. Disruptions in social rhythms are thought to trigger this vulnerability, leading to disturbances in sleep and, ultimately, episode relapse (Frank et al., 2000; Grandin, Alloy, & Abramson, 2006). Taken together, the accruing evidence suggests that the sleep and social rhythms of bipolar participants, or those at risk for bipolar disorder, are substantially disturbed. Furthermore, the evidence suggests that disturbances in sleep and social rhythms persist outside of acute mood episodes and may play a causal role in the onset of new episodes. However, there is no agreement on the precise aspects of sleep affected. For example, we do not yet know whether subjective, objective, or both types of sleep are disturbed, nor the sleep parameters that are most disturbed, during interepisode periods of bipolar disorder. More comprehensive assessments of interepisode sleep in bipolar samples are needed to address these gaps in knowledge. A significant disturbance in mood is a defining feature of depressive, manic, hypomanic, and mixed episodes in bipolar disorder (DSM–IV–TR; American Psychiatric Association, 2000). Affective disturbances also persist between episodes of bipolar disorder. Studies using ecological momentary assessment methods conducted over the course of one to four weeks document higher levels of negative affect (Havermans, Nicolson, Berkhof, & deVries, 2010; Lovejoy & Steuerwald, 1995, but see Knowles et al., 2007 for nonreplication) and more variability in negative affect (Hofmann & Meyer, 2006; Knowles et al., 2007; Lovejoy & Steuerwald, 1995) among subsyndromal bipolar samples relative to controls. Findings with regard to positive affect, however, are less clear. Increased variability in positive affect has been consistently found among subsyndromal bipolar samples relative to controls (Hofmann & Meyer, 2006; Knowles et al., 2007; Lovejoy & Steuerwald, 1995), but support for differences from controls in mean levels of positive affect is inconsistent (Havermans et al., 2010; Hofmann & Meyer, 2006, but see Knowles et al., 2007 and Lovejoy & Steuerwald, 1995 for nonreplications). Overall, the evidence suggests that affective functioning is substantially disturbed between episodes of bipolar disorder, with more consistent findings for dysregulation in negative than positive affect. Disturbances in sleep and affect may be linked and, possibly, mutually maintaining (Harvey, 2008; Wehr, 1990). Indeed, sleep disturbance is a key predictor of mood symptoms. It is one of the most commonly reported prodromes of mania and depression (Jackson, Cavanagh, & Scott, 2003). In prospective studies with bipolar patients, sleep loss has been correlated with daily manic symptoms (Barbini, Bertelli, Colombo, Smeraldi, 1996) and with depressive symptoms at a 6-month follow-up (Perlman, Johnson, & Mellman, 2006). Self-reported changes in sleep duration have also been prospectively linked to self-reported changes in mood (measured using a single scale ranging from depressed to manic) in bipolar participants (Bauer et al., 2006). Thus, studies suggest that a disturbance in sleep can adversely impact mood. Conversely, a happy mood induced before bedtime has been associated with sleep difficulties among interepisode bipolar participants relative to controls (Talbot, Hairston, Eidelman, Gruber, & Harvey, 2009). To summarize, disturbances in sleep and mood may be bidirectionally related in bipolar disorder (Harvey, 2008; Wehr, 1990). Taken together, despite the strength of the existing findings, several issues remain unresolved. Few studies have assessed interepisode sleep comprehensively, using the entire set of the “gold standard” sleep parameters collected by both subjective and objective measures, as is recommended by established guidelines (Buysse, Ancoli-Israel, Edinger, Lichstein, & Morin, 2006), and no study to date has done so for durations longer than one week. Given substantial night-to-night variability in sleep, particularly among sleep disturbed samples, three to five weeks of daily sleep monitoring are necessary to achieve stable, representative, and reproducible estimates for key sleep parameters (Wolgemuth, Edinger, Fins, & Sullivan, 1999). Relatively short periods of observation also limit our knowledge of interepisode affect, potentially accounting for inconsistent findings with regard to positive affect. Finally, while disturbances in sleep (e.g., Barbini et al., 1996; Perlman et al., 2006) and affect (e.g., Henry et al., 2008) appear to be critical processes in maintaining pathology in bipolar disorder, their roles have been examined largely independently. Preliminary findings suggest that a laboratory-induced mood can adversely impact sleep in interepisode bipolar participants (Talbot et al., 2009). However, only one study has examined the relationship between naturally occurring affect and sleep in interepisode bipolar participants; the findings supported a bidirectional relationship between negative affect and wake time in bipolar relative to control participants (Talbot et al., in press). However, this study focused on a single sleep parameter (self-reported wake time) and was limited to one week of observation. To further clarify this important domain, the aim of the present study was to prospectively examine sleep, affect, and their potential relationship, or coupling, in interepisode bipolar disorder. Our study is the first to test this relationship by employing the most advanced methodology to date. We assessed distinct aspects of sleep using all standard sleep parameters measured via diary and actigraphy (Buysse et al., 2006). We measured both positive and negative affect. Moreover, we used daily sampling collected over the course of eight weeks. The study was designed to test three hypotheses. First, based on previous findings of pervasive sleep problems in bipolar patients during nonacute periods of illness (e.g., Harvey et al., 2005), we predicted that the bipolar group would exhibit greater sleep disturbance than the control group. Second, based on previous findings documenting pervasive affective disturbance during nonacute periods of illness (e.g., Hofmann & Meyer, 2006; Lovejoy & Steuerwald, 1995) we predicted that the bipolar group would exhibit greater affective disturbance than controls. Finally, based on previous findings suggesting sleep and affect may be closely interlinked during nonacute periods of bipolar disorder (e.g., Talbot et al., in press), we predicted greater sleep-affect coupling in the bipolar group relative to controls.