Research paperMania triggered by sleep loss and risk of postpartum psychosis in women with bipolar disorder
Introduction
Women with bipolar disorder are at increased risk of affective psychoses (i.e. including mania, mixed episodes and psychotic depression) in the postpartum period (Jones et al., 2014). These episodes have traditionally been labelled as ‘postpartum psychosis’ (PP), with the majority of episodes having a sudden onset, typically within the first two postpartum weeks (Brockington et al., 1981; Heron et al., 2007). In the general population, PP affects approximately 1 in 1000 parous women (Kendell et al., 1987). In contrast, 20–30% of parous women with a history of bipolar disorder have experienced an episode of PP (Di Florio et al., 2013, Jones and Craddock, 2001, Wesseloo et al., 2016). This, combined with other evidence (reviewed in Jones et al., 2010), suggests that PP may be best conceptualised as a bipolar diathesis combined with a vulnerability to a puerperal (i.e. childbirth-related) trigger.
Research to date has primarily focused on how childbirth might trigger episodes of bipolar illness. Proposed triggers include changes in medication, the psychosocial adaption to parenthood, and obstetric complications, in addition to biological factors such as the dramatic hormonal changes that occur following delivery. To date, the most promising factors implicated in the aetiology of PP include primiparity, dysregulation of immune system function, and genetic factors (see Jones et al., 2014, for a recent review).
However, a plausible but understudied candidate for triggering PP is sleep disruption, which has been associated with the onset of mania (Wehr, 1991) and, of course, is characteristic of the perinatal period (Beebe and Lee, 2007). Sleep loss is a commonly reported antecedent of manic episodes (Jackson et al., 2003), a finding corroborated in clinical case-studies, longitudinal studies of sleep and mood within individuals with BD, and experimentally-induced sleep deprivation studies (Bauer et al., 2006, Leibenluft et al., 1996, Wehr, 1991, Wehr, 1989, Wehr et al., 1987, Wehr et al., 1982). This, in combination with findings that sleep deprivation can be a dramatic but short-term treatment for depression (Benedetti, 2012, Benedetti et al., 2001), has led to the hypothesis that acute sleep loss has mania-inducing effects (Wehr, 1991, Wehr et al., 1987, Wu and Bunney, 1990). Examination of the biological mechanisms that may underlie this effect is ongoing, although recent theories propose that sleep loss exerts an antidepressant effect by resetting processes that are a result of abnormal clock genes (Bunney and Bunney, 2013).
To date, few studies have examined the association between perinatal sleep loss and PP (Lewis et al., 2016). A retrospective study of parous women found that those who developed PP had significantly longer labours and were more likely to give birth during the night (Sharma et al., 2004), suggesting that women with PP experienced greater sleep disruption in the perinatal period. Furthermore, a case study of 3 women with a history of PP found that they became manic or hypomanic following experimentally-induced sleep deprivation (Strouse et al., 1992). Conversely, one of the few prospective studies on PP and perinatal sleep comparing the sleep of pregnant women with a history of BD or PP (i.e. a group at high risk of PP) to pregnant healthy controls found no significant differences in sleep/wake patterns during pregnancy between these groups (Bilszta et al., 2010). However, due to insufficient sample size, the authors were unable to compare the sleep of women who relapsed following childbirth to those who remained well. Thus it remains unclear whether women who develop PP experience greater sleep disturbance prior to episode onset. However, an alternative explanation is that women who develop PP are more sensitive than average to the sleep disturbances that typify the perinatal period. This hypothesis is plausible for two reasons. First, research examining responses to sleep deprivation finds that there is considerable variation within healthy populations, with some individuals showing more pronounced neurobehavioural sequelae than others (Rupp et al., 2012) and emerging evidence suggests that this might be moderated by genetic factors (Groeger et al., 2008, Kuna et al., 2012). Second, although it is thought that individuals with psychiatric disorders are more vulnerable to the negative effects of sleep disturbance than healthy populations, there is evidence of variation in response to sleep deprivation within the BD population. For example, Benedetti and colleagues have found that an antidepressant response to sleep deprivation in individuals with BD is associated with genetic factors (Benedetti et al., 2012, Benedetti and Smeraldi, 2009). This variation within the BD population in how individuals respond to sleep loss may extend to women in the perinatal period, with some women with BD being more sensitive to perinatal sleep disturbance and therefore potentially more susceptible to PP.
In light of the above literature, and given that episodes of PP typically have a manic presentation (Brockington et al., 1981), we hypothesised that women with BD who report episodes of mania being triggered by sleep loss would be more likely to experience PP than those who do not report sleep loss as a trigger for manic episodes. This paper explores this hypothesis in parous women (i.e. women who have given birth) who were recruited to the Bipolar Disorder Research Network (BDRN, bdrn.org).
Section snippets
Recruitment
Data were analysed from an ongoing large clinical and molecular genetic research programme of mood disorders, the Bipolar Disorder Research Network (BDRN). Participants are recruited systematically and non-systematically from a variety of settings including UK community mental health teams, media and patient support organizations (such as Bipolar UK). Recruitment methods and further information about BDRN has been reported elsewhere (Di Florio et al., 2013). The research programme has UK
Sample characteristics and perinatal episodes
Within the BDRN cohort, 870 women met the inclusion criteria for this study. Within the sample, 23.5% of women had experienced a lifetime episode of postpartum psychosis (n = 204) and a further 21.2% (n = 184), while not experiencing PP, had experienced non-psychotic depression within 6 weeks of delivery. The remaining women who did not meet criteria for PP or PD within 6 weeks of delivery, had experienced (i) no perinatal episodes despite giving birth (n = 207, 23.8%) or (ii) while not meeting
Discussion
We examined rates of lifetime postpartum mood episodes in parous women with BD-I according to self-report of sleep loss triggering episodes of mania or depression. Women who reported that sleep loss had triggered episodes of mania were more than twice as likely to have experienced PP. This effect remained significant when controlling for potential confounders.
The association between sleep loss and postpartum episodes was specific to i) a vulnerability to sleep disturbance triggering mania
Conclusions
In summary, our results suggest that individual differences in vulnerability to mood dysregulation following sleep loss in bipolar disorder may be a promising marker for identifying women at heightened risk of PP.
Further study in prospective samples is required in order to confirm these findings, which may have important implications for understanding the aetiology of PP and of mood disorders more generally.
Funding sources
KJSL is funded by a Medical Research Council Studentship [grant number MR/N501918/1]. The current project was supported by grants from the Wellcome Trust [grant number 078901] and the Stanley Medical Research Institute [grant number 6045240-5500000100). The funding sources had no role in the study design, in the collection, analysis, and interpretation of data, in the writing of the report and in the decision to submit the article for publication.
Acknowledgements
The authors would like to thank the funders and all members of the Bipolar Disorder Research Network (www.bdrn.org). In particular, we wish to express our continued gratitude to all of the women who kindly gave their time to help with this research.
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