Sleep and chronotype during pregnancy, and the bright light treatment of perinatal depression

Background
Perinatal depression (PND) is a severe mental disorder with disruptive consequences on the health and well-being of mothers, children, and their families. Due to the induced socioeconomic burden, it also represents a major public health problem for society as a whole, and is therefore considered a priority target of health prevention strategies at a global level. There is, in fact, general consensus among experts that PND is still prevalent, underrecognized and undertreated.
While research on the pathophysiological mechanisms of PND is contributing to an increased knowledge of the multifactorial causes of this condition, and is likely to provide new biomarkers for medical use in the near future, none of these is currently available for the everyday clinical practice. Conversely, there is an urgent need of easy and universal screening instruments, as well as safe and affordable treatments that all women can have access to.
Sleep and circadian rhythm disruption are commonly experienced by women during the perinatal period, but there is limited evidence on the objective changes in sleep parameters occurring during pregnancy and how these relate to health outcomes. Moreover, the role of sleep and circadian factors in the etiology of PND and as potential targets for treatment is still underestimated and underinvestigated. As an example, the influence of different circadian preferences for sleep-wake times (chronotypes) on the development of depressive symptoms across the perinatal period has never been investigated. Likewise, the efficacy and safety of bright light therapy (BLT) for the treatment of PND with onset before and/or after delivery have never been tested.
Objectives
Manuscript 1: to perform the first systematic review and meta-analysis of polysomnographic studies during pregnancy, in order to identify possible objective markers of sleep disruption in pregnant women.
Manuscript 2: to investigate whether chronotype is a risk factor for PND and to explore the association between chronotype, maternal sociodemographic characteristics, and lifestyle habits, in relation to PND.
Manuscript 3: to conduct the first randomized controlled trial (RCT) aimed at testing the efficacy and safety of BLT for PND occurring over a 12-month observation period.
Methods
Manuscript 1: by carefully following the PRISMA guidelines, we conducted the first systematic review of polysomnographic studies during pregnancy available in the literature. In addition, we performed a meta-analysis of the data collected on two sleep variables (TST and SE). This was instead not possible for other sleep parameters, due to the large heterogeneity of the reviewed studies.
Manuscript 2: as a part of the “Life-ON” project, a multicenter, prospective, cohort study on sleep and mood changes during the perinatal period, 299 women were followed-up from the first trimester of pregnancy until 6 months postpartum. Chronotype was assessed at baseline using the MEQ, while mood was repeatedly evaluated at several timepoints with depression rating scales (i.e., EPDS, HDRS, and MADRS). The influence of time and chronotype on the different scales was estimated by constructing multilevel linear mixed regression models. A Cox proportional-hazard regression model was built to evaluate the association between chronotype and incidence of depression.
Manuscript 3: in the frame of the “Life-ON” project, a RCT was conducted in a subsample of women with an EPDS score >12 at any time point from the second trimester of pregnancy up to 6 months postpartum. Participants received either BLT (10’000 lux) or DRL (19 lux) for 6 weeks, 30 minutes in the morning, within 20 minutes after wake up, and at a distance of 30 cm from the light box. Multilevel linear models were constructed to test for the influence of time and treatment group on EPDS values and log-linear models to test for socioeconomic factors influencing PND remission.
Results
According to our systematic review, the main changes in objective sleep parameters during pregnancy consists in a reduction of sleep duration and a fragmentation of sleep continuity, with an increased number of awakenings and superficial sleep stages (N1, N2), and a simultaneous decrease of SWS, REM sleep, and SE. The meta-analysis revealed a significant reduction of TST by 26.8 min between the first and third trimester of pregnancy, as well as a decrease of SE by 4% within the same time frame.
Pregnant evening chronotypes, as compared to the other chronotypes, are more vulnerable to PND symptoms, especially in the immediate postpartum period. Although the survival analysis did not show a statistically significant influence of chronotype on the overall risk of PND, a trend towards an increased risk for PND in evening chronotypes and a reduced risk in intermediate types, as compared to morning types, was observed. Furthermore, in line with the literature, pregnant women with evening chronotype in the Life-ON study were more likely subject to health problems and negative pregnancy outcomes than the other chronotypes, and presented adverse sociodemographic characteristics and lifestyle attitudes, that are commonly associated with a higher risk for PND.
Finally, in a RCT testing 6-week morning BLT (10’000 lux) vs. DRL (19 lux) for treating PND, the active light intervention (BLT) showed a remarkable efficacy in inducing a rapid remission from PND compared to DRL. The multilevel linear model revealed a significant influence of time on EPDS score and a group-time interaction, with a greater and sustained reduction in the BLT-group across the whole follow-up period.
Conclusion
We found evidence that the subjective experience of sleep deterioration, that many women report during pregnancy, is related to objective alterations in sleep architecture, particularly during late gestation. These can only be appropriately recorded by PSG, which should be therefore considered a valuable and sometimes necessary instrument to correctly diagnose sleep disorders, also during pregnancy, by overcoming under- or overestimation bias due to subjective reports of sleep problems. Interestingly, despite several physiological factors may be involved in the subjective worsening of sleep quality across gestation, is not pregnancy per se, that causes major PSG-assessed sleep disorders in healthy, normal-weight women. Rather, it is likely the combination of predisposing factors, such as obesity, higher maternal age or hypertension, and physiological changes occurring during pregnancy, that may contribute in particular to the development of obstructive sleep apnea (OSA) in at-risk pregnant women.
Evening chronotype is associated with a time-dependent, greater severity of PND. Thus, assessing chronotype during pregnancy via the administration of an easy screening questionnaire, may help identify women who are likely to experience more severe perinatal depressive symptoms, especially in the early postpartum, and provide them with psychiatric/psychological support and treatment.
BLT can not only induce a rapid and significant remission from PND compared to DRL, but the resulting improvement in mood can be maintained over time after treatment completion. These new findings support the integration of BLT as effective and safe chronotherapeutic tool, based on solid scientific evidence, to the equipment available to clinicians for the treatment of PND, thus responding to the need for affordable, easy-to-use, and accessible therapies for patients.