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

Investigating the relationship between sleep and postpartum depression: a longitudinal study examining the relationships between subjective and objective sleep during the perinatal period and postpartum depression.

Research has suggested that a bi-directional relationship exists between sleep disruption and depression. Not only is poor sleep a commonly reported symptom in those with depression, some aspects of sleep have also been shown to predict the onset of depression. Despite sleep problems being a commonly reported occurrence throughout the perinatal period, the field of perinatal sleep research remains in its relative infancy. However, recent studies suggest that sleep disturbances during this time may increase the risk of developing postpartum depression. Currently, research in this area is limited by studies that have failed to control for depressive symptoms at baseline, relied upon subjective, often retrospective, measures of sleep, and have only measured symptoms of postpartum depression in the early postpartum period. Few studies have used polysomnography, considered the ‘gold standard’ of sleep, and no studies to date have specifically compared the relationship between subjective and objective sleep. Therefore, the major aim of this thesis was to gain a better understanding of the specific aspects of sleep that were most relevant to postpartum depression. In order to address this aim, studies were carried out to: explore the aspects of sleep most relevant to major depressive disorder; examine differences in sleep between pregnant and non-pregnant women; investigate the relationships between subjective and objective measures of sleep; explore longitudinal changes in sleep, fatigue and depression throughout the perinatal period, and finally; examine which aspects of sleep at which time-point were most relevant to the development of postpartum depression. Overall this thesis found that women experience significant changes to their sleep throughout the perinatal period. While the sleep of third trimester women is considerably poorer than that of non-pregnant women (both objectively and subjectively), the most significant changes occur in the transition between late pregnancy and the early postpartum period. Furthermore, increased amounts of sleep and reports of difficulty falling asleep during late pregnancy predicted the development of postpartum depressive symptoms. This suggests that certain aspects of sleep during late pregnancy may serve as markers for women at risk of developing postpartum depression

Sensor Technologies to Manage the Physiological Traits of Chronic Pain: A Review

Non-oncologic chronic pain is a common high-morbidity impairment worldwide and acknowledged as a condition with significant incidence on quality of life. Pain intensity is largely perceived as a subjective experience, what makes challenging its objective measurement. However, the physiological traces of pain make possible its correlation with vital signs, such as heart rate variability, skin conductance, electromyogram, etc., or health performance metrics derived from daily activity monitoring or facial expressions, which can be acquired with diverse sensor technologies and multisensory approaches. As the assessment and management of pain are essential issues for a wide range of clinical disorders and treatments, this paper reviews different sensor-based approaches applied to the objective evaluation of non-oncological chronic pain. The space of available technologies and resources aimed at pain assessment represent a diversified set of alternatives that can be exploited to address the multidimensional nature of pain.Ministerio de Economía y Competitividad (Instituto de Salud Carlos III) PI15/00306Junta de Andalucía PIN-0394-2017Unión Europea "FRAIL

Effects of dance therapy on balance, gait and neuro-psychological performances in patients with Parkinson's disease and postural instability

Postural Instability (PI) is a core feature of Parkinson’s Disease (PD) and a major cause of falls and disabilities. Impairment of executive functions has been called as an aggravating factor on motor performances. Dance therapy has been shown effective for improving gait and has been suggested as an alternative rehabilitative method. To evaluate gait performance, spatial-temporal (S-T) gait parameters and cognitive performances in a cohort of patients with PD and PI modifications in balance after a cycle of dance therapy

Factors affecting daytime function in the sleep apnoea/hypopnoea syndrome

The sleep apnoea/hypopnoea syndrome (SAHS) is characterised by repetitive upper airway obstructions during sleep, which lead to recurrent hypoxaemia and brief arousals from sleep. SAHS patients suffer from excessive daytime sleepiness (EDS), cognitive impairments and decreased psychological well -being. Previous studies have examined relationships between the nocturnal events of SAHS and a limited number of daytime function measures, frequently in small, non -consecutive patient samples. Relationships found have been either weak or non -significant. This thesis examines the relationships between a wide range of nocturnal sleep and breathing variables and daytime function. Additionally, this thesis examines the use of subjective and objective measures of daytime sleepiness, to determine which tests provide the most useful information for SAHS patients.A pilot study found that neither the 103 patients' nor their partners' Epworth rating of sleepiness were strong predictors of SAHS severity. In 150 patients with a wide range of SAHS severity, relationships between nocturnal events and daytime function were examined using newer definitions of arousal and measures of sleep continuity. A broad battery of daytime tests were used including the maintenance of wakefulness test (MWT) and the short form (SF) -36. Unlike previous studies, all correlations were controlled for age and awake oxygen saturation, known to influence the variables measured. The current study also examined these correlations in an unselected patient sample with a range of disease severity. The study found a lack of strong relationships between conventional nocturnal sleep and breathing variables and daytime function. Few baseline variables significantly predicted CPAP use.Daytime function measures were compared within the 150 patients. The multiple sleep latency test (MSLT) and the MWT displayed a moderate, discordant relationship. Measures of cognitive function, psychological well -being and subjective sleepiness ii better related to the MWT than MSLT, suggesting that the MWT may be a more useful tool in assessing functional impairment in sleep apnoea.A randomised cross -over study, on 12 SANS patients, compared daytime sleepiness measured following a night's sleep at home (as performed in this thesis) versus a night in the sleep centre (standard protocol). Preliminary results indicated that daytime sleepiness, as measured by the MSLT and MWT, was not significantly different between the two study limbs. This suggests that the non -standard method of conducting the MSLT and MWT in this thesis does not explain the lack of correlational relationships between nocturnal measures and daytime sleepiness.The studies presented in this thesis demonstrate a lack of identified factors affecting daytime function in a group of unselected SANS patients. This may be due to inter - individual patient variability. Also, more sophisticated nocturnal SANS measures should be examined, as should more `real -life' daytime assessments, such as ambulatory EEG recorded during a patient's normal daily routine

Clinical outcome measures in dementia with Lewy bodies trials: critique and recommendations

The selection of appropriate outcome measures is fundamental to the design of any successful clinical trial. Although dementia with Lewy bodies (DLB) is one of the most common neurodegenerative conditions, assessment of therapeutic benefit in clinical trials often relies on tools developed for other conditions, such as Alzheimer's or Parkinson's disease. These may not be sufficiently valid or sensitive to treatment changes in DLB, decreasing their utility. In this review, we discuss the limitations and strengths of selected available tools used to measure DLB-associated outcomes in clinical trials and highlight the potential roles for more specific objective measures. We emphasize that the existing outcome measures require validation in the DLB population and that DLB-specific outcomes need to be developed. Finally, we highlight how the selection of outcome measures may vary between symptomatic and disease-modifying therapy trials

Clinical outcome measures in dementia with Lewy bodies trials: critique and recommendations.

The selection of appropriate outcome measures is fundamental to the design of any successful clinical trial. Although dementia with Lewy bodies (DLB) is one of the most common neurodegenerative conditions, assessment of therapeutic benefit in clinical trials often relies on tools developed for other conditions, such as Alzheimer's or Parkinson's disease. These may not be sufficiently valid or sensitive to treatment changes in DLB, decreasing their utility. In this review, we discuss the limitations and strengths of selected available tools used to measure DLB-associated outcomes in clinical trials and highlight the potential roles for more specific objective measures. We emphasize that the existing outcome measures require validation in the DLB population and that DLB-specific outcomes need to be developed. Finally, we highlight how the selection of outcome measures may vary between symptomatic and disease-modifying therapy trials