Prenatal mood and anxiety disorders and associated cytokine changes.

BACKGROUND: We examined whether women with prenatal mood and anxiety disorders would exhibit differential pro- and anti-inflammatory marker trajectories during the prenatal and postpartum periods compared to women without these disorders. METHODS: Approximately 179 pregnant women participated in a longitudinal study conducted in two urban areas. Blood samples for inflammatory markers were collected at six study visits. The Structured Clinical Interview for the DSM-IV (SCID) was administered to participants scoring above cutoffs on anxiety and depression. Pregnant women with SCID Axis I diagnoses of mood and/or anxiety disorders were compared to other participants on inflammatory markers. Multilevel modeling tested associations between SCID diagnoses and within-person interleukin (IL)6 and IL10 trajectories. RESULTS: Prenatal SCID diagnoses were associated with linear, quadratic and cubic change in IL6 from prenatal to postpartum timepoints. Women with a prenatal SCID diagnosis had steeper decreases and increases in IL6 during prenatal and postpartum periods. SCID diagnoses were associated with lower IL10 in mid-pregnancy to postpartum (b = -0.078, SE = 0.019; p = .015). LIMITATIONS: Future studies would benefit from a larger sample size and a larger number of participants with SCID diagnoses. Future research should also examine whether different prenatal Axis 1 diagnoses are associated with different patterns of immune response in pregnancy. CONCLUSIONS: Pregnant women with prenatal mood and anxiety disorders had greater fluctuations in IL6 across prenatal and postpartum periods and lower IL10 through pregnancy and postpartum. They may have different proinflammatory states that remain after birth without a reciprocal anti-inflammatory response.

Inflammatory and immune marker trajectories from pregnancy to one-year post-birth.

BACKGROUND: Pregnancy is an immunomodulatory state, with reported systematic changes in inflammatory and immune activity by pregnancy stage. Published data are inconsistent as to how inflammatory and immune markers change and recover across pregnancy and the postpartum period, or the sociodemographic, health and pregnancy-related factors that could affect biomarker trajectories. The purpose of this study is to describe inflammatory and immune marker trajectories from pregnancy to a year post-birth, and to test associations with sociodemographic, health and pregnancy-related variables. METHODS: A sample of 179 pregnant women were assessed three times during pregnancy (between 8 and 36 weeks gestation) and three times during the postpartum period (between 1 and 12 months). Maternal sociodemographic characteristics, health, and pregnancy factors were obtained at study entry. Blood samples from each assessment were assayed for interleukin(IL)-6, tumor necrosis factor(TNF)α, IL-8, IL-10, and interferon(IFN)γ. Multilevel modelling was used to characterize biomarker trajectories and associations with sociodemographic and health variables. RESULTS: Distinct trajectories over time emerged for each biomarker. Male pregnancies were associated with higher TNFα, IL-10, and IFNγ; higher pre-pregnancy BMI was associated with higher IL-6 and IFNγ. Nulliparity was associated with greater increases in IL-6 and TNFα. CONCLUSIONS: Patterns observed for inflammatory and immune markers from pregnancy to a year postpartum support the hypothesis that the maternal immune system changes systematically across pregnancy and through an extended postpartum period. Parity, pre-pregnancy BMI and child sex are associated with inflammatory marker patterns over time. These results contribute to our understanding of how immune system activity changes from pregnancy to the post-birth period, and the factors that could affect those changes.

Sleep hygiene behaviors among midlife women with insomnia or sleep-disordered breathing: the SWAN sleep study.

BACKGROUND: Insomnia and sleep-disordered breathing (SDB) are the most common sleep disorders among midlife women. Although promoting sleep hygiene behaviors may be a useful behavioral approach for the management of insomnia or SDB, the frequency with which women engage in these behaviors is unclear. METHODS: Participants were from the Study of Women's Health Across the Nation (SWAN) Sleep Study (N=321; age range=48-58 years). Out of the full sample, 10.3% (n=33) met Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition diagnostic criteria for insomnia, 15.3% (n=49) had clinically significant SDB (apnea-hypopnea index ≥15), and 4.7% (n=15) met criteria for both insomnia and SDB, resulting in an overall prevalence of 15.0% (n=48) for insomnia and 19.9% (n=64) for SDB. Participants provided diary-based assessments of sleep hygiene behaviors for 14-35 days. Two positive behaviors (sufficient exercise, regular morning out-of-bed time) and four negative behaviors (taking long daytime naps, caffeine consumption near bedtime, alcohol consumption near bedtime, smoking) were examined. These behaviors were compared between women with and without insomnia or SDB following adjustment for sociodemographic factors and mental and physical health indices. RESULTS: Women with insomnia engaged in significantly fewer negative sleep hygiene behaviors than women without insomnia (1.61±0.15 vs. 2.09±0.09 behaviors; p<0.01); specifically, women with insomnia were less likely to take long naps (odds ratio [OR]=0.30, 95% confidence interval [CI]: 0.12-0.74) or consume caffeine near bedtime (OR=0.44, 95% CI: 0.20-0.98). In contrast, women with SDB were less likely to be physically active than women without SDB (OR=0.52, 95% CI: 0.27-0.98), but no other differences in sleep hygiene behaviors were observed. CONCLUSIONS: These data suggest that insomnia in midlife women is not associated with poor sleep hygiene. Increasing physical activity may be a valuable recommendation for midlife women with SDB.

Disturbed sleep and inflammatory cytokines in depressed and nondepressed pregnant women: an exploratory analysis of pregnancy outcomes.

OBJECTIVE: Disturbed sleep and depression are potential risk factors for pregnancy complications. Both conditions are known to dysregulate biological pathways responsible for maintaining homeostatic balance and pregnancy health. Depression during pregnancy is associated with poor sleep. Thus, we explored whether disturbed sleep was associated with inflammatory cytokines and risk for adverse pregnancy outcomes, as well as whether depression augmented the sleep-cytokine relationship, thereby additively contributing to risk for adverse outcomes. METHODS: Interview-assessed sleep and plasma cytokine concentrations were evaluated in a cohort of depressed and nondepressed pregnant women (n = 168) at 20 and 30 weeks' gestation. Outcomes evaluated included preterm birth, birth weight, and peripartum events. RESULTS: Among depressed women, short sleep duration (<7 hours) was associated with higher interleukin (IL)-8 across time (ß = 0.506, p = .001), poor sleep efficiency (<85%) was associated with higher IL-6 (ß = 0.205, p = .006), and daytime naps were associated with higher tumor necrosis factor α (ß = 0.105, p = .024). Aspects of poor sleep were associated with having a lower weight baby (p values <.053). Among depressed women, interferon-γ increased risk for preterm birth (odds ratio = 1.175, p = .032). Trends for IL-6 and higher birth weight (ß = 105.2, p = .085), interferon-γ and lower birth weight (ß = -19.92, p < .069), and increased IL-8 and babies weighing less than 4000 grams (odds ratio = 0.72, p < .083) were observed. CONCLUSIONS: Although speculative, disturbed sleep may disrupt normal immune processes and contribute to adverse pregnancy outcomes. Exploratory analyses indicate that depression modifies these relationships.

Subjective sleep disturbance during a smoking cessation program: associations with relapse.

BACKGROUND: Sleep disturbance may affect smoking cessation efforts. We describe sleep changes across three months among women in a smoking cessation program and tested whether sleep disturbances at baseline and 1 month post-quit attempt predicted smoking status at three months. METHODS: Participants (N=322) were women in a randomized, clinical trial for smoking cessation. Sleep disturbances, as well as, insomnia, drowsiness, and sleep quality were evaluated prior to and during three months of cessation treatment. Repeated measures mixed models evaluated change in sleep over time by smoking outcome status. Logistic regression analyses determined whether sleep disturbances at baseline and 1 month post-quit were associated with smoking status at 3 months. RESULTS: Sleep disturbances were reported by more than 25% of women. Drowsiness, insomnia, and sleep quality changed over time. However, contrary to our hypotheses, none of the sleep variables at either baseline or 1 month post-quit attempt was associated with relapse (p's>.05). CONCLUSIONS: Although mild to severe drowsiness was reported by more women who relapsed than those who remained abstinent, none of the sleep disturbance symptoms predicted smoking relapse. Given high rates of sleep disturbances among women smokers, better prospective evaluations of the relationship of sleep disturbances to smoking cessation treatment outcome are needed.

Sleep variability, health-related practices, and inflammatory markers in a community dwelling sample of older adults.

OBJECTIVE: To explore relationships between wake- and sleep-related health behaviors and circulating concentrations of inflammatory markers (interleukin [IL]-6 and tumor necrosis factor [TNF]-α) in a cohort of community dwelling older adults. Low-grade chronic inflammation is an important risk factor for age-related morbidity. Health behaviors, including average aggregate measures of sleep, have been linked to increased inflammation in older adults. Variability in sleep timing may also be associated with increased inflammation. METHOD: Participants were community dwelling older adults ≥ 60 years (n = 222: 39 bereaved, 55 caregivers, 52 with insomnia, and 76 good sleepers). Mean values and intraindividual variability in sleep, as well as caffeine and alcohol use, exercise, and daytime napping, were assessed by sleep diaries. Blood samples were obtained in the morning. RESULTS: Several interactions were noted between sleep behaviors, inflammatory markers, and participant group. Greater variability in wake time and time in bed was associated with higher IL-6 among good sleepers relative to caregivers and older adults with insomnia. Good sleepers who consumed moderate amounts of alcohol had the lowest concentrations of IL-6 compared with the other three groups who consumed alcohol. Insomnia subjects, but not good sleepers, showed increased concentrations of IL-6 associated with caffeine use. Caregivers showed increased concentrations of TNF-α with alcohol use relative to good sleepers. Greater variability in bedtime, later wake times, and longer time in bed was associated with higher TNF-α regardless of group. CONCLUSIONS: Moderation and regularity in the practice of certain health behaviors, including sleep practices, were associated with lower plasma levels of inflammatory markers in older adults. Life circumstances and specific sleep disorders may modify these associations.

Changes in sleep quality, but not hormones predict time to postpartum depression recurrence.

BACKGROUND: Poor sleep quality, dysregulation of hormones and increased inflammatory cytokines are all associated with the risk for postpartum major depression (PPMD). We evaluated change over time in sleep quality and hormones during the first 17 weeks postpartum, as well as a single cytokine measure, and their association with PPMD recurrence. METHODS: Participants were pregnant women (N=56), with past histories of MDD/PPMD but not depressed in their current pregnancy. The Pittsburgh Sleep Quality Index (PSQI) and blood samples were collected 8 times during the first 17 weeks postpartum. Estradiol, prolactin and cortisol, and a single measure of IL-6 were assayed. Recurrence was determined by two consecutive 21-item Hamilton Rating Scale for Depression (HRSD) scores≥15 and clinician interview. RESULTS: In the analyses of time to PPMD recurrence, poor sleep quality, but none of the hormones, was associated with PPMD recurrence (p<.05) after controlling for medication assignment. With every one point increase in PSQI scores across time, a woman's risk for recurrence increased by approximately 25% There was no significant association between PSQI scores and IL-6 concentrations in early postpartum (χ(2)=0.98, p=.32). CONCLUSIONS: Poor sleep quality across the first 17 weeks post-delivery increases the risk for recurrent PPMD among women with a history of MDD. Changes in the hormonal milieu were not associated with recurrence. Further exploration of the degree to which poor sleep contributes to hormonal and cytokine dysregulation and how they are involved in the pathophysiology of PPMD is warranted.

Disturbed sleep is associated with increased C-reactive protein in young women.

Evidence links disturbed sleep with an exaggerated inflammatory response and increased risk of adverse health outcomes. An emerging risk factor for many adverse health outcomes is chronic, low-grade inflammation. An exaggerated inflammatory response could provide a biological link between disturbed sleep and adverse health outcomes. The relationship between sleep and chronic, low-grade inflammation has been sparsely examined in otherwise healthy, young women. We evaluated cross-sectional relationships between self-reported sleep and three inflammatory markers. Participants were community dwelling nonpregnant women (N=43, 28.2+/-5.2 years of age). Measures included the Pittsburgh Sleep Quality Index (PSQI), sleep diaries, and serum levels of IL-6, TNF-alpha and C-reactive protein. Poor sleep quality and continuity were associated with higher CRP levels after controlling for covariates. No significant relationships were observed between PSQI scores and IL-6 or TNF-alpha; sleep duration was not related to any of the inflammatory markers. Poor sleep, in young adulthood, may contribute to the chronic, low-grade inflammation associated with an increased risk for future adverse health outcomes. Future work should longitudinally evaluate how these relationships may affect development of gender-specific diseases in apparently healthy young women.

Sleep disturbances increase interleukin-6 production during pregnancy: implications for pregnancy complications.

Pregnant women experience disturbed sleep that varies throughout the gestational period. In clinical studies of nonpregnant cohorts, data link disturbed sleep with increases in inflammatory markers. Emerging evidence has also found associations between increased inflammation and medical morbidity, including various pregnancy complications. The authors have previously shown a correlation between sleep disturbances and serum cytokine levels. They extend this initial observation by evaluating the relationship between sleep during mid and late pregnancy and inflammatory cytokines in both serum and stimulated peripheral blood mononuclear cells. Subjective sleep during pregnancy, described by the Pittsburgh Sleep Quality Index and sleep diaries, and circulating and stimulated measures of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha were evaluated in 19 pregnant women. The authors found that greater sleep complaints in late pregnancy were associated with both increased circulating and stimulated IL-6 levels. Short sleep duration and poor sleep efficiency in both mid and late pregnancy were associated with higher stimulated levels of IL-6. No relationships were observed for TNF-alpha. These preliminary findings indicate that women who experience sleep disturbances as early as mid gestation are likely to have an increase in inflammation.

Psychosocial stress increases inflammatory markers and alters cytokine production across pregnancy.

Previous work has shown that psychosocial stress is related to increases in serum levels of pro-inflammatory cytokines late in pregnancy, and a growing body of research suggests that increased inflammatory activity during pregnancy, generally, may have a negative impact on outcome. The present study further addressed these issues by assessing relationships between psychosocial stress, social support and serum cytokines in early, mid, and late pregnancy, and the effects of stress and social support on the production of cytokines by stimulated lymphocytes in late pregnancy. In addition, we examined relationships between stress, support, and serum C-reactive protein (CRP) during pregnancy. Elevated stress was not only related to higher serum IL-6 late in pregnancy as in our prior work, but this relationship was also evident during early pregnancy and elevated stress was also associated with lower IL-10 in early pregnancy. No relationships between stress and cytokines were apparent during the 2nd trimester of pregnancy. Elevated stress during the 2nd trimesters and low social support during the 3rd trimester were related to increased serum levels of CRP, further suggesting that psychosocial factors can contribute increased inflammation during pregnancy. Importantly, elevated stress levels across pregnancy were predictive of elevated production of the pro-inflammatory cytokines IL-1B and IL-6 by stimulated lymphocytes in the 3rd trimester, suggesting that stress during pregnancy affects the function of immune system cells. These findings further support the notion that prenatal stress alters maternal physiology and immune function in a manner consistent with increased risk of pregnancy complications such as preeclampsia and premature labor.

Prenatal stress alters cytokine levels in a manner that may endanger human pregnancy.

OBJECTIVE: Recent data suggest that prenatal stress negatively affects pregnancy and infant outcome. Existing studies implicate dysregulation of the immune and endocrine systems in stress-related increases in premature labor and poor birth outcome, but no published studies have directly addressed the relationships among these variables during pregnancy. We sought to test the hypothesis that high levels of psychosocial stress and low levels of social support during pregnancy alter maternal cytokine profiles in a manner that contributes to poor birth outcomes. METHODS: Psychosocial stress and social support were measured in 24 women with overtly normal pregnancies once during each trimester of pregnancy. Levels of interleukin-10 (IL-10), IL-6, and tumor necrosis factor-alpha (TNF-alpha) were assessed concurrently with stress and support measurements. RESULTS: High social support was associated with low stress scores. Elevated stress scores were positively correlated with higher levels of the proinflammatory cytokines IL-6 and TNF-alpha, and with low levels of the antiinflammatory cytokine IL-10. CONCLUSIONS: These findings provide initial support for our hypothesis that stress-related neural immune interactions may contribute to pregnancy complications and poor outcome, but require further study to determine the mechanism and significance of these effects.