Depressive symptoms predict exaggerated inflammatory responses to an

Department of Psychology, The Ohio State University, Columbus, Ohio, USA
Brain Behavior and Immunity (Impact Factor: 5.89). 07/2013; 24(1):49-53. DOI: 10.1016/j.bbi.2009.05.055


ObjectiveStress and depressive symptoms predict exaggerated inflammatory responses to a biological challenge in nonpregnant humans and animals. The extent to which these findings generalize to pregnancy is unknown because the immune system exhibits substantial changes to support pregnancy. Notably, inflammatory responses to infectious agents play a causal role in the development of gestational hypertension as well as risk for preterm birth. Thus, depressive symptoms may increase susceptibility to these outcomes via sensitization of inflammatory processes. The current study was designed to test the hypothesis that depressive symptoms would predict an exaggerated proinflammatory response to an in vivo antigen challenge, influenza virus vaccination, among pregnant women.MethodTwenty-two pregnant women completed two study visits: baseline and 1 week after receiving influenza virus vaccination. Depressive symptoms were measured with the Center for Epidemiologic Studies Depression Scale (CES-D) at baseline. Serum levels of macrophage migration inhibitory factor (MIF) were determined using a high sensitivity immunoassay at both study visits.OutcomesAnalyses demonstrated that, as compared to those in the lowest tertile of CES-D scores, those in the highest tertile exhibited significantly higher levels of MIF 1 week after influenza virus vaccination (p = .035).ConclusionsDepressive symptoms predicted exaggerated MIF production following influenza virus vaccination during pregnancy. These data support the hypothesis that depressive symptoms are associated with sensitization of the inflammatory response during pregnancy. Thus, women with greater depressive symptoms may be more vulnerable to negative sequelae of infectious illness during pregnancy.

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Available from: Lisa M Christian
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    • "For instance, clinical studies showed that a recruited population of pregnant women (n=60) between 20 and 32 weeks of gestation with perceived stress and depressive symptomology exhibited high levels of the serum inflammatory markers IL-6 and TNF-α (p >.05). These findings led the authors to suggest that cytokine-mediated inflammatory pathways are highly associated with depressive disorders that contribute to negative perinatal outcomes for the baby and the mother [126]. Similarly, in a large scale study (n=145) pregnant women with moodrelated symptomology and a history of trauma, assessed at both 18 and 32 weeks of gestation, showed increased serum levels of IL-6 (p < .001) "
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    ABSTRACT: Abnormal function of the hypothalamic–pituitary–adrenal (HPA) axis along with the sympathetic-adrenalmedullary (SAM) axis represents the hallmark pathological findings in non-pregnant and pregnant women exhibiting major depressive disorder (MDD). Perinatal depression is highly prevalent, with an estimated prevalence exceeding 10% in most high-income countries. Pregnant women experience more stressful life events than non-pregnant women. Pregnant women with MDD show higher baseline levels of cortisol, increased levels of proinflammatory cytokines, and higher levels of hypothalamic-pituitary peptide hormones, catecholamines, and low dehydroepiandrosterone (DHEA) levels in plasma compared to those without MDD. During pregnancy the innate immune system and placental factors play crucial roles in the development of the conceptus to its full term. These factors when altered may generate a persistent dysfunction of the HPA axis that could lead to an overt transfer of cortisol and toxicity to the fetus at the expense of reduced activity of placental 11β-hydroxysteroid dehydrogenase Type 2 (11β-HSD-2). Epigenetic modifications (DNA methylation) of gene enhancers of the glucocorticoid receptor (GR) in addition to the corticotrophin-releasing hormone (CRH) and arginine-vasopressin (AVP) among other brain and placental molecules, may significantly contribute to the expression of depression during pregnancy. Pregnant women exhibiting affective disorders have a higher risk of generating preterm babies with high rates of morbidity and mortality and negative outcomes in child development compared to pregnant women without these disorders. Affective disorders in pregnant women should be taken seriously, and therapies focused in reducing or at most preventing the deleterious effects induced by stressors should be implemented to promote the welfare of both mother and baby. The goal of this paper is to describe the modulatory role of distinct paracrine and endocrine mediators including epigenetics of hormone receptors that drive the abnormal activity of the HPA axis in perinatal depression.
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    • "of response have been reported in patients with stable vs. unstable forms of coronary heart disease [17]. Exaggerated inflammatory responses to influenza vaccination have also been associated with greater depressive symptoms in older adults [13], and among pregnant women [18]. These studies underscore the potential value of influenza vaccination as a mild, controlled stimulus for investigating individual differences in inflammatory responses in vivo. "
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    ABSTRACT: C-reactive protein (CRP) is increasingly measured as a marker of systemic inflammation that predicts elevated risk for cardiovascular disease. Influenza vaccination is a mild pro-inflammatory stimulus, and the CRP response to vaccination may provide additional information on individual differences in inflammatory response and risk for disease. To document the pattern of CRP response to influenza vaccination among a large sample of older women in the Philippines. The Philippines exemplifies current global trends toward increasing rates of overweight/obesity, but also maintains relatively high rates of infectious disease. The secondary aim of the study is to investigate the impact of infectious symptoms on the pattern of response to vaccination. A community-based sample of 934 women (mean age=55.4 years) received the influenza vaccine. CRP was assessed at baseline and 72h post-vaccination. Descriptive, non-parametric, and parametric analyses were implemented to assess the magnitude of CRP response, and to investigate whether responses were associated with baseline CRP or the presence of infectious symptoms prior to vaccination. Influenza vaccination resulted in a statistically significant CRP response of 0.35mg/L (p<0.001), representing a 30.2% increase from baseline. For individuals with symptoms of infectious disease at baseline, the CRP response was smaller (12.9%) and not statistically significant (p=0.77). Lower CRP at baseline was associated with larger CRP response to vaccination in the entire sample, and among participants without recent symptoms of infection. Influenza vaccination produces a mild CRP response in the Philippines. This study extends prior research in US and European populations validating influenza vaccination as an in vivo model for investigating the dynamics of inflammation, but also raises potential complications in settings where rates of infectious disease are elevated. Copyright © 2015. Published by Elsevier Ltd.
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    • "Growing evidence suggests that psychological stress can lead to alterations in MIF levels, via alterations in HPA axis functioning (Calandra et al., 1995; Edwards et al., 2010). MIF elevations are observed in response to psychological stressors (Edwards et al., 2010; Katsuura et al., 2010) and circulating MIF levels have been associated with depressive and anxiety symptoms in a number of human (Christian et al., 2010; Edwards et al., 2010; Musil et al., 2011) and animal (Conboy et al., 2011) studies. It is currently unclear whether extreme childhood stress in the form of maltreatment may be associated with alterations in MIF levels. "
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    ABSTRACT: The study examined Hypothalamus-Pituitary-Adrenal (HPA) axis and inflammatory signaling in 206 youth with histories of prenatal drug exposure and self-reported histories of maltreatment. Youth with histories of severe neglect showed elevated levels of cortisol, the end product of the HPA axis, in comparison to youth with lower or minimal levels of neglect. Histories of severe neglect also were associated with increased levels of Macrophage Migration Inhibitory Factor (MIF), a cytokine known to be intricately involved in HPA axis regulation. Salivary MIF levels also were positively associated with youth age and prenatal drug exposure. These MIF and cortisol alterations may signal pathophysiological disruptions in the neuro-endocrine and immune systems, which may lead to trajectories of increased disease risk among vulnerable youth. Our findings also provide preliminary support for the validity and reliability of a noninvasive salivary assessment of MIF. © 2014 Wiley Periodicals, Inc. Dev Psychobiol.
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