<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article  PUBLIC "-//NLM//DTD Journal Publishing DTD v3.0 20080202//EN" "http://dtd.nlm.nih.gov/publishing/3.0/journalpublishing3.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="3.0" xml:lang="en" article-type="research article"><front><journal-meta><journal-id journal-id-type="publisher-id">OJOG</journal-id><journal-title-group><journal-title>Open Journal of Obstetrics and Gynecology</journal-title></journal-title-group><issn pub-type="epub">2160-8792</issn><publisher><publisher-name>Scientific Research Publishing</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.4236/ojog.2013.31A034</article-id><article-id pub-id-type="publisher-id">OJOG-27772</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Medicine&amp;Healthcare</subject></subj-group></article-categories><title-group><article-title>
 
 
  Psychological distress and SSRI use predict variation in inflammatory cytokines during pregnancy
 
</article-title></title-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>wen</surname><given-names>Latendresse</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>R.</surname><given-names>Jeanne Ruiz</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Bob</surname><given-names>Wong</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib></contrib-group><aff id="aff2"><addr-line>College of Nursing, University of Texas-Austin, Austin, USA</addr-line></aff><aff id="aff1"><addr-line>College of Nursing, University of Utah, Salt Lake City, USA</addr-line></aff><author-notes><corresp id="cor1">* E-mail:<email>gwen.latendresse@nurs.utah.edu(WL)</email>;</corresp></author-notes><pub-date pub-type="epub"><day>04</day><month>02</month><year>2013</year></pub-date><volume>03</volume><issue>01</issue><fpage>184</fpage><lpage>191</lpage><history><date date-type="received"><day>19</day>	<month>December</month>	<year>2012</year></date><date date-type="rev-recd"><day>21</day>	<month>January</month>	<year>2013</year>	</date><date date-type="accepted"><day>29</day>	<month>January</month>	<year>2013</year></date></history><permissions><copyright-statement>&#169; Copyright  2014 by authors and Scientific Research Publishing Inc. </copyright-statement><copyright-year>2014</copyright-year><license><license-p>This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/</license-p></license></permissions><abstract><p>
 
 
   Evidence supports the premise that maternal psychological distress adversely affects pregnancy outcomes and that inflammatory markers and placentally-produced corticotrophin-releasing hormone (pCRH) are likely mediating factors. The primary aim of the study was to explore the associations between maternal psychological distress, use of selective serotonin re-uptake inhibitors, pCRH, and maternal plasma inflammatory markers during pregnancy. Measures of maternal plasma pCRH, Interleukins-1, 6, &amp; 10, C-Reactive Protein, Macrophage Migration Inhibitory Factor, and Tumor Necrosis Factor-αwere completed in 100 pregnant women. Measures of depression, anxiety, and perceived stress were completed, as well as collection of demographic/behavioral data, e.g. use of selective serotonin re-uptake inhibitors (SSRIs). Significant correlations were found at 14-20 weeks gestation between IL-6 &amp; 10, and depression, anxiety, and perceived stress. Also at 14 - 20 weeks gestation, IL10 levels were significantly lower in women with 4th quartile pCRH levels and IL1β, IL6, and IL10 were significantly lower among women who took an SSRI during pregnancy. After controlling for maternal age, BMI, pCRH level, and SSRI use, psychological distress remained to explain variation in maternal inflammatory markers. These results might suggest that future research should focus on whether depression and anxiety are effectively being treated during pregnancy, and how such a scenario might contribute to an immune system pathway to poor pregnancy outcome.  
    
 
</p></abstract><kwd-group><kwd>Pregnancy; Psychological Distress; Depression; Anxiety; Cytokines; Interleukin-10; Inflammation</kwd><kwd> CRH</kwd><kwd> SSRI</kwd></kwd-group></article-meta></front><body><sec id="s1"><title>1. INTRODUCTION</title><p>Significant evidence supports the premise that chronic psychological distress contributes to adverse pregnancy outcome, such as preterm birth [1-4]. Plausible explanations include interactions between stress physiology and the normal physiology of pregnancy and birth, in addition to individual health behaviors and genomic makeup [<xref ref-type="bibr" rid="scirp.27772-ref5">5</xref>]. These interactions frequently involve immune mediators, such as interleukins (IL) 1, 6, 10, and Tumor Necrosis Factor-alpha (TNFα), and hormonal/neurohormonal mediators, such as placental corticotrophin-releasing hormone (pCRH) [6-10]. While there are several reports of significant associations between psychological distress and inflammatory markers in pregnancy [11-13], or between psychological distress and pCRH [14-17], there has been little focus on evaluating the relationships between maternal use of SSRIs during pregnancy and inflammatory markers or pCRH levels. In a previous study [<xref ref-type="bibr" rid="scirp.27772-ref18">18</xref>] we reported that pCRH and SSRI use during pregnancy were independent predictors of preterm birth. Additionally, there are conflicting studies that implicate either depression and anxiety or use of antidepressants (e.g. selective serotonin re-uptake inhibitors—SSRIs) in association with a higher risk of preterm birth [19-21]. At least one study suggests that antidepressants and psychological distress during pregnancy convey an equal risk (20%) of preterm birth [<xref ref-type="bibr" rid="scirp.27772-ref21">21</xref>]. In light of these previous findings, the current study was conducted to address the following aims: 1) evaluate the relationship between inflammatory markers and a) the use of SSRIs during pregnancy, b) pCRH, and c) psychological distress during pregnancy, and 2) determine whether psychological distress, SSRI, or pCRH levels are predictive of inflammatory markers during pregnancy after controlling for maternal BMI and age. Using the data from the same cohort of women from a previous study, and accessing the associated plasma repository in order to conduct inflammatory marker assays, we aimed to further explore these important relationships.</p><sec id="s1_1"><title>1.1. Psychological Distress Defined</title><p>Chronic stress is a multidimensional, composite concept making measurement difficult [<xref ref-type="bibr" rid="scirp.27772-ref22">22</xref>]. Stress appraisal, personal history and outlook, lifestyle, coping style, and environmental threats (real or imagined) are only some of the contributors to the experience of stress. Psychological distress has a well-documented association with, and is generally presumed to be a common response to chronic stress [23,24]. The three most commonly identified and measured aspects of psychological distress are depression, anxiety, and perceived stress. Within the context of pregnancy, psychological distress may be a marker of an elevated risk for adverse perinatal outcome [<xref ref-type="bibr" rid="scirp.27772-ref2">2</xref>].</p></sec><sec id="s1_2"><title>1.2. Psychoneuroimmunology (PNI) Framework</title><p><xref ref-type="fig" rid="fig1">Figure 1</xref> provides a PNI framework that explains the theoretical links between psychosocial and behavioral stress, psychological distress, alterations in the neurohormonal and immune systems during pregnancy, and adverse pregnancy outcome. These links form the framework for the current study.</p></sec></sec></body><back><ref-list><title>References</title><ref id="scirp.27772-ref1"><label>1</label><mixed-citation publication-type="other" xlink:type="simple">Glynn, L.M., et al. (2008) Pattern of perceived stress and anxiety in pregnancy predicts preterm birth. Health Psychology, 27, 43-51. doi:10.1037/0278-6133.27.1.43</mixed-citation></ref><ref id="scirp.27772-ref2"><label>2</label><mixed-citation publication-type="other" xlink:type="simple">Hobel, C., Goldstein, A. and Barrett, E.S. (2008) Psychosocial stress and pregnancy outcome. Clinical Obstetrics and Gynecology, 51, 333-348.  
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