Psychological distress and SSRI use predict variation in inflammatory cytokines during pregnancy


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, & 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 & 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.

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Latendresse, G. , Ruiz, R. and Wong, B. (2013) Psychological distress and SSRI use predict variation in inflammatory cytokines during pregnancy. Open Journal of Obstetrics and Gynecology, 3, 184-191. doi: 10.4236/ojog.2013.31A034.


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 [5]. 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 [18] 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 [21]. 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.

1.1. Psychological Distress Defined

Chronic stress is a multidimensional, composite concept making measurement difficult [22]. 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 [2].

1.2. Psychoneuroimmunology (PNI) Framework

Figure 1 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.

Conflicts of Interest

The authors declare no conflicts of interest.


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