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

Abstract

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.


Share and Cite:

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.

1. INTRODUCTION

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.

References

[1] 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
[2] Hobel, C., Goldstein, A. and Barrett, E.S. (2008) Psychosocial stress and pregnancy outcome. Clinical Obstetrics and Gynecology, 51, 333-348. doi:10.1097/GRF.0b013e31816f2709
[3] Behrman, R.E. and Stith Butler, A. (2007) Preterm Birth: Causes, Consequences, and Prevention. National Academy Press, Washington DC.
[4] Karimi, K. and Arck, P.C. (2010) Natural Killer cells: Keepers of pregnancy in the turnstile of the environment. Brain, Behavior, and Immunity, 24, 339-347. doi:10.1016/j.bbi.2009.09.015
[5] Latendresse, G., The interaction between chronic stress and pregnancy: preterm birth from a biobehavioral perspective. J Midwifery Womens Health, 2009. 54(1): p. 8-17. PMID: 19114234. doi:10.1016/j.jmwh.2008.08.001
[6] Challis, J.R., et al. (2000) Endocrine and paracrine regulation of birth at term and preterm. Encodrine Reviews, 21, 514-550. doi:10.1210/er.21.5.514
[7] Norwitz, E.R., Robinson, J.N. and Challis, J.R. (1999) The control of labor. New England Journal of Medicine, 341, 660-666. doi:10.1056/NEJM199908263410906
[8] Snegovskikh, V., Park, J.S. and Norwitz, E.R. (2006) Endocrinology of parturition. Endocrinology and Metabolism Clinics of North America, 35, 173-191. doi:10.1016/j.ecl.2005.09.012
[9] Challis, J.R., et al. (2002) Prostaglandins and mechanisms of preterm birth. Reproduction, 124, 1-17. doi:10.1530/rep.0.1240001
[10] Pearce, B.D. et al. (2008) Serum macrophage migration inhibitory factor in the prediction of preterm delivery. American Journal of Obstetrics and Gynecology, 199, e1-e6.
[11] Christian, L.M., et al. (2009) Depressive symptoms are associated with elevated serum proinflammatory cytokines among pregnant women. Brain, Behavior, and Immunity, 23, 750-754. doi:10.1016/j.bbi.2009.02.012
[12] Christian, L.M., et al. (2010) Depressive symptoms predict exaggerated inflammatory responses to an in vivo immune challenge among pregnant women. Brain, Behavior, and Immunity, 24, 49-53. doi:10.1016/j.bbi.2009.05.055
[13] Wright, R.J., et al. (2010) Prenatal maternal stress and cord blood innate and adaptive cytokine responses in an inner-city cohort. American Journal of Respiratory and Critical Care Medicine, 182, 25-33. doi:10.1164/rccm.200904-0637OC
[14] Mancuso, et al. (2004) Maternal prenatal anxiety and corticotropin-releasing hormone associated with timing of delivery. Psychosomatic Medicine, 66, 762-769. doi:10.1097/01.psy.0000138284.70670.d5
[15] Latendresse, G. and Ruiz, R.J. (2010) Maternal coping style and perceived adequacy of income predict CRH levels at 14-20 weeks of gestation. Biological Research for Nursing, 20798157.
[16] Hobel, C., et al. (1999) Maternal plasma corticotropinreleasing hormone associated with stress at 20 weeks’ gestation in pregnancies ending in preterm delivery. American Journal of Obstetrics and Gynecology, 180, S257-S263. doi:10.1016/S0002-9378(99)70712-X
[17] Dunkel Schetter, C. (2011) Psychological science on pregnancy: Stress processes, biopsychosocial models, and emerging research issues. Annual Review of Psychology, 62, 531-58. doi:10.1146/annurev.psych.031809.130727
[18] Latendresse, G. and Ruiz, R.J. (2011) Maternal corticotropin-releasing hormone and the use of selective serotonin reuptake inhibitors independently predict the occurrence of preterm birth. Journal of Midwifery Womens Health, 56, 118-126. doi:10.1111/j.1542-2011.2010.00023.x
[19] Suri, R., et al. (2007) Effects of antenatal depression and antidepressant treatment on gestational age at birth and risk of preterm birth. American Journal of Psychiatry, 164, 1206-1213. doi:10.1176/appi.ajp.2007.06071172
[20] Dayan, J., et al. (2006) Prenatal depression, prenatal anxiety, and spontaneous preterm birth: A prospective cohort study among women with early and regular care. Psychosomatic Medicine, 68, 938-946. doi:10.1097/01.psy.0000244025.20549.bd
[21] Wisner, K.L., et al. (2009) Major depression and antidepressant treatment: impact on pregnancy and neonatal outcomes. American Journal of Psychiatry, 166, 557-566. doi:10.1176/appi.ajp.2008.08081170
[22] D’Anna-Hernandez, K.L., et al. (2012) Acculturation, maternal cortisol, and birth outcomes in women of Mexican descent. Psychosomatic Medicine, 74, 296-304. doi:10.1097/PSY.0b013e318244fbde
[23] Chrousos, G. (1998) Stressors, stress, and neuroendocrine integration of the adaptive response. Annual New York Academic Science, 851, 311-335. doi:10.1111/j.1749-6632.1998.tb09006.x
[24] Kudielka, B.M. and Wust, S. (2010) Human models in acute and chronic stress: Assessing determinants of individual hypothalamus-pituitary-adrenal axis activity and reactivity. Stress, 13, 1-14. doi:10.3109/10253890902874913
[25] Coussons-Read, M.E., Okun, M.L. and Nettles, C.D. (2007) Psychosocial stress increases inflammatory markers and alters cytokine production across pregnancy. Brain, Behavior, and Immunity, 21, 343-350. doi:10.1016/j.bbi.2006.08.006
[26] Kalantaridou, S.N., et al. (2010) Corticotropin-releasing hormone, stress and human reproduction: an update. Journal of Reproductive Immunology, 85, 33-39. doi:10.1016/j.jri.2010.02.005
[27] Gotsch, F., et al. (2008) The anti-inflammatory limb of the immune response in preterm labor, intra-amniotic infection/inflammation, and spontaneous parturition at term: a role for interleukin-10. Journal of Maternal Fetal and Neonatal Medicine, 21, 529-547. doi:10.1080/14767050802127349
[28] Pearce, B.D., et al. (2010) Interrelationship of cytokines, hypothalamic-pituitary-adrenal axis hormones, and psychosocial variables in the prediction of preterm birth. Gynecology and Obstetrics Investigation, 70, 40-46. doi:10.1159/000284949
[29] Entringer, S., et al. (2008) Influence of prenatal psychosocial stress on cytokine production in adult women. Developmental Psychobiology, 50, 579-587. doi:10.1002/dev.20316
[30] Picklesimer, A.H., et al. (2008) Racial differences in Creactive protein levels during normal pregnancy. American Journal of Obstetrics and Gynecology, 199, e1-e6.
[31] Founds, S.A., et al. (2008) A comparison of circulating TNF-alpha in obese and lean women with and without preeclampsia. Hypertension in Pregnancy, 27, 39-48. doi:10.1080/10641950701825838
[32] Hostetter, A., et al. (2000) Dose of selective serotonin uptake inhibitors across pregnancy: Clinical implications. Depression and Anxiety, 11, 51-57. doi:10.1002/(SICI)1520-6394(2000)11:2<51::AID-DA1>3.0.CO;2-R
[33] Patil, A.S., Kuller, J.A. and Rhee, E.H. (2011) Antidepressants in pregnancy: A review of commonly prescribed medications. Obstetrics and Gynecology Survey, 66, 777-87. doi:10.1097/OGX.0b013e31823e0cbf

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.