Psychiatric Symptoms and Proinflammatory Cytokines in Pregnancy

Departments of Psychiatry, University of Rochester Medical Center, 300 Crittenden Blvd, Rochester, NY 14642-8409, USA.
Psychosomatic Medicine (Impact Factor: 3.47). 09/2011; 73(8):656-63. DOI: 10.1097/PSY.0b013e31822fc277
Source: PubMed


Clinical studies suggest that psychiatric symptoms, particularly depression, anxiety, and trauma, may be associated with inflammation, as indexed by proinflammatory cytokines. Such a link may be especially significant in pregnancy and may shed additional light on the etiology of perinatal mood disorders.
We prospectively observed 145 women selected from a community obstetric clinic serving a primarily low-income, high-psychosocial risk population. Women without evidence of medical high-risk pregnancies were screened (including psychiatric and trauma histories) and then assessed in detail (e.g., mood symptoms) at approximately 18 and 32 weeks' gestation. Blood was drawn to measure key proinflammatory markers, interleukin 6 and tumor necrosis factor α (TNF-α). Data on pregnancy and obstetric outcome were derived from medical records.
There was considerable stability of cytokine levels within individuals and a significant mean increase across pregnancy observed for interleukin 6 (p < .001) and TNF-α (p < .001). History of trauma was associated with significantly elevated TNF-α levels (F(1,135) = 4.43, p < .05), controlling for psychosocial and obstetric covariates. In contrast, elevated measures of depression and anxiety were unrelated to proinflammatory cytokines (p > .1). Exploratory analyses indicated that neither psychiatric symptoms nor proinflammatory cytokines predicted birth weight, gestational age, or obstetric complications.
These findings suggest that antecedent trauma may be associated with persistently elevated TNF-α levels during pregnancy. The evidence that a generalized proinflammatory state was associated with symptoms of depression or anxiety in pregnant women was not found.

Download full-text


Available from: Thomas G O'Connor
  • Source
    • "In contrast high levels of proinflammatory cytokines were not associated with elevated measures of depression and anxiety symptoms (p > 0.1). These findings suggested that trauma history could be linked with persistent increases in TNF-α during pregnancy, but not with depressive symptomatology and/or anxiety [2]. "
    [Show abstract] [Hide abstract]
    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.
    Full-text · Article · May 2015 · Post Communist Economies
  • Source
    • "Other data suggest that sleep disturbance and depression may interact to promote inflammation in pregnancy (Okun, Luther, Wisniewski, & Wisner, 2013). In contrast, Blackmore et al. (2011) found that although depressive symptoms were not associated with inflammation, a history of trauma predicted elevations in TNF-α during pregnancy. These findings indicate that pregnant women with particular psychological risk factors may experience higher daily exposure to inflammatory mediators. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Maternal psychosocial stress during pregnancy is associated with risks to maternal health, birth outcomes, as well as adverse health and behavioral outcomes in offspring. Maternal immune dysregulation, particularly disruption of inflammatory processes, is also implicated in adverse perinatal health outcomes, with the greatest evidence in relation to preterm birth. Increasingly, the extent to which psychosocial stress induces dysregulation of inflammatory processes during pregnancy is being considered. In this article, I describe studies linking stress to immune function during pregnancy, with an emphasis on studies from our group on inflammation. As will be reviewed, research utilizing psychoneuroimmunology models in pregnancy is a rapidly developing area with abundant opportunities to address questions of clinical relevance for both maternal and child health.
    Full-text · Article · Feb 2015 · Current Directions in Psychological Science
  • Source
    • "Recent work has begun to address how these factors may contribute to the effects of stress on pregnancy (Cowchock et al., 2011; Dunkel Schetter, 2011). Studies have shown, for example, that trauma and depression before and during pregnancy contribute to adverse pregnancy outcomes, may predispose women to the negative biological effects of prenatal stress, and are heightened in minority women who experience race-based stress (Blackmore et al., 2011; Cassidy-Bushrow, Peters, Johnson, & Templin, 2012; Christian, Franco, Glaser, & Iams, 2009). As researchers continue to unravel how different sources of stress, maternal race and culture, and individual differences interact to affect pregnancy, other investigators are examining the biological mechanisms through which these factors may translate into an increased risk of adverse pregnancy outcomes. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The rate of preterm birth in the United States remains high. In up to 40% of cases of preterm birth, the mothers are healthy women who have no clear risk factors. Accordingly, research has begun to explore the effect of prenatal stress on the risk of preterm birth and shortened gestational age at birth. There is increasing evidence that psychosocial stress throughout gestation increases the risk of preterm birth through changes in maternal endocrine, immune, and inflammatory activity during pregnancy. In this article, I describe foundational and current research examining the effects and biological mechanisms of prenatal stress in preterm birth and shortened gestational age at birth. I emphasize psychoneuroimmunology-focused studies showing that prenatal stress alters inflammatory and endocrine markers during gestation and that these changes are associated with preterm birth and shortened gestational age at birth.
    Full-text · Article · Oct 2012 · Current Directions in Psychological Science
Show more