Stress-Related Mental Health Disorders and Inflammation in Pregnancy: The Current Landscape and the Need for Further Investigation

Abstract

Many studies have focused on psychoimmunological mechanisms of risk for stress-related mental health disorders. However, significantly fewer studies have focused on understanding mechanisms of risk for stress-related disorders during pregnancy, a period characterized by dramatic changes in both the innate and adaptive immune systems. The current review summarizes and synthesizes the extant literature on the immune system during pregnancy, as well as the sparse existing evidence highlighting the associations between inflammation and mood, anxiety, and fear-related disorders in pregnancy. In general, pregnant persons demonstrate lower baseline levels of systemic inflammation, but respond strongly when presented with an immune challenge. Stress and trauma exposure may therefore result in strong inflammatory responses in pregnant persons that increases risk for adverse behavioral health outcomes. Overall, the existing literature suggests that stress, trauma exposure, and stress-related psychopathology are associated with higher levels of systemic inflammation in pregnant persons, but highlight the need for further investigation as the existing data are equivocal and vary based on which specific immune markers are impacted. Better understanding of the psychoimmunology of pregnancy is necessary to reduce burden of prenatal mental illness, increase the likelihood of a successful pregnancy, and reduce the intergenerational impacts of prenatal stress-related mental health disorders.

Keywords: inflammation; mental health; pregnancy; stress; women's health.

Figure 1

(A) Under normal conditions, monocytes produce low concentrations of pro-inflammatory cytokines including TNFα, IL-12, and IL-18. Simultaneously, pregnancy is characterized by shift that reduces the proportion of NK1 (IL-18R1) cells in circulation. Existing NK1 cells are weakly stimulated by low concentrations of IL-18, resulting in low production of IFN-γ, ultimately resulting in more M2 decidual macrophages and a less pro-inflammatory environment that characterizes the second and third trimesters of healthy pregnancies. (B) Under conditions of chronic stress, monocytes are stimulated at higher rates, resulting in greater production of pro-inflammatory cytokines, including IL-18. Higher concentrations of IL-18 activate NK1 cells at higher rates than under healthy conditions, leading to increased production of IFN-γ, which can promote an M1 over M2 bias in the decidua. When monocytes in pregnant individuals are stimulated in the presence of IFN-γ, the pro-inflammatory response is exaggerated, leading to even higher concentrations of pro-inflammatory cytokines, which could result in a pro-inflammatory bias in individuals experiencing chronic stress.