Immune System Alterations and Postpartum Mental Illness: Evidence From Basic and Clinical Research

Abstract

The postpartum period is a time associated with high rates of depression and anxiety as well as greater risk for psychosis in some women. A growing number of studies point to aberrations in immune system function as contributing to postpartum mental illness. Here we review evidence from both clinical and animal models suggesting an immune component to postpartum depression, postpartum anxiety, and postpartum psychosis. Thus far, clinical data primarily highlights changes in peripheral cytokine signaling in disease etiology, while animal models have begun to provide insight into the immune environment of the maternal brain and how central inflammation may also be contributing to postpartum mental illnesses. Further research investigating peripheral and central immune function, along with neural and endocrine interactions, will be important in successfully developing novel prevention and treatment strategies for these serious disorders that impact a large portion of new mothers.

Sex differences in depression: An immunological perspective

“…A thorough review was performed on the nutrition and psychoneuroimmunology of postpartum depression that covers the topic well ( Ellsworth-Bowers and Corwin, 2012 ). Another noteworthy review covers how central and peripheral immune system dynamics change during and after pregnancy by studying available clinical research data ( Dye et al, 2022 ). Postpartum depression occurs in 15–20% of women as well as 8 10% of men ( Scarff, 2019 ).…”

Gestational stress decreases postpartum mitochondrial respiration in the prefrontal cortex of female rats

“…This finding replicates previous studies reporting a lack of correlation between central and peripheral immune activation (Boufidou et al, 2009; Miller et al, 2019) and further highlights the unique and complex nature of postpartum inflammation. Indeed, this complexity is further underlined by the conflicting reports on gestational stress-induced inflammation at both the central and peripheral levels in the rodent literature (Dye et al, 2022), possibly due to differences in the timing of measurement and stress protocols. Measurements taken at GD21 identified increased levels of IL-1β and Interferon gamma (IFN-γ) in the PFC of gestationally stressed females, but no changes in plasma cytokine levels from non-stressed pregnant counterparts (Lenz et al, 2019).…”

“…These behavioral outputs have been associated with molecular changes in inflammatory responses, hormone signaling, neuroplasticity, and neurotransmission (Brummelte and Galea, 2016;Corwin et al, 2015;McEwen et al, 2012;Pawluski et al, 2016Pawluski et al, , 2011Schiller et al, 2015). For example, stress-sensitive regions such as the prefrontal cortex (PFC), nucleus accumbens (NAc), and hippocampus (HPC) demonstrate structural changes and increased cytokine levels in animal models of postpartum depression (Dye et al, 2022;Haim et al, 2014;Leuner et al, 2014a;Workman et al, 2013). Additionally, the steroid hormone progesterone and its metabolite and neurosteroid, allopregnanolone, are associated with adaptation to stress (Brunton et al, 2014).…”

Risk of postpartum readmission for depression in relation to ischaemic placental disease: a population-based study

“… 4 Prior studies highlight biological associations such as hormonal sensitivity or role of steroid and stress hormones, 11 genetics, 12 hypothalamic-pituitary-adrenal (HPA) axis dysfunction, 13 changes in neurotransmitters, 14 oxidative stress or inflammation, 15 and immune-mediated pathways. 15 , 16 , 17 Recent studies have purported a possible increased risk of postpartum depression among patients that are diagnosed with preeclampsia. 18 , 19 Preeclampsia, a common complication affecting about 5% of all pregnancies, a likely consequence of uteroplacental ischaemia, has pathophysiological mechanisms that are common to both placental abruption and small for gestational age (SGA) births.…”