Are alterations in estradiol, cortisol, and inflammatory cytokines associated with depression during pregnancy and postpartum? An exploratory study

Abstract

Background Pregnant veterans are a subpopulation known to be at elevated risk of developing mental health symptoms, such as depression and suicidal ideation. Inflammation has been associated with depression, specifically during the perinatal period. Critical changes in estradiol, cortisol, and inflammatory cytokines are necessary for the progression of a healthy pregnancy, which are then rapidly altered in the postpartum period. We explored changes in estradiol, cortisol, and pro-inflammatory cytokines relative to depressive symptoms and suicidal thoughts across pregnancy and postpartum in this pilot and feasibility study. Methods We measured estradiol, cortisol, and the inflammatory cytokines IL-1β, IL-6, IL-8, IFN-γ, and TNF-α in 18 pregnant veterans and analyzed the data using descriptive statistics, dependent t-tests, and correlation analyses. We assessed depression severity with the Edinburgh Postnatal Depression Scale and suicidality with the Columbia-Suicide Severity Rating Scale. Thirteen of the women repeated assessments in the early postpartum period at an average of 6.7 weeks after birth. Results As anticipated, estradiol ( t (12) ​= ​12.47, p ​< ​.001) and cortisol ( t (12) ​= ​9.43, p ​< ​.001) significantly decreased from pregnancy to postpartum. There were no differences in the means of gestational and postpartum IL-1β, IL-6, TNF-α, or IFN-γ, but IL-8 was significantly increased from pregnancy to postpartum ( t (12) ​= ​−4.60, p ​= ​.001). Estradiol during pregnancy was positively correlated with IL-6 levels both during pregnancy ( r p ​= ​.656, p ​= ​.008) and postpartum ( r ​= ​0.648, p ​= ​.023). Elevated IL-1β was associated with suicidal thoughts during pregnancy ( r ​= ​0.529, p ​= ​.029). Although not statistically significant, depressive symptom severity trended towards a positive association with larger increases in IL-1β ( r ​= ​0.535, p ​= ​.09) and TNF-α ( r ​= ​0.501, p ​= ​.08) from pregnancy to postpartum. Conclusion This preliminary study suggests the feasibility of our approach for exploring a complex interplay between hormonal and pro-inflammatory changes from pregnancy to postpartum, and their relationship with depressive symptoms. Given our small sample and the relatively exploratory nature of our analyses, additional investigation focusing on hormonal and inflammatory changes and their potential associations with perinatal mental health is necessary to confirm and extend our preliminary findings and examine additional potential cova...

Association of pica with cortisol and inflammation among Latina pregnant women

“…Because cortisol is associated with immunosuppression in pregnancy, it was unlikely that both our hypotheses would have been, simultaneously, true, that pica would be correlated with both higher cortisol and higher inflammation; therefore, our study may distinguish between these two possibilities. These two physiological states tend not to co‐exist, although some studies have found no correlation between maternal prenatal cortisol and inflammation (Nazzari et al, 2020; Szpunar et al, 2021) and both have been associated with prenatal mood disorders (Christian et al, 2009; Haeri et al, 2013; Osborne et al, 2019; Schweizer‐Schubert et al, 2021).…”

Inflammatory pathophysiological mechanisms implicated in postpartum depression

“…Other studies ( Ahn and Corwin, 2015 ; Nagayasu et al, 2021 ) did not find the correlation between IL-6 levels and the scores of Edinburgh Postpartum Depression Scale (EPDS), depressive symptoms, or stress variables. In an exploratory study among postpartum veterans ( Szpunar et al, 2021 ), the researchers found that elevated IL-1β and tumor necrosis factor-α (TNF-α) might have a positive correlation with the severity of depressive symptom. And the high level of IL-1β was also related to suicidal thoughts during pregnancy ( Szpunar et al, 2021 ).…”

“…In an exploratory study among postpartum veterans ( Szpunar et al, 2021 ), the researchers found that elevated IL-1β and tumor necrosis factor-α (TNF-α) might have a positive correlation with the severity of depressive symptom. And the high level of IL-1β was also related to suicidal thoughts during pregnancy ( Szpunar et al, 2021 ). Similarly, other studies showed that uric or plasmic IL-1β was increased in mothers with depressive symptoms or high scores of EPDS (≥13) ( Corwin et al, 2008 ; Sha et al, 2022 ).…”

“…Serumal interferon-γ (IFN-γ) and the ratio of IFN-γ/IL-10 were decreased in PPD, according to Maureen W Groer et al ( Groer and Morgan, 2007 ). Besides, the secretion of IL-8 has been reported to increase in the postpartum period ( Szpunar et al, 2021 ). Increased plasma IL-8 or reduced IL-2 was associated with higher risk for PPD ( Achtyes et al, 2020 ).…”

Editorial commentary on the special issue emerging psychoneuroimmunology research: Future leaders in focus

“…The use of objective measures, such as biomarkers, was identified as an important tool to help identify women at risk for postpartum depression ( Fransson, 2021 ) . In line with these suggestions, Szpunar et al. (2021) explored the complex relationships between estradiol, inflammatory markers (e.g., interleukin (IL)-1β and IL-6), cortisol, and depressive symptoms across both pregnancy and the postpartum period.…”