The current data provide evidence that depressive symptoms predict sensitization of inflammatory responses to an in vivo immune challenge during pregnancy. Women scoring in the highest tertile of depressive symptoms as measured by the CES-D exhibited significantly higher MIF at one week following influenza virus vaccination as compared to women in the lowest tertile. Groups did not differ in demographic characteristics (e.g., age, BMI, race, income) or health behaviors (e.g., sleep, smoking, regular exercise) assessed, suggesting that these factors did not account for the effects of depressive symptoms.
The absence of an increase in MIF levels at one week post-vaccination among women with lower depressive symptoms is consistent with previous evidence that influenza virus vaccination does not generally cause an extended inflammatory response (Glaser et al., 2003
; Posthouwer et al., 2004
; Tsai et al., 2005
). Thus, we suggest that the inflammatory response seen among the more depressed individuals at one week post-vaccination indicates dysregulation of normal inflammatory processes.
These data have important implications for understanding risk of negative perinatal outcomes. As described previously, inflammatory responses to infection during pregnancy are implicated in outcomes relevant to maternal health, preterm delivery, and fetal development. Women who experience greater depressive symptoms during pregnancy may experience greater inflammatory responses upon exposure to other immune challenges including infectious agents, putting them at greater risk for negative sequelae. Relatedly, inflammatory responses to influenza vaccination are mild as compared to responses to influenza infection (e.g., Hayden et al., 1998
; Tsai et al., 2005
), supporting the clinical utility of vaccination.
Evidence also suggests that individuals experiencing greater stress are more susceptible to infection. For example, chronic stress among pregnant women has been associated with approximately two times greater risk of bacterial vaginosis (BV) (Culhane et al., 2001
). Therefore distress may contribute to inflammation during pregnancy by increasing both susceptibility and response to infectious agents.
To our knowledge, there are no prior studies examining whether distress predicts priming of MIF responses to biological challenge. However, data from animal models indicates that MIF rises in response to acute behavioral stress (Calandra et al., 1995
) and elevations in MIF have previously been associated with depressive symptoms among young men (Hawkley et al., 2006
) and pregnant women (Pearce, 2004
In the current investigation, depressive symptoms did not predict differences in MIF prior to vaccination, although a trend towards this effect equivalent to a medium effect size was suggested. Thus, additional research with a larger sample size is needed to confirm the present results and to further examine associations of depressive symptoms with MIF prior to vaccination.
Although the CES-D is a valid and reliable measure of depressive symptomatology, it does not allow for diagnosis of clinical depression. It is estimated that 40–50% of those scoring at or above the commonly used cut-off of 16 on the CES-D meet criteria for major depression as determined by clinical interview (Weissmann et al., 1977
). A variety of higher cut-offs have been suggested to provide greater specificity and to identify more severe cases (e.g., Radloff, 1991
). In the current sample, exaggerated inflammatory responses were seen among those scoring in the top third (≥ 22). Research in which diagnostic clinical interviews are utilized in conjunction with questionnaire measures would allow for better determination of the predictive validity of assessing depressive symptoms versus clinical depression. Also, in the current study, three women classified as the highest tertile of depressive symptoms reported that they had previously been diagnosed with and treated for a mood disorder. The study sample size did not allow for analyses of effects of current versus recurrent depressive symptoms which could be addressed in a larger sample with more comprehensive assessment of psychiatric history.
Of note, our ability to detect effects of interest within a small sample was largely a function of the notably high rate of depressive symptoms in our study population. This rate was similar to other studies of pregnant women from lower socioeconomic backgrounds, highlighting the importance of delineating effects of depressive symptoms during pregnancy. For example, Seguin and colleagues (1995)
found that 47% of pregnant women whose incomes were below the poverty line scored at or above a clinical cut-off for depressive symptoms as compared to 20% of pregnant women from higher socioeconomic backgrounds.
The current study does not address the dynamics of change in MIF over time. The follow-up timepoint of one week post-vaccination was selected to capture relatively extended inflammatory responses; because prolonged responses are not generally expected in the context of vaccination, such responses may provide an indication of immune dysregulation. However, research examining the dynamics of inflammatory responses over time, including timepoints more immediately post-vaccination, would be highly informative. In addition, the extent to which inflammatory responses to vaccination predict health outcomes (e.g., preterm delivery, preeclampsia, antibody response to vaccination) should be addressed in future studies.
These data do not allow for examination of the effects of stage of pregnancy on inflammatory responses. In addition, because effects of depressive symptoms during pregnancy were of primary interest, a nonpregnant comparison group was not included in this study. Future research utilizing a larger sample size and more comprehensive assessment of health behaviors will allow for more thorough analysis of demographic and behavioral factors which may mediate and/or moderate effects noted in the current investigation.
In sum, the current data provide evidence that depressive symptoms predict exaggerated inflammatory responses to an in vivo antigen challenge during pregnancy. These findings implicate a novel and plausible pathway by which depressive symptoms may affect maternal health (e.g., preeclampsia), pregnancy outcomes (e.g., preterm delivery), and offspring health.