Prenatal maternal depression is associated with offspring inflammation at 25 years: a prospective longitudinal cohort study.

D T Plant,C M Pariante,S Pawlby,D Sharp,P A Zunszain

doi:10.1038/tp.2015.155

D T Plant, C M Pariante + Show 3 more

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https://doi.org/10.1038/tp.2015.155

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Abstract

Animal studies and a handful of prospective human studies have demonstrated that young offspring exposed to maternal prenatal stress show abnormalities in immune parameters and hypothalamic–pituitary–adrenal (HPA) axis function. No study has examined the effect of maternal prenatal depression on offspring inflammation and HPA axis activity in adulthood, nor the putative role of child maltreatment in inducing these abnormalities. High-sensitivity C-reactive protein (hs-CRP) and awakening cortisol were measured at age 25 in 103 young-adult offspring of the South London Child Development Study (SLCDS), a prospective longitudinal birth cohort of mother–offspring dyads recruited in pregnancy in 1986. Maternal prenatal depression was assessed in pregnancy at 20 and 36 weeks; offspring child maltreatment (birth 17 years) was assessed at offspring ages 11, 16 and 25; and offspring adulthood depression (18–25 years) was assessed at age 25. Exposure to maternal prenatal depression predicted significantly elevated offspring hs-CRP at age 25 (odds ratio=11.8, 95% confidence interval (CI) (1.1, 127.0), P=0.041), independently of child maltreatment and adulthood depression, known risk factors for adulthood inflammation. In contrast, maternal prenatal depression did not predict changes in offspring adulthood cortisol; however, offspring exposure to child maltreatment did, and was associated with elevated awakening cortisol levels (B=161.9, 95% CI (45.4, 278.4), P=0.007). Fetal exposure to maternal depression during pregnancy has effects on immune function that persist for up to a quarter of a century after birth. Findings are consistent with the developmental origins of health and disease (DOHaD) hypothesis for the biological embedding of gestational psychosocial adversity into vulnerability for future physical and mental illness.

Highlights

There is mounting evidence that many psychiatric and physical health conditions originate in adverse early-life experiences, but the exact timing for the embedding of such adverse experiences into the individual’s pathophysiology remains unknown, especially in regards to the relative contributions of prenatal and childhood environments
Inflammation was negatively correlated with cortisol-awakening response (CAR), as indexed by a significant negative correlation between High-sensitivity C-reactive protein (hs-C-reactive protein (CRP)) values and elevation in cortisol levels at 30 min post awakening
(controlling for gender, ethnicity, family social class, gestational comparison with non-exposed offspring, and offspring exposed to only child smoking, medication use and body mass index), maternal prenatal depression predicted significantly elevated offspring hs-CRP levels (B = 1.1, t = 2.9, P = 0.005, 95% confidence interval (CI) (0.3, 1.8), model R2 = .45, F11,63 = 4.6, Po 0.001, n = 75; see Supplementary Figure 1 for scatterplot)

Summary

Introduction

There is mounting evidence that many psychiatric and physical health conditions originate in adverse early-life experiences, but the exact timing for the embedding of such adverse experiences into the individual’s pathophysiology remains unknown, especially in regards to the relative contributions of prenatal and childhood environments. Much contemporary research has investigated the relationship between very early-life adversity, namely exposure to maternal prenatal stress, and neurodevelopmental and health outcomes in later life, including emotional, behavioral and cognitive psychopathology, stress physiology, brain plasticity, immune function and chronic metabolic diseases.[1,2,3,4,5,6,7,8] This body of research draws upon the theoretical premise of fetal programming, which posits that exposure to an adverse intrauterine environment, especially elevated levels of maternal glucocorticoids, can generate persistent changes in fetal biological systems, which subsequently confer risk for developmental disorders later in life.[9,10,11,12]. Depressed individuals exhibit elevated levels of peripheral blood inflammatory biomarkers, most commonly C-reactive protein (CRP) and proinflammatory cytokines, as well as plasma, salivary and urinary cortisol.[22,23,24,25,26,27] As pregnancy per se is associated with increased maternal inflammation and HPA axis activity,[28,29] which can be further exacerbated by the experience of depression during this time,[30] it has been hypothesized that inflammation and HPA axis dysregulation are likely candidate mechanisms for the biological embedding of maternal–fetal transmission of stress reactivity and vulnerability for affective psychopathology.[31,32,33,34]

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