The Biological Embedding of Early-life Adversity: Using Salivary Biomarkers to Examine the Influence of Maternal Psychological Well-being on Child Neuroendocrine-immune Functioning

Background: Neuroendocrine-immune (NEI) regulation is essential for maintaining health. Through repeated activation of the stress response, early-life adversity may lead to dysregulation of the NEI network and increase risk of inflammatory-related disease. Studying NEI functioning during childhood, however, has been limited by the need for biologic data, which has been largely restricted to blood-based measures. Objectives: Using salivary biomeasures of immune activity (cytokines) this study examined: 1) the nature and correlates of salivary cytokines in children; and 2) the role of early-life adversity in moderating child NEI functioning. Methods: Data were drawn from the Fetus to Five study, a laboratory-based study of mother-child pairs. Children participated in stress-inducing tasks and provided four saliva samples. Mothers completed a survey about child health, family sociodemographics, and maternal mental health. Saliva was assayed for four inflammatory cytokines (IL-1β, IL-6, IL-8, TNFα) and markers of autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) activity (alpha-amylase (sAA), cortisol). Multilevel mixed models examined relations between cytokines and child health and demographic factors, and associations with sAA and cortisol. Composite scores reflecting socioeconomic status (SES) and maternal distress were created for each child using factor analysis of SES and maternal psychological (depressive symptoms, anxiety, stress) variables. Multilevel mixed models for cortisol examined child cortisol-cytokine relations and interactions between maternal distress and cytokines on cortisol, adjusting for SES. Results: Cytokines were largely unrelated to health and demographic factors, but were associated with oral health measures. Among boys, cytokines were positively associated with sAA and inversely associated with cortisol. In the full sample, positive maternal distress-cytokine interactions on cortisol for IL-1β, IL-6 and TNFα indicated that as maternal distress increased, inverse cytokine-cortisol relations became weaker. These interactions were driven by significant interactions among girls. Conclusions: Salivary cytokines in children reflect oral immune processes. Relations between cytokines and markers of ANS and HPA activity in saliva, however, mirror those in serum, suggesting NEI functioning may be studied using salivary biomeasures. Among girls, regardless of SES, maternal distress was associated with less efficient regulation of child inflammatory activity by cortisol. This desensitization may increase inflammatory-related disease risk and contribute to health disparities