Maternal prenatal depression predicts infant negative affect via maternal inflammatory cytokine levels

Abstract

Maternal depressive symptoms during pregnancy are associated with risk for offspring emotional and behavioral problems, but the mechanisms by which this association occurs are not known. Infant elevated negative affect (increased crying, irritability, fearfulness, etc.) is a key risk factor for future psychopathology, so understanding its determinants has prevention and early intervention potential. An understudied yet promising hypothesis is that maternal mood affects infant mood via maternal prenatal inflammatory mechanisms, but this has not been prospectively examined in humans. Using data from a pilot study of women followed from the second trimester of pregnancy through six months postpartum (N = 68) our goal was to initiate a prospective study as to whether maternal inflammatory cytokines mediate the association between maternal depressive symptoms and infant offspring negative affect. The study sample was designed to examine a broad range of likely self-regulation and mood-regulation problems in offspring; to that end we over-selected women with a family history or their own history of elevated symptoms of attention-deficit/hyperactivity disorder. Results supported the hypothesis: maternal pro-inflammatory cytokines during the third trimester (indexed using a latent variable that included plasma interleukin-6, tumor necrosis factor-alpha and monocyte chemoattractant protein-1 concentrations as indicators) mediated the effect, such that higher maternal depressive symptoms were associated with higher maternal inflammation, and this mediated the effect on maternal report of infant negative affect (controlling for maternal affect during the infant period). This is the first human study to demonstrate that maternal inflammatory cytokines mediate the association between prenatal depression and infant outcomes, and the first to demonstrate a biological mechanism through which depressive symptoms impact infant temperament.

Association between preeclampsia and autism spectrum disorder: a population‐based study

“…All ASD (n = 54,071) stratified by ASD with intellectual disability, as elevated midgestational levels of numerous cytokines and chemokines such as GM-CSF, IFN-c, IL-1a and IL-6 are associated with ASD with intellectual disability, when compared to mothers of children with either ASD without intellectual disability, developmental delay or general population controls (Jones et al, 2017). In terms of mediation, while very little data exist in humans, a recent study has shown that maternal depressive symptoms are associated with higher maternal inflammation, including IL-6, and this mediated the effect on maternal report of infant negative affect (Gustafsson et al, 2018), a known risk factor for later adverse neurological outcomes. This may also suggest that preeclampsia-induced elevations in maternal IL-6 may act as a mediator of the preeclampsia-ASD association.…”

Maternal depression and inflammation during pregnancy

“…Online Supplementary Table ST2 provides further details of the NOS assessment and criteria for cross-sectional (Herzog et al, 2013;Anthony and Lin, 2018) and online Supplementary Table ST3 for cohort studies (Wells et al, 2014a(Wells et al, , 2014b. The NOS assessment of the reviewed studies highlights the limited quality of available evidence: of the 10 reviewed studies 40% were defined as 'poor' (Scrandis et al, 2008;Azar and Mercer, 2013;Cheng and Pickler, 2014;Gustafsson et al, 2018), 50% as 'fair' (Christian et al, 2009;Cassidy-Bushrow et al, 2012;Haeri et al, 2013;Simpson et al, 2016;Osborne et al, 2018), and 10% as 'good' (Blackmore et al, 2011) based on the NOS assessment. Online Supplementary Table ST1 also shows that the findings are mixed with some studies showing that maternal depression is associated with higher levels of a number of inflammatory markers studied and some reporting null associations.…”

Priorities in stress research: a view from the U.S. National Institute of Mental Health

“…Genomic factors, such as inherited genetic risk, and epigenetic modifiers influence stress neurobiology in model systems and in humans. Immune activation differences resulting from prior exposures can regulate the neural and behavioral impact of subsequent stressors (Kerr et al, 2005;Clark et during pregnancy could not only alter maternal hypothalamic pituitary adrenal axis (HPA) axis and immune function, but also shape neurodevelopmental trajectories and stress responsiveness in offspring (Ja sarevi c et al, 2017;Carlson et al, 2018;Davidson et al, 2018;Gustafsson et al, 2018;Rasmussen et al, 2019;Spann et al, 2018;Thompson et al, 2018;Graham et al, 2019).…”