Maternal Prenatal Distress and Child ADHD: Biological and Developmental Mechanisms of Risk

• In Event: Prenatal Distress and Neurobehavior in Infancy and Early Childhood: Testing Putative Biological Mechanisms

Abstract

Introduction: Previous research suggest that maternal prenatal psychological distress (symptoms of stress, depression, anxiety) is associated with increased risk for neurodevelopmental disorders in offspring, including ADHD (Monk et al., 2019; Rodriguez et al., 2005). However, the mechanisms through which this effect occurs are poorly understood. Stress-related increases in maternal inflammation during pregnancy are one hypothesized yet underexplored pathway (Glover, 2019); increased levels of maternal pro-inflammatory cytokines have been shown to influence fetal brain development in ways that may confer risk for mental health disorders. Early in life, this risk may present as increased infant negative affect, a dimension of temperament that has previously been linked with prenatal inflammation (Gustafsson et al., 2018), and which appears to be related to subsequent symptoms of ADHD (Rabinowitz et al., 2016, as hypothesized by Nigg et al., 2004). These two hypothesized and potentially linked mechanisms have not yet been considered prospectively together for their joint influence on child ADHD symptoms.

Hypotheses: Is the effect of maternal prenatal distress on child ADHD symptoms mediated by a) maternal inflammation, b) infant negative affect, and/or c) inflammation-associated increases in infant negative affect?

We tested this question using Structural Equation Modeling (SEM), where we uniquely tested for serial mediation (prenatal stress>inflammation>infant negative affect>child ADHD symptoms) while allowing for simple mediation effects.

Population: Pregnant women (N=68) were recruited during the second trimester and they and their offspring followed postpartum. In recruiting the sample, women with a childhood history or current elevated symptoms of ADHD were oversampled, to increase the likelihood of observing a full range of ADHD symptoms in the offspring.

Methods: Prenatal distress was measured using the CES-D (Radloff, 1977) and Perceived Stress Scale (Cohen et al., 1994), averaged across the 2nd and 3rd trimesters. Cytokine concentrations (interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α) were obtained in maternal plasma in the 3rd trimester. Six-month negative affect was assessed using the Infant Behavior Questionnaire (IBQ-R; Gartstein et al., 2003). Child ADHD symptoms were assessed when children were 4-6 years old, by parental report on the preschool version of the K-SAD (Gaffrey et al., 2012), the ADHD Rating Scale (DuPaul et al., 1998), SWAN (Swanson et al., 2012), and Strengths and Difficulties Questionnaire (Goodman, 2001). Hypotheses were tested using Mplus. Mediation was tested using the model indirect command in conjunction with bootstrapped 95% confidence intervals. Missing data were handled using FIML.

Results: Consistent with expectation, infant negative affect significantly mediated the effect of prenatal distress on child ADHD symptoms (β=-.29, p<.01), when considered in a model without maternal inflammation. Maternal inflammation also mediated the effect of prenatal distress on child ADHD symptoms, p<.05, when considered in a model without infant negative affect. Uniquely, we find evidence of serial mediation (β=.16, p<.05) (see Figure 1), such that the effect of prenatal distress on child ADHD symptoms operates via its influence on inflammation-linked negative affect in infancy.

These results provide novel insight into the biological and developmental mechanisms through which prenatal stress influences child risk for psychopathology.

Authors

• Hanna C Gustafsson, Oregon Health & Science University (OHSU)
  Presenting Author

• Jennifer Loftis, Oregon Health & Science University
  Non-Presenting Author

• Elinor L. Sullivan, Oregon Health & Science University (OHSU)
  Non-Presenting Author

• Joel T Nigg, Oregon Health & Science University (OHSU)
  Non-Presenting Author