Heterogeneity of Maternal Psychological Stress During Pregnancy and its Associations with Offspring Amygdala Connectivity and Negative Affect Development

• In Event: From psychological to environmental risk mechanisms: Advancing the study of prenatal influences on biobehavioral development

Abstract

Background: Maternal psychological stress during pregnancy is a common and potentially modifiable risk factor for offspring psychiatric disorders. Here we employ novel, data-driven methods to investigate heterogeneity in maternal psychological stress during pregnancy, and associations with infant brain and behavioral development.
Methods: Maternal psychological stress was assessed across pregnancy and early postpartum in two independent mother-infant dyad cohorts (Total N=2,271). Maternal perinatal stress trajectories were characterized and grouped into clusters using a novel machine learning algorithm, the Functional Random Forest. Across both samples, maternal stress trajectories were examined in relationship to infant negative affect. Neonatal amygdala resting-state functional connectivity MRI was examined in the sample with neuroimaging data.
Outcomes: In the original sample, four distinct clusters characterized by differences in the pattern of change over time (trajectory), and two characterized by overall magnitude of stress (higher versus lower) were identified. The magnitude clusters were not associated with infant brain or behavioral outcomes. In contrast, the trajectory cluster characterized by increasing stress in late pregnancy was associated with a smaller increase in infant negative affect from 3 to 24 months (M = −0.927, p = 0.04) and stronger amygdala to ventromedial prefrontal cortex resting state functional connectivity (B = 0.441, p = 0.03). The trajectory cluster characterized by peak stress in late pregnancy was associated with stronger amygdala to anterior insula (B = 0.471, p = 0.02) and amygdala to ventromedial prefrontal cortex (B = 0.507, p = 0.02) resting state functional connectivity. The maternal trajectory clusters were replicated in an independent sample. Consistent with the results from the original cohort, maternal trajectory clusters showed a significant main effect of group on infant negative affect over time (F=3·04, p=0·028).

Interpretation: In this cohort study of mothers and their infants, we found associations between the trajectory of maternal psychological stress during the perinatal period and negative affect in offspring out to 2-years of age using a novel machine learning algorithm. Patterns of offspring amygdala functional connectivity were also affected by maternal stress trajectories in offspring. In other words, the trajectory, as opposed to the magnitude, of perinatal stress appears to be critical in determining how maternal psychological stress during pregnancy affects offspring brain and behavioral development. Stress late in pregnancy appears to be a highly sensitive time with effects on increased neonatal amygdala functional connectivity and negative affect development lasting over the first two years of life. Understanding the heterogeneity of perinatal stress trajectories and their influence on infant brain and behavioral development is critical to targeting future interventions.

Authors

• Mollie Marr, Oregon Health & Science University (OHSU)
  Presenting Author

• Alice M. Graham, Oregon Health and Science University
  Non-Presenting Author

• Eric Feczko, University of Minnesota
  Non-Presenting Author

• Saara Nolvi, University of Turku
  Non-Presenting Author

• Elina Thomas, Oregon Health & Science University
  Non-Presenting Author

• Darrick Sturgeon, Oregon Health & Science University
  Non-Presenting Author

• Emma Schifsky, Oregon Health & Science University
  Non-Presenting Author

• Jerod M. Rasmussen, University of California, Irvine
  Non-Presenting Author

• John H. Gilmore, University of North Carolina at Chapel Hill
  Non-Presenting Author

• Martin Styner, University of North Carolina at Chapel Hill
  Non-Presenting Author

• Sonja Entringer, Charité University of Medicine Berlin
  Non-Presenting Author

• Pathik D. Wadhwa, University of California, Irvine
  Non-Presenting Author

• Riikka Korja, University of Turku
  Non-Presenting Author

• Hasse Karlsson, Turku University Hospital and University of Turku
  Non-Presenting Author

• Linnea Karlsson, University of Turku
  Non-Presenting Author

• Claudia Buss, Charité University of Medicine Berlin
  Non-Presenting Author

• Damien A. Fair, University of Minnesota - Twin Cities
  Non-Presenting Author