Maternal prenatal depression is associated with dysregulation over the first five years of life moderated by child polygenic risk for comorbid psychiatric problems

Abstract

Dysregulation is a combination of emotion, behavior, and attention problems associated with lifelong psychiatric comorbidity. There is evidence for the stability of dysregulation from childhood to adulthood, which would be more fully characterized by determining the likely stability from infancy to childhood. Early origins of dysregulation can further be validated and contextualized in association with environmental and biological factors, such as prenatal stress and polygenic risk scores (PRS) for overlapping child psychiatric problems. We aimed to determine trajectories of dysregulation from 3 months to 5 years (N = 582) in association with maternal prenatal depression moderated by multiple child PRS (N = 232 pairs with available PRS data) in a prenatal cohort. Mothers reported depression symptoms at 24-26 weeks' gestation and child dysregulation at 3, 6, 18, 36, 48, and 60 months. The PRS were for major depressive disorder, attention deficit hyperactivity disorder, cross disorder, and childhood psychiatric problems. Covariates were biological sex, maternal education, and postnatal depression. Analyses included latent classes and regression. Two dysregulation trajectories emerged: persistently low dysregulation (94%), and increasingly high dysregulation (6%). Stable dysregulation emerged at 18 months. High dysregulation was associated with maternal prenatal depression, moderated by PRS for child comorbid psychiatric problems. Males were at greater risk of high dysregulation.

Prenatal maternal stress: triangulating evidence for intrauterine exposure effects on birth and early childhood outcomes across multiple approaches

“…Since recent evidence has accumulated to show that common genetic variants have largely non-speci c and highly overlapping associations with complex behavioral traits (39)(40)(41), this pathway is highly likely to be relevant for links between prenatal stress and offspring emotional and behavioral outcomes. Aside from a few notable exceptions (42)(43)(44)(45)(46)(47), most studies have not employed causally informative and genetically informed designs to explore the associations between prenatal stress, including mental health factors, and offspring emotional and behavioral outcomes. Most studies controlling for this pathway suggest either a lack of association between prenatal exposure and child outcomes (45,48), or that association strength depends on the child's genetic susceptibility (42)(43)(44).…”

“…Aside from a few notable exceptions (42)(43)(44)(45)(46)(47), most studies have not employed causally informative and genetically informed designs to explore the associations between prenatal stress, including mental health factors, and offspring emotional and behavioral outcomes. Most studies controlling for this pathway suggest either a lack of association between prenatal exposure and child outcomes (45,48), or that association strength depends on the child's genetic susceptibility (42)(43)(44). Several of these studies suggest that prenatal exposure to stress, anxiety, or depression does not directly cause emotional and behavioral di culties in offspring (43)(44)(45)48).…”