Abstract

Prenatal exposure to maternal depression increases the risk for onset of emotional and behavioral disorders in children. We investigated the effects of exposure to prenatal depression on white matter microstructural integrity at birth and at 2-3 years, and associated neurodevelopment. Diffusion-weighted images were acquired for children of the Drakenstein Child Health Study at 2-4 weeks postpartum (n=70, 47% boys) and at 2-3 years of age (n=60, 58% boys). Tract-Based Spatial Statistics was used to compare, using an ROI based approach, diffusion tensor metrics across groups defined by presence (>19 on Beck’s Depression Inventory and/or >12 on the Edinburgh Postnatal Depression Scale) or absence (below depression thresholds) of depression, and associations with neurodevelopmental measures at age 2-3 years were determined. We did not detect group differences in white matter integrity at neonatal age, but at 2-3 years, children in the exposed group demonstrated higher fractional anisotropy, and lower mean and radial diffusivity in association tracts compared to controls. This was notable in the sagittal stratum (radial diffusivity: p<0.01). Altered white matter integrity metrics were also observed in projection tracts, including the corona radiata, which associated with cognitive and motor outcomes in exposed 2-3-year-olds (p<0.05). Our findings of widespread white matter alterations in 2-3-year-old children with prenatal exposure to depression are consistent with previous findings, as well as with neuroimaging findings in adults with major depression. Further, we identified novel associations of altered white matter integrity with cognitive development in depression-exposed children, suggesting that these neuroimaging findings may have early functional impact.

Highlights

  • Depression remains a prevalent and debilitating condition, affecting 264 million of the world’s population of all ages (Depression, 2020)

  • The burden of perinatal depression is higher in low-to-middle income countries (LMIC) where multiple risk factors impact on quality of life (Pellowski et al, 2019; Woody et al, 2017)

  • The aim of this study is to determine the effects of prenatal depression exposure (PDE) on white matter microstructural integrity in children followed from birth to 2-3 years of age, in the Drakenstein Child Health Study (DCHS) birth cohort situated in a LMIC setting, and to examine associations with neurodevelopmental markers

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Summary

Introduction

Depression remains a prevalent and debilitating condition, affecting 264 million of the world’s population of all ages (Depression, 2020). An emerging literature suggests that prenatal exposure to maternal psychosocial distress, which includes depression, may impact the development of brain networks in exposed children, with associated increased risk for later behavioral and mental disorders (Scheinost et al, 2017; Van Den Bergh et al, 2018). Maternal depression during pregnancy (PDE), has a reported association with emotional and behavioral disorders in children. Research has recently started to identify relationships between maternal mood during pregnancy, fetal physiological programming, including alterations in both HPA axis and immune system, and later child psychopathology (Glover et al, 2018; Monk et al, 2019). PDE has been reported to impact early general physical health in exposed children, predicting subsequent healthrelated stress, depression, and impaired social functioning at age 20 years (Raposa et al, 2014)

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