Larger Amygdala Volume Mediates the Association Between Prenatal Maternal Stress and Higher Levels of Externalizing Behaviors: Sex Specific Effects in Project Ice Storm

Abstract

Introduction: The amygdala is a brain structure involved in emotional regulation. Studies have shown that larger amygdala volumes are associated with behavioral disorders. Prenatal maternal depression is associated with structural changes in the amygdala, which in turn, is predictive of an increase in behavioral problems. Girls may be particularly vulnerable. However, it is not known whether disaster-related prenatal maternal stress (PNMS), or which aspect of the maternal stress experience (i.e., objective hardship, subjective distress, and cognitive appraisal), influences amygdala volumes. Nor is it known whether amygdala volumes mediate the effect of PNMS on behavioral problems in girls and boys. Aims: To assess whether aspects of PNMS are associated with amygdala volume, to determine whether timing of exposure moderates the effect, and to test whether amygdala volume mediates the association between PNMS and internalizing and externalizing problems in 11½ year old children exposed in utero , to varying levels of disaster-related PNMS. Methods: Bilateral amygdala volumes (AGV) and total brain volume (TBV) were acquired using magnetic resonance imaging, from 35 boys and 33 girls whose mothers were pregnant during the January 1998 Quebec Ice Storm. The mothers' disaster-related stress was assessed in June 1998. Child internalizing and externalizing problems were assessed at 11½ years using the Child Behavior Checklist (CBCL). Hierarchical regression analyses and mediation analyses were conducted on boys and girls separately, controlling for perinatal and postnatal factors. Results: In boys, subjective distress was associated with larger right AGV/TBV when mothers where exposed during late pregnancy, which in turn explained higher levels of externalizing behavior. However, when adjusting for postnatal factors, the effect was no longer significant. In girls, later gestational exposure to the ice storm was associated with larger AGV/TBV, but here, higher levels of objective PNMS were associated with more externalizing problems, which was, in part, mediated by larger AGV/TBV. No effects were detected on internalizing behaviors. Conclusion: These results suggest that the effects of PNMS on amygdala development and externalizing symptoms, as assessed in boys and girls in early adolescence, can be influenced by the timing of the stress in pregnancy, and the particular aspect of the mother's stress experience.

Prenatal and postnatal maternal anxiety and amygdala structure and function in young children

“…The relationship remained significant after controlling for total brain volume but did not survive FDR correction. Previous studies have shown that higher prenatal maternal stress and depression are associated with larger amygdala volume in children aged 4.5–11 years 13 , 27 . Furthermore, higher levels of cortisol in early pregnancy, which typically reflect higher stress, have been associated with larger right amygdala volume in children aged 7 years 9 .…”

“…Previous studies relating maternal mental health during the second trimester (14–26 weeks gestation) and postpartum to child brain structure and function 14 , 16 , 27 , 28 provide a rationale for examining anxiety symptoms at these time points. Early childhood is a time of extensive brain development 29 and a time when the behaviour problems associated with prenatal maternal anxiety often emerge 8 , 29 , which suggests looking at children’s brains during this time could provide important insight into how maternal anxiety could impact child brain development.…”

Association of Prenatal Maternal Anxiety With Fetal Regional Brain Connectivity

“…12 Postnatal brain imaging findings have provided insights into potential neural substrates for these deficits. These include reduced cortical thickness, 13,14 amygdala and hippocampal volume changes, [15][16][17] asymmetric electroencephalographic patterns in the frontal lobes, 18,19 white matter microstructural changes, 20,21 and impaired connectivity. 22,23 More recently, a study by Wu and colleagues 24 provided, to our knowledge, the first report of impaired brain metabolism, reduced hippocampal growth, and accelerated cortical folding in fetuses of women experiencing psychological distress.…”

Upregulation of spinal ASIC1 by miR‐485 mediates enterodynia in adult offspring rats with prenatal maternal stress

“…Therefore, prenatal maternal stress (PMS) model was used in the present study to further explore mechanisms of early life stress on enterodynia. At present, many studies have been focused on the effects of stressors on the brain areas such as amygdale or the peripheral nervous system such as dorsal root ganglia (DRG) of the offspring 9,10 . Relatively few studies are focused on the spinal dorsal horn.…”

“…At present, many studies have been focused on the effects of stressors on the brain areas such as amygdale or the peripheral nervous system such as dorsal root ganglia (DRG) of the offspring. 9,10 Relatively few studies are focused on the spinal dorsal horn. The spinal cord is the first relay area of sensory information from the periphery to the center.…”