Prenatal Maternal Stress From a Natural Disaster and Hippocampal Volumes: Gene-by-Environment Interactions in Young Adolescents From Project Ice Storm.

Lei Cao-Lei,Guillaume Elgbeili,Sandra Yogendran,Romane Dufoix,Suzanne King,David P Laplante

doi:10.3389/fnbeh.2021.706660

Abstract

Gene-by-environment interactions influence brain development from conception to adulthood. In particular, the prenatal period is a window of vulnerability for the interplay between environmental and genetic factors to influence brain development. Rodent and human research demonstrates that prenatal maternal stress (PNMS) alters hippocampal volumes. Although PNMS affects hippocampal size on average, similar degrees of PNMS lead to different effects in different individuals. This differential susceptibility to the effects of PNMS may be due to genetic variants. Hence, we investigated the role of genetic variants of two SNPs that are candidates to moderate the effects of PNMS on hippocampal volume: COMT (rs4680) and BDNF (rs6265). To investigate this, we assessed 53 children who were in utero during the January 1998 Quebec ice storm. In June 1998 their mothers responded to questionnaires about their objective, cognitive, and subjective levels of stress from the ice storm. When children were 11 1/2 years old, T1-weighted structural magnetic resonance imaging (MRI) scans were obtained using a 3T scanner and analyzed to determine hippocampal volumes. We collected and genotyped the children’s saliva DNA. Moderation analyses were conducted to determine whether either or both of the SNPs moderate the effect of PNMS on hippocampal volumes. We found that objective hardship was associated with right hippocampal volume in girls, and that the BDNF and COMT genotypes were associated with left hippocampal volume in boys and girls. In addition, SNPs located on COMT moderated the effect of maternal objective distress in boys, and subjective distress in girls, on both right hippocampal volume. Thus, we conclude that an individual’s genotype alters their susceptibility to the effects of PNMS.

Highlights

The hippocampus plays a key role in memory formation and learning (Spalding et al, 2013; Voss et al, 2017) and has been involved in spatial mapping and internalizing behaviors, such as anxiety and depression (Engin and Treit, 2007; Gatt et al, 2009; Gujral et al, 2017)
For brain-derived neurotrophic factor (BDNF) genes, there was a trend for the major homozygote (CC) of the BDNF gene to be associated with smaller Left HCV/total intracranial volume (TIV) ratio (r = 0.369, p = 0.058) in boys (Table 4), no significant finding for right hippocampal volume-total intracranial volume ratio (HCV/TIV) ratio was observed
We have found that a SNP located on COMT significantly moderates the effects of Prenatal maternal stress (PNMS) on hippocampal volume, resulting in differential susceptibility between COMT genotypes to the effects of PNMS

Summary

Introduction

The hippocampus plays a key role in memory formation and learning (Spalding et al, 2013; Voss et al, 2017) and has been involved in spatial mapping and internalizing behaviors, such as anxiety and depression (Engin and Treit, 2007; Gatt et al, 2009; Gujral et al, 2017). Prenatal maternal stress (PNMS) is one such factor that has been thoroughly researched for its effects on hippocampal development in animals. These studies have provided substantial evidence that PNMS affects hippocampal development (Charil et al, 2010; Ortega-Martinez, 2015; Grigoryan and Segal, 2016). Magnetic resonance imaging (MRI) scans demonstrate that PNMS is associated with reduced hippocampal volume (Uno et al, 1994; Schmitz et al, 2002; Coe et al, 2003). These studies consistently demonstrate a reduction in hippocampal volume following PNMS, Schmitz et al (2002) report a sexspecific effect, with reduced volume only observed in female rats, while other studies find effects in both sexes

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