Maternal Pregnancy-Related Anxiety Is Associated With Sexually Dimorphic Alterations in Amygdala Volume in 4-Year-Old Children.

Henriette Acosta,Juho Pelto,Virva Saunavaara,Tuire Lähdesmäki,Jetro J Tuulari,Niloofar Hashempour,Olli Rajasilta,Hasse Karlsson,Noora M Scheinin,Linnea Karlsson,Tuomas I Lavonius,Riitta Parkkola

doi:10.3389/fnbeh.2019.00175

Henriette Acosta, Juho Pelto + Show 10 more

Open Access

https://doi.org/10.3389/fnbeh.2019.00175

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Abstract

Prenatal stress is associated with child behavioral outcomes increasing susceptibility for psychiatric disorders in later life. Altered fetal brain development might partly mediate this association, as some studies suggest. With this study, we investigated the relation between prenatal stress, child’s brain structure and behavioral problems. The association between self-reported maternal pregnancy-related anxiety (PRAQ-R2 questionnaire, second and third trimester) and brain gray matter volume was probed in 27 4-year-old children (13 female). Voxel based morphometry was applied with an age-matched template in SPM for the whole-brain analyses, and amygdala volume was assessed with manual segmentation. Possible pre- and postnatal confounders, such as maternal depression and anxiety among others, were controlled for. Child behavioral problems were assessed with the Strength and Difficulties Questionnaire by maternal report. We found a significant interaction effect of pregnancy-related anxiety and child’s sex on child’s amygdala volume, i.e., higher pregnancy-related anxiety in the second trimester was related to significantly greater left relative amygdala volume in girls compared to boys. Further exploratory analyses yielded that both maternal pregnancy-related anxiety and child’s amygdala volume are related to child emotional and behavioral difficulties: While higher pregnancy-related anxiety was associated with more emotional symptoms, peer relationship problems and overall child difficulties, greater left amygdala volume was related to less of these child difficulties and might partly mediate sex-specific associations between pregnancy-related anxiety and child behavioral difficulties. Our data suggest that maternal prenatal distress leads to sexually dimorphic structural changes in the offspring’s limbic system and that these changes are also linked to behavioral difficulties. Our results provide further support for the notion that prenatal stress impacts child development.

Highlights

Child development is shaped by genetic, and by environmental factors (Greenough et al, 1987; Rice et al, 2010)
In post hoc analyses we investigated the association between amygdala volumes and PRAQ scores in semipartial correlation analyses, in the whole sample and in boys and girls separately
Analyzing Sex Differences, Higher PRAQ Scores of the Second Trimester Were Significantly Associated With Smaller Left Amygdala Volumes in Boys Compared to Girls In a second step, we investigated in multiple linear regression analyses whether the association between amygdala volumes and the individual PRAQ scores significantly differs between girls and boys (Table 3)

Summary

Introduction

Child development is shaped by genetic, and by environmental factors (Greenough et al, 1987; Rice et al, 2010). According to the theory of “developmental origins of health and disease,” environmental factors during development can have long-lasting programing effects on individual health and disease susceptibility (Gluckman and Hanson, 2006; Wadhwa et al, 2009; Moog et al, 2017; O’Donnell and Meaney, 2017). The intrauterine period of life constitutes a sensitive time window due to the rapid development of the embryonic/fetal organism. Risk factors related to maternal health and behavior, such as maternal psychological distress or exposure to stressful life events, that affect intrauterine development, have been established. Several studies have shown that maternal distress during pregnancy shapes behavioral, neurodevelopmental and other health-related outcomes of the offspring over the lifespan. Higher self-reported maternal prenatal distress was associated with more fearfulness (Henrichs et al, 2009; Nolvi et al, 2016) and higher negative affectivity (Blair et al, 2011) of infants, with emotional and behavioral problems of children (O’Connor et al, 2002, 2003; O’Donnell et al, 2014), and anxiety disorders of young adults (Capron et al, 2015) (for a review see e.g., Bock et al, 2015; Entringer et al, 2015; O’Donnell and Meaney, 2017)

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