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

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

doi:10.3389/fnbeh.2019.00175

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

Front Behav Neurosci. 2019 Aug 6:13:175. doi: 10.3389/fnbeh.2019.00175. eCollection 2019.

Authors

Henriette Acosta¹, Jetro J Tuulari^{1

2

3}, Noora M Scheinin¹, Niloofar Hashempour¹, Olli Rajasilta¹, Tuomas I Lavonius¹, Juho Pelto¹, Virva Saunavaara⁴, Riitta Parkkola⁵, Tuire Lähdesmäki⁶, Linnea Karlsson^{1

7}, Hasse Karlsson^{1

2}

Affiliations

¹ The FinnBrain Birth Cohort Study, Turku Brain and Mind Center, Department of Clinical Medicine, University of Turku, Turku, Finland.
² Department of Psychiatry, Turku University Hospital, University of Turku, Turku, Finland.
³ Turku Collegium for Science and Medicine, University of Turku, Turku, Finland.
⁴ Department of Medical Physics, Turku University Hospital, Turku, Finland.
⁵ Department of Radiology, Turku University Hospital, University of Turku, Turku, Finland.
⁶ Department of Pediatric Neurology, Turku University Hospital, University of Turku, Turku, Finland.
⁷ Department of Child Psychiatry, Turku University Hospital, University of Turku, Turku, Finland.

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.

Keywords: SDQ; VBM; amygdale; behavior; brain; children; development; prenatal stress.