Subcortical brain volumes in young infants exposed to antenatal maternal depression: Findings from a South African birth cohort

doi:10.1016/j.nicl.2022.103206

. 2022:36:103206.

doi: 10.1016/j.nicl.2022.103206. Epub 2022 Sep 19.

Subcortical brain volumes in young infants exposed to antenatal maternal depression: Findings from a South African birth cohort

Affiliations

¹ Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa; South African Medical Research Council (SA-MRC) Unit on Child & Adolescent Health, University of Cape Town, Cape Town, South Africa; Department of Psychiatry & Mental Health, University of Cape Town, Cape Town, South Africa; The Neuroscience Institute, University of Cape Town, Cape Town, South Africa. Electronic address: nynke.groenewold@uct.ac.za.
² Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa; The Neuroscience Institute, University of Cape Town, Cape Town, South Africa; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, United Kingdom.
³ Department of Behavioral and Social Sciences and International Health Institute, Brown University School of Public Health, Providence, RI, USA; Division of Epidemiology and Biostatistics, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.
⁴ Department of Psychiatry & Mental Health, University of Cape Town, Cape Town, South Africa; The Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
⁵ Department of Psychiatry & Mental Health, University of Cape Town, Cape Town, South Africa.
⁶ Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa; The Neuroscience Institute, University of Cape Town, Cape Town, South Africa; SA-MRC Unit on Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa.
⁷ Departments of Neurology, Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, USA.
⁸ Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa; South African Medical Research Council (SA-MRC) Unit on Child & Adolescent Health, University of Cape Town, Cape Town, South Africa.
⁹ Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa; The Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
¹⁰ Department of Psychiatry & Mental Health, University of Cape Town, Cape Town, South Africa; The Neuroscience Institute, University of Cape Town, Cape Town, South Africa; SA-MRC Unit on Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa.

PMID: 36162238
PMCID: PMC9668606
DOI: 10.1016/j.nicl.2022.103206

Subcortical brain volumes in young infants exposed to antenatal maternal depression: Findings from a South African birth cohort

Nynke A Groenewold et al. Neuroimage Clin. 2022.

. 2022:36:103206.

doi: 10.1016/j.nicl.2022.103206. Epub 2022 Sep 19.

Authors

Affiliations

¹ Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa; South African Medical Research Council (SA-MRC) Unit on Child & Adolescent Health, University of Cape Town, Cape Town, South Africa; Department of Psychiatry & Mental Health, University of Cape Town, Cape Town, South Africa; The Neuroscience Institute, University of Cape Town, Cape Town, South Africa. Electronic address: nynke.groenewold@uct.ac.za.
² Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa; The Neuroscience Institute, University of Cape Town, Cape Town, South Africa; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, United Kingdom.
³ Department of Behavioral and Social Sciences and International Health Institute, Brown University School of Public Health, Providence, RI, USA; Division of Epidemiology and Biostatistics, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.
⁴ Department of Psychiatry & Mental Health, University of Cape Town, Cape Town, South Africa; The Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
⁵ Department of Psychiatry & Mental Health, University of Cape Town, Cape Town, South Africa.
⁶ Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa; The Neuroscience Institute, University of Cape Town, Cape Town, South Africa; SA-MRC Unit on Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa.
⁷ Departments of Neurology, Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, USA.
⁸ Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa; South African Medical Research Council (SA-MRC) Unit on Child & Adolescent Health, University of Cape Town, Cape Town, South Africa.
⁹ Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa; The Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
¹⁰ Department of Psychiatry & Mental Health, University of Cape Town, Cape Town, South Africa; The Neuroscience Institute, University of Cape Town, Cape Town, South Africa; SA-MRC Unit on Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa.

PMID: 36162238
PMCID: PMC9668606
DOI: 10.1016/j.nicl.2022.103206

Abstract

Background: Several studies have reported enlarged amygdala and smaller hippocampus volumes in children and adolescents exposed to maternal depression. It is unclear whether similar volumetric differences are detectable in the infants' first weeks of life, following exposure in utero. We investigated subcortical volumes in 2-to-6 week old infants exposed to antenatal maternal depression (AMD) from a South African birth cohort.

Methods: AMD was measured with the Beck Depression Inventory 2nd edition (BDI-II) at 28-32 weeks gestation. T2-weighted structural images were acquired during natural sleep on a 3T Siemens Allegra scanner. Subcortical regions were segmented based on the University of North Carolina neonatal brain atlas. Volumetric estimates were compared between AMD-exposed (BDI-II ⩾ 20) and unexposed (BDI-II < 14) infants, adjusted for age, sex and total intracranial volume using analysis of covariance.

Results: Larger volumes were observed in AMD-exposed (N = 49) compared to unexposed infants (N = 75) for the right amygdala (1.93% difference, p = 0.039) and bilateral caudate nucleus (left: 5.79% difference, p = 0.001; right: 6.09% difference, p < 0.001). A significant AMD-by-sex interaction was found for the hippocampus (left: F(1,118) = 4.80, p = 0.030; right: F(1,118) = 5.16, p = 0.025), reflecting greater volume in AMD-exposed females (left: 5.09% difference, p = 0.001, right: 3.54% difference, p = 0.010), but not males.

Conclusions: Volumetric differences in subcortical regions can be detected in AMD-exposed infants soon after birth, suggesting structural changes may occur in utero. Female infants might exhibit volumetric changes that are not observed in male infants. The potential mechanisms underlying these early volumetric differences, and their significance for long-term child mental health, require further investigation.

Keywords: Brain morphometry; Child development; Depressive disorders; Magnetic resonance imaging; Prenatal stress; Sex differences.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

**Fig. 1**
Drakenstein Child Health Study flowchart for the subsample of 2–6 weeks old infants with and without antenatal maternal depression (AMD) exposure that underwent brain magnetic resonance (MR) imaging. BDI = Beck Depression Inventory, 2nd edition; HIV = Human Immodeficiency Virus.

**Fig. 2**
Percentage mean difference in grey matter volume for the subcortical regions that showed significant differences between AMD-exposed and AMD-unexposed infants* after adjusting for infant age, sex and intracranial volume, visualized in a neonate template brain. * The subcortical regions that did not show a significant group difference in volume are included for anatomical reference, in pale grey.

**Fig. 3**
Differences in hippocampus and amygdala volume related to AMD exposure presented separately for female and male infants. # Subcortical region with a significant AMD-by-sex interaction (p < 0.05) * Significant difference between AMD-exposed and AMD-unexposed female infants (p < 0.05) ** Significant difference between AMD-exposed and AMD-unexposed female infants (p < 0.01).

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References

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1. Acosta H., Kantojarvi K., Tuulari J.J., Lewis J.D., Hashempour N., Scheinin N.M., Lehtola S.J., Fonov V.S., Collins D.L., Evans A., Parkkola R., Lahdesmaki T., Saunavaara J., Merisaari H., Karlsson L., Paunio T., Karlsson H. Sex-specific association between infant caudate volumes and a polygenic risk score for major depressive disorder. J. Neurosci. Res. 2020;98:2529–2540. - PubMed
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[1] Acosta H., Tuulari J.J., Scheinin N.M., Hashempour N., Rajasilta O., Lavonius T.I., Pelto J., Saunavaara V., Parkkola R., Lahdesmaki T., Karlsson L., Karlsson H. Prenatal maternal depressive symptoms are associated with smaller amygdalar volumes of four-year-old children. Psychiatry Research-Neuroimaging. 2020;304 - PubMed

[2] Acosta H., Tuulari J.J., Scheinin N.M., Hashempour N., Rajasilta O., Lavonius T.I., Pelto J., Saunavaara V., Parkkola R., Lahdesmaki T., Karlsson L., Karlsson H. Prenatal maternal depressive symptoms are associated with smaller amygdalar volumes of four-year-old children. Psychiatry Research-Neuroimaging. 2020;304 - PubMed

[3] Acosta H., Kantojarvi K., Hashempour N., Pelto J., Scheinin N.M., Lehtola S.J., Lewis J.D., Fonov V.S., Collins D.L., Evans A., Parkkola R., Lahdesmaki T., Saunavaara J., Karlsson L., Merisaari H., Paunio T., Karlsson H., Tuulari J.J. Partial support for an interaction between a polygenic risk score for major depressive disorder and prenatal maternal depressive symptoms on infant right amygdalar volumes. Cereb. Cortex. 2020;30:6121–6134. - PubMed

[4] Acosta H., Kantojarvi K., Hashempour N., Pelto J., Scheinin N.M., Lehtola S.J., Lewis J.D., Fonov V.S., Collins D.L., Evans A., Parkkola R., Lahdesmaki T., Saunavaara J., Karlsson L., Merisaari H., Paunio T., Karlsson H., Tuulari J.J. Partial support for an interaction between a polygenic risk score for major depressive disorder and prenatal maternal depressive symptoms on infant right amygdalar volumes. Cereb. Cortex. 2020;30:6121–6134. - PubMed

[5] Acosta H., Kantojarvi K., Tuulari J.J., Lewis J.D., Hashempour N., Scheinin N.M., Lehtola S.J., Fonov V.S., Collins D.L., Evans A., Parkkola R., Lahdesmaki T., Saunavaara J., Merisaari H., Karlsson L., Paunio T., Karlsson H. Sex-specific association between infant caudate volumes and a polygenic risk score for major depressive disorder. J. Neurosci. Res. 2020;98:2529–2540. - PubMed

[6] Acosta H., Kantojarvi K., Tuulari J.J., Lewis J.D., Hashempour N., Scheinin N.M., Lehtola S.J., Fonov V.S., Collins D.L., Evans A., Parkkola R., Lahdesmaki T., Saunavaara J., Merisaari H., Karlsson L., Paunio T., Karlsson H. Sex-specific association between infant caudate volumes and a polygenic risk score for major depressive disorder. J. Neurosci. Res. 2020;98:2529–2540. - PubMed

[7] Adamson B., Letourneau N., Lebel C. Prenatal maternal anxiety and children's brain structure and function: A systematic review of neuroimaging studies. J. Affect. Disord. 2018;241:117–126. - PubMed

[8] Adamson B., Letourneau N., Lebel C. Prenatal maternal anxiety and children's brain structure and function: A systematic review of neuroimaging studies. J. Affect. Disord. 2018;241:117–126. - PubMed

[9] Andersen S. Trajectories of brain development: point of vulnerability or window of opportunity? Neurosci. Biobehav. Rev. 2003;27:3–18. - PubMed

[10] Andersen S. Trajectories of brain development: point of vulnerability or window of opportunity? Neurosci. Biobehav. Rev. 2003;27:3–18. - PubMed

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Subcortical brain volumes in young infants exposed to antenatal maternal depression: Findings from a South African birth cohort

Affiliations

Subcortical brain volumes in young infants exposed to antenatal maternal depression: Findings from a South African birth cohort

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Abstract

Conflict of interest statement

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