Association of cumulative prenatal adversity with infant subcortical structure volumes and child problem behavior and its moderation by a coexpression polygenic risk score of the serotonin system
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Abstract Prenatal adversity has been linked to later psychopathology. Yet, research on cumulative prenatal adversity, as well as its interaction with offspring genotype, on brain and behavioral development is scarce. With this study, we aimed to address this gap. In Finnish mother–infant dyads, we investigated the association of a cumulative prenatal adversity sum score (PRE-AS) with (a) child emotional and behavioral problems assessed with the Strengths and Difficulties Questionnaire at 4 and 5 years (N = 1568, 45.3% female), (b) infant amygdalar and hippocampal volumes (subsample N = 122), and (c) its moderation by a hippocampal-specific coexpression polygenic risk score based on the serotonin transporter (SLC6A4) gene. We found that higher PRE-AS was linked to greater child emotional and behavioral problems at both time points, with partly stronger associations in boys than in girls. Higher PRE-AS was associated with larger bilateral infant amygdalar volumes in girls compared to boys, while no associations were found for hippocampal volumes. Further, hyperactivity/inattention in 4-year-old girls was related to both genotype and PRE-AS, the latter partially mediated by right amygdalar volumes as preliminary evidence suggests. Our study is the first to demonstrate a dose-dependent sexually dimorphic relationship between cumulative prenatal adversity and infant amygdalar volumes.
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Maternal smoking and alcohol exposure during pregnancy are associated with increased ADHD risk, likely through neurotoxic effects on fetal development.
“Maternal smoking [61] and alcohol exposure [62] during pregnancy are associated with increased ADHD risk, likely through neurotoxic effects on fetal development.”
From ADHD in Adulthood: Clinical Presentation, Comorbidities, and Treatment Perspectives (2025) · cites this paper as [61]
The Discussion (page unavailable) says maternal smoking is among prenatal factors associated with ADHD, but cautions that the evidence is inconclusive and no causal link has been established. The paper does not specifically link prenatal alcohol exposure to ADHD or establish neurotoxic effects on fetal development as the mechanism. (LLM, conf=0.84)
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Self-citationTuulari, J. J., Kataja, E., Leppänen, J. M., Lewis, J. D., Nolvi, S., Häikiö, T., Lehtola, S. J., Hashempour, N., Saunavaara, J. P., Scheinin, N. M., et al. (2020) · Developmental Cognitive Neuroscience · doi:10.1016/j.dcn.2020.100839 · Cited by 19 · see citing works
Self-citationLi, T., Franke, B., AriasVasquez, A., & Mota, N. (2020) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32828 · Cited by 14 · see citing works
Neonatal amygdala volumes and the development of self-regulation from early infancy to toddlerhood.
Nolvi, S., Tuulari, J. J., Pelto, J., Bridgett, D. J., Eskola, E., Lehtola, S. J., Hashempour, N., Korja, R., Kataja, E., Saunavaara, J. P., et al. (2021) · Neuropsychology · doi:10.1037/neu0000724 · Cited by 14 · see citing works
Self-citationPrenatal Risk Predicts Preschooler Executive Function: A Cascade Model
Camerota, M., & Willoughby, M. T. (2019) · Child Development · doi:10.1111/cdev.13271 · Cited by 13 · see citing works
Wade, M., Madigan, S. L., Akbari, E. M., & Jenkins, J. M. (2015) · Frontiers in Psychology · doi:10.3389/fpsyg.2015.00354 · Cited by 12 · see citing works
Sex differences in the vulnerability of the hippocampus to prenatal stress
Soti, M., Ranjbar, H., Kohlmeier, K. A., & Shabani, M. (2022) · Developmental Psychobiology · doi:10.1002/dev.22305 · Cited by 10 · see citing works
Influence of Birth Weight on Internalizing Traits Modulated by Serotonergic Genes
Broekman, B. F. P., Chan, Y. H., Goh, L. K., Fung, D. S. S., Gluckman, P. D., Saw, S., & Meaney, M. J. (2011) · PEDIATRICS · doi:10.1542/peds.2010-3714 · Cited by 9 · see citing works
Flagged first, then by citations
2 of the 97 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Gluckman, P. D., & Hanson, M. A. (2006). The developmental origins of health and disease: An overview. In P. Gluckman, & M. A. Hanson (Eds.), Developmental origins of health and disease (pp. 1-4). Cambridge University Press.
- Yilmazer-Hanke, D. M. (2012). Amygdala. In J. K. Mai, & G. Paxinos (Eds.), The human nervous system (3rd ed., pp. 759-834). Academic Press.
Cited by
Sorted by citations
The effect of prenatal maternal distress on offspring brain development: A systematic review
Mandl, S., Alexopoulos, J., Doering, S., Wildner, B., Seidl, R., & Bartha, L. (2024) · Early Human Development · doi:10.1016/j.earlhumdev.2024.106009 · Cited by 34 · see citing works
ADHD in Adulthood: Clinical Presentation, Comorbidities, and Treatment Perspectives
Bogdańska-Chomczyk, E., Majewski, M. K., & Kozłowska, A. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262211020 · Cited by 15 · see citing works
“Maternal smoking [61] and alcohol exposure [62] during pregnancy are associated with increased ADHD risk, likely through neurotoxic effects on fetal development.”
Illius, S., Eder, J., Vogel, S., & Alexander, N. (2026) · Translational Psychiatry · doi:10.1038/s41398-025-03793-7 · Cited by 4 · see citing works
Creasey, N., Schuurmans, I. K., Tsotsi, S., Defina, S., Baltramonaityte, V., Felix, J. F., Neumann, A., Page, C. M., Tollenaar, M. S., Bekkhus, M., et al. (2025) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2025.107388 · Cited by 3 · see citing works
López‐Morales, H., Sosa, J. M., Zamora, E. V., del Valle, M. V., Aguilar, M. J., Trudo, R. G., Cánepa, E. T., López, M., Faas, A. E., & Urquijo, S. (2026) · Infant Mental Health Journal · doi:10.1002/imhj.70061 · Cited by 2 · see citing works
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Temporal Associations Between Human Milk Metabolites and the Infant Gut Microbiome and metabolomePreprint
Isokääntä, H., Perasto, L., Lamichhane, S., Ovaska, M., Kallonen, T., Munukka, E., Kråkström, M., Karlsson, H., Karlsson, L., Kailanto, H.-M., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.28.681130 · Cited by 1 · see citing works
Self-citationStructural brain differences in school-aged children who are HIV-exposed uninfected
Forster, E. A., Syed, B., Bowes, J., Young, J., Kapoor, C., Head, M., Lerch, J. P., Miller, E., Brophy, J. C., Bitnun, A., et al. (2025) · BMC Medicine · doi:10.1186/s12916-025-04332-3
Perinatal Risk Factors Associated With Infant Socioemotional Development
Mirhashem, R., Bernard, K., Lobel, M., Mahaffey, B., & Preis, H. (2026) · Infant and Child Development · doi:10.1002/icd.70095
Cima, M., Oosterling, M., Loheide‐Niesmann, L., Meulenbeek, K., Spagnuolo, F., Tonnaer, F., Frankenberger, L., Riem, M. M. E., & Thijssen, S. (2026) · Aggression and Violent Behavior · doi:10.1016/j.avb.2026.102158
López‐Morales, H., Sosa, J. M., Cánepa, E. T., Schrott, G. D., Faas, A. E., López, M., & Urquijo, S. (2026) · Research Square · doi:10.21203/rs.3.rs-9180794/v1
- Authors
- Acosta, H., Kantojärvi, K., Tuulari, J. J., Lewis, J. D., Hashempour, N., Scheinin, N. M., Lehtola, S. J., Nolvi, S., Fonov, V. S., Collins, D. L., Evans, A. C., Parkkola, R., Lähdesmäki, T., Saunavaara, J., Merisaari, H., Karlsson, L., Paunio, T., & Karlsson, H.
- Affiliations
- University of Turku (FI)
- University of Helsinki (FI)
- McGill University (CA)
- Turku University Hospital (FI)
- Corresponding author
- Acosta, Henriette
- ORCID
- Venue
- Development and Psychopathology
- Publisher
- Cambridge University Press (CUP)
- Published
- 2023-04-03
- Volume
- 36
- Issue
- 3
- Pages
- 1027-1042
- ISSN
- 0954-5794 (ISSN-L)
- 1469-2198
- OpenAlex
- W4362506348
- Cited by
- 11
- References
- 97
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 2
- FWCI
- 2.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Development and Psychopathology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UTUPub (University of Turku) (submittedVersion)
- Työväentutkimus Vuosikirja (submittedVersion)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- Funders
- Alfred Kordelinin Säätiö
- Fondation Brain Canada
- National Alliance for Research on Schizophrenia and Depression
- Yrjö Jahnssonin Säätiö (P3498, P3654)
- Compute Canada
- Academy of Finland (#308176, 1350941, PROFI5, 264363, #325292, #26080983, #253270, 134950, #253346, 264363, 253270, 134950)
- Jane ja Aatos Erkon Säätiö
- Juho Vainion Säätiö
- Signe ja Ane Gyllenbergin Säätiö (P3654, 325292, 308176)
- Emil Aaltosen Säätiö
- Lastentautien Tutkimussäätiö
- Sigrid Juséliuksen Säätiö
- Varsinais-Suomen Sairaanhoitopiiri
- Turun Yliopistosäätiö
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Keywords
- hippocampal volume, child emotional and behavioral problems, hyperactivity/inattention, serotonin transporter, serotonergic system, sex differences, prenatal stress, brain development, mother-infant dyads, mediation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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