Brain development after intrauterine exposure to lithium: A magnetic resonance imaging study in school-age children

Eline M.P. Poels*, Astrid M. Kamperman, Hilmar H. Bijma, Adriaan Honig, Inge L. van Kamp, Steven A. Kushner, Witte J.G. Hoogendijk, Veerle Bergink, Tonya White

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)
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Objective: Lithium is often continued during pregnancy to reduce the risk of perinatal mood episodes for women with bipolar disorder. However, little is known about the effect of intrauterine lithium exposure on brain development. The aim of this study was to investigate brain structure in children after intrauterine exposure to lithium. Methods: Participants were offspring, aged 8–14 years, of women with a diagnosis of bipolar spectrum disorder. In total, 63 children participated in the study: 30 with and 33 without intrauterine exposure to lithium. Global brain volume outcomes and white matter integrity were assessed using structural MRI and diffusion tensor imaging, respectively. Primary outcomes were total brain, cortical and subcortical gray matter, cortical white matter, lateral ventricles, cerebellum, hippocampus and amygdala volumes, cortical thickness, cortical surface area and global fractional anisotropy, and mean diffusivity. To assess how our data compared to the general population, global brain volumes were compared to data from the Generation R study (N = 3243). Results: In our primary analyses, we found no statistically significant associations between intrauterine exposure to lithium and structural brain measures. There was a non-significant trend toward reduced subcortical gray matter volume. Compared to the general population, lithium-exposed children showed reduced subcortical gray and cortical white matter volumes. Conclusion: We found no differences in brain structure between lithium-exposed and non-lithium-exposed children aged 8–14 years following correction for multiple testing. While a rare population to study, future and likely multi-site studies with larger datasets are required to validate and extend these initial findings.

Original languageEnglish
Pages (from-to)181-190
Number of pages10
JournalBipolar Disorders
Issue number3
Early online date12 Jan 2023
Publication statusPublished - May 2023

Bibliographical note

Funding Information:
The authors would like to thank all the children and parents who participated in this study. Additionally, the authors are grateful to Ayuk Bakia, Manal Aziz, Ayse Acar-Aydin, and volunteers for the assistance in the data collection.

Publisher Copyright:
© 2023 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.


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