For many women with bipolar disorder, lithium is an effective mood stabilizer. While many studies have explored the teratogenic effects of lithium, there is currently very limited information on the longer term effects of prenatal lithium exposure on children’s neurodevelopment. In a recent study, Poels and colleagues from the Erasmus University Medical Center in the Netherlands have used neuroimaging to better understand the effects of prenatal lithium exposure on the developing brain.  

This study included 63 children born to women with a diagnosis of bipolar spectrum disorder: 30 with and 33 without prenatal exposure to lithium. Participants were evaluated at 8 to 13 years of age using structural MRI and diffusion tensor imaging in order to assess global brain volume and white matter integrity. As comparison data from the general population, the researchers used brain imaging from participants in the Generation R study (N = 3243).

In comparing lithium-exposed to non-exposed children born to mothers with bipolar disorder, this study found no statistically significant associations between prenatal lithium exposure and structural brain measures, although there was a non-significant trend toward reduced subcortical gray matter volume. When they compared lithium-exposed children to those in the general population, lithium-exposed children showed reduced subcortical gray and cortical white matter volumes.

This is the first study to investigate the influence of prenatal lithium exposure on brain structure in children using neuroimaging. Although small in size, the study provides reassuring data, observing no statistically significant associations between lithium exposure during pregnancy and brain structure or global white matter integrity. There was a small — but statistically non-significant — reduction in subcortical gray matter volume in children with prenatal lithium exposure.

The strength of this study is that the primary comparison group consisted of lithium-unexposed children born to mothers with bipolar disorder. This comparison helps to minimize some of the differences between the exposed and unexposed children that may be related to psychiatric illness in the mother. This, however, does not eliminate all the differences; mothers taking lithium during pregnancy had earlier onset of illness and more lifetime episodes, and were more likely to have lower household income and less education. Thus, we cannot rule out the contribution of illness severity and associated demographic factors to the outcomes observed in this study.

Underscoring the importance of a carefully selected control group is the finding that, when compared to children in the general population, the researchers observed differences in brain structure between lithium-exposed and non-exposed children born to mothers with bipolar disorder and children in the general population cohort. These differences may be related to genetic variables, family environment, or unmeasured exposures during pregnancy. 

The findings of the current study align with previous studies of neuropsychological functioning. In an earlier study carried out in the same cohort, Poels and colleagues (2021) compared 56 lithium-exposed children to 43 non-lithium-exposed children from mothers with a bipolar spectrum disorder using validated neuropsychological tests (NEPSY-II-NL and SON-R 6–40) to assess IQ and six different neuropsychological domains: attention and executive functioning, social perception, memory and learning, sensorimotor, visuospatial processing and language. Overall, they found no statistically significant association between prenatal lithium exposure and IQ or neuropsychological functioning.

Ruta Nonacs, MD PhD

Poels EMP, Kamperman AM, Bijma HH, Honig A, van Kamp IL, Kushner SA, Hoogendijk WJG, Bergink V, White T. Brain development after intrauterine exposure to lithium: A magnetic resonance imaging study in school-age children.  Bipolar Disord. 2023 Jan 12. Poels EMP, Schrijver L, White TJH, et al. The effect of prenatal lithium exposure on the neuropsychological development of the child. Bipolar Disord. 2021; 24:310-319.

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