Is maternal prenatal exposure to lithium in drinking water associated with autism spectrum disorder (ASD) in offspring?


Lithium is a naturally occurring and trace element that has mood-stabilizing effects. It has been used for several decades as a treatment for bipolar disorder and depression.

Although the therapeutic use of lithium during pregnancy has been associated with adverse birth outcomes, it is unknown whether exposure to lithium in drinking water affects brain health in early life.

Studies have shown that exposure to lithium during pregnancy can lead to changes in the developing brain of the fetus. Specifically, lithium can interfere with the normal functioning of neurotransmitters, such as serotonin and dopamine, which are crucial for healthy brain development. This disruption can result in alterations in brain structure and function, which can manifest as ASD and other neurodevelopmental disorders.

To avoid the potential negative effects of lithium exposure during pregnancy, it is recommended that women who are planning to become pregnant or who are pregnant avoid taking lithium unless absolutely necessary. If a woman is currently taking lithium for a psychiatric condition, it is important to discuss the risks and benefits of continuing the medication with a healthcare provider.

In addition to potential effects on the developing fetus, lithium can also have negative effects on the brain in adults. Long-term use of Lithium can also have an impact on mood and affect. While lithium is commonly used to treat bipolar disorder and stabilize mood, it can also cause side effects such as lethargy, fatigue, and apathy.

In some cases, these side effects can contribute to depression or a general lack of interest in activities that were previously enjoyable. Therefore, it is important to monitor mood and affect when taking lithium and to report any changes or concerns to a healthcare provider.

One of the primary ways that lithium impacts the brain is by affecting neurotransmitter levels. Specifically, lithium is thought to inhibit the reuptake of serotonin and norepinephrine, two neurotransmitters that are important for regulating mood and emotions. By inhibiting the reuptake of these neurotransmitters, lithium can increase their levels in the brain, leading to a stabilizing effect on mood.

Lithium is also thought to affect the levels of certain other neurotransmitters, including dopamine, glutamate, and GABA. Dopamine is a neurotransmitter that is associated with reward and pleasure, and it is thought that lithium may decrease dopamine levels in the brain. Glutamate is an excitatory neurotransmitter that is important for learning and memory, and lithium may decrease glutamate levels in the brain. GABA is an inhibitory neurotransmitter that is important for regulating anxiety, and lithium may increase GABA levels in the brain.

In addition to affecting neurotransmitter levels, lithium can also affect the structure and function of neurons in the brain. Studies have shown that lithium can increase the density of certain types of neurons in the prefrontal cortex, a region of the brain that is important for executive functions such as decision-making and impulse control. Lithium has also been shown to increase the length and branching of dendrites, the structures on neurons that receive and transmit signals. This may enhance neural plasticity and promote the formation of new neural connections, which can improve cognitive function.

However, there are also negative effects of lithium on the brain. Long-term use of lithium has been associated with changes in brain structure and function, such as decreased gray matter volume and impaired cognitive function. These effects can manifest as memory impairment, confusion, and difficulty with problem-solving. In addition, lithium can also cause side effects such as lethargy, fatigue, and apathy, which can contribute to depression or a general lack of interest in activities that were previously enjoyable.

The objective of this study was to evaluate whether ASD in offspring is associated with maternal exposure to lithium in drinking water during pregnancy.

Methodology: The study was a nationwide population-based case-control study in Denmark that identified 8,442 children diagnosed with ASD born from 2000 through 2013 and 43,864 control participants matched by birth year and sex from the Danish Medical Birth Registry. Geocoded maternal residential addresses during pregnancy were linked to lithium level (range, 0.6 to 30.7 μg/L) in drinking water estimated using kriging interpolation based on 151 waterworks measurements of lithium across all regions in Denmark. The study team estimated odds ratios (ORs) and 95% CIs for ASD according to estimated geocoded maternal exposure to natural source of lithium in drinking water as a continuous (per IQR) or a categorical (quartile) variable, adjusting for sociodemographic factors and ambient air pollutants levels. The study team also conducted stratified analyses by birth years, child’s sex, and urbanicity.

Results: The study found that every IQR increase in estimated geocoded maternal exposure to natural source of lithium in drinking water was associated with higher odds for ASD in offspring (OR, 1.23; 95% CI, 1.17-1.29). Elevated odds among offspring for ASD were estimated starting from the second quartile (7.36 to 12.67 μg/L) of estimated maternal exposure to drinking water with lithium and the OR for the highest quartile (more than 16.78 μg/L) compared with the reference group (less than 7.39 μg/L) was 1.46 (95% CI, 1.35-1.59). The associations were unchanged when adjusting for air pollution exposures and no differences were apparent in stratified analyses.

Conclusion: The study suggests that maternal prenatal exposure to lithium from naturally occurring drinking water sources in Denmark was associated with an increased ASD risk in the offspring. The study’s findings suggest that naturally occurring lithium in drinking water may be a novel environmental risk factor for ASD development that requires further investigation.

Limitations: The study has some limitations, including the possibility of misclassification of exposure due to the use of estimated rather than actual measurements of lithium levels in drinking water. Additionally, the study only assessed exposure to lithium from natural sources and did not account for exposure from other sources, such as medication or dietary intake. Finally, the study was conducted in Denmark, and the findings may not be generalizable to other populations or countries with different drinking water sources and lithium levels.

In summary, the study suggests that maternal prenatal exposure to lithium in drinking water may be associated with an increased risk of ASD in offspring. Further research is needed to confirm these findings and to investigate the underlying mechanisms of this association.

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