Developmental lithium exposure and neurodevelopment: Epidemiological evidence, biological pathways, and implications...

Area of Science:

• Neurodevelopmental science
• Environmental toxicology
• Pharmacology

Background:

• Autism spectrum disorder (ASD) is a complex neurodevelopmental condition influenced by genetic and environmental factors.
• Lithium, a mood stabilizer, is present in the environment and crosses the placenta, necessitating investigation into its neurodevelopmental effects.
• Existing research on lithium and neurodevelopment is fragmented, requiring a comprehensive review.

Purpose of the Study:

• To systematically review existing literature on lithium exposure and its association with autism and other neurodevelopmental outcomes.
• To evaluate the biological plausibility of lithium's effects on brain development.
• To identify knowledge gaps and guide future research directions.

Main Methods:

• A structured literature review of PubMed, Embase, and Web of Science databases was performed.
• Studies included human, animal, and in vitro research examining lithium exposure and neurodevelopmental outcomes.
• The review considered evidence up to February 20, 2026, identifying 72 relevant studies.

Main Results:

• Epidemiologic evidence directly linking environmental lithium exposure to neurodevelopmental risk is limited.
• Human clinical studies primarily show lithium's mood-stabilizing effects.
• Experimental and biomarker studies suggest lithium modulates GSK3β signaling, thyroid function, and phosphatidylinositol-calcium signaling, with context- and dose-dependent effects on neurodevelopmental models.

Conclusions:

• Lithium's impact on neurodevelopment is biologically plausible, affecting key pathways like GSK3β signaling and thyroid regulation.
• Lithium's effects are dependent on dose, timing, and context, with potential for both normalization of disease phenotypes and induction of alterations in control models.
• Further research is needed on environmentally relevant prenatal exposures and long-term outcomes, emphasizing refined exposure assessment and developmental timing.