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

Autism is a heterogeneous neurodevelopmental condition arising from complex interactions between genetic susceptibility and environmental factors. Lithium, a naturally occurring element used therapeutically for bipolar disorder and present in food and drinking water, warrants careful evaluation because it readily crosses the placenta and modulates biological pathways critical for brain development. We conducted a structured literature review of PubMed, Embase, and Web of Science through February 20, 2026, and identified 72 human, animal, and in vitro studies examining lithium exposure in relation to autism or neurodevelopmental outcomes. Epidemiologic evidence remains limited, with few studies directly assessing prenatal exposure and insufficient evidence to establish environmental lithium exposure as a neurodevelopmental risk factor. Most human clinical studies reflect therapeutic contexts and demonstrate the mood-stabilizing effects of lithium, whereas human biomarker and experimental studies provide evidence for modulation of glycogen synthase kinase-3β (GSK3β) signaling and thyroid function. Experimental studies indicate that lithium can normalize disease-associated phenotypes in autism-relevant models, yet it also induces behavioral and neurological alterations in non-mutant control models, particularly following high-dose or prenatal exposure. Across evidence streams, convergent findings implicate phosphatidylinositol-calcium signaling, GSK3β-dependent pathways, glutamatergic synapse function, and thyroid hormone regulation, supporting the biological plausibility of lithium-related neurodevelopmental effects. Overall, lithium-associated neurodevelopmental effects appear dose-, context-, and timing-dependent. Knowledge gaps remain regarding environmentally relevant prenatal exposures and long-term neurodevelopmental outcomes, underscoring the need for rigorous epidemiologic and mechanistic studies incorporating refined exposure assessment, developmental timing, and genetic susceptibility.